Cardiology News

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

WASHINGTON – Patients with heart failure who received an annual influenza vaccine for 3 years running had significantly fewer all-cause hospitalizations and significantly fewer cases of pneumonia during that time, compared with placebo-treated patients with heart failure, in a prospective, randomized, global trial with 5,129 participants.

Although the results failed to show a significant reduction in all-cause deaths linked to influenza vaccination, compared with controls during the entire 3 years of the study, the results did show a significant 21% relative mortality-risk reduction by vaccination during periods of peak influenza circulation, and a significant 23% reduction in cardiovascular deaths, compared with controls during peak seasons.

courtesy Dr. Mark Loeb

“This is the first randomized, controlled trial of influenza vaccine in patients with heart failure, and we showed that vaccination reduces deaths” during peak influenza seasons, Mark Loeb, MD, said during a press briefing at the annual scientific sessions of the American College of Cardiology. The results send “an important global message that patients with heart failure should receive the influenza vaccine,” said Dr. Loeb, a professor at McMaster University, Hamilton, Ont., who specializes in clinical epidemiology and infectious diseases.

Dr. Loeb admitted that he and his associates erred when they picked the time window to assess the two primary endpoints for the trial: the combined rate of cardiovascular death, nonfatal MI, and nonfatal stroke, and this combined endpoint plus hospitalizations for heart failure.

The time window they selected was the entirety of all 3 years following three annual immunizations. That was a mistake.
 

No flu vaccine benefit outside flu season

“We know that the influenza vaccine will not have any effect outside of when influenza is circulating. In retrospect, we should have done that,” Dr. Loeb bemoaned during his talk. He chalked up the bad choice to concern over collecting enough endpoints to see a significant between-group difference when the researchers designed the study.

For the entire 3 years of follow-up, influenza vaccination was tied to a nonsignificant 7% relative risk reduction for the first primary endpoint, and a nonsignificant 9% relative risk reduction for the second primary endpoint, he reported.

But Dr. Loeb lobbied for the relevance of several significant secondary endpoints that collectively showed a compelling pattern of benefit during his talk. These included, for the full 3-years of follow-up, important, significant reductions relative to placebo of 16% for first all-cause hospitalizations (P = .01), and a 42% relative risk reduction in first cases of pneumonia (P = .0006).

Then there were the benefits that appeared during influenza season. In that analysis, first events for the first primary endpoint fell after vaccination by a significant 18% relative to placebo. The in-season analysis also showed the significant cuts in both all-cause and cardiovascular deaths.

Despite the neutral primary endpoints, “if you look at these data as a whole I think they speak to the importance of vaccinating patients with heart failure against influenza,” Dr. Loeb maintained.



‘Totality of evidence supports vaccination’

“I agree that the totality of evidence supports influenza vaccination,” commented Mark H. Drazner, MD, professor and clinical chief of cardiology at the University of Texas Southwestern Medical Center, Dallas, who was designated discussant for the report.

“The message should be to offer influenza vaccine to patients with heart failure,” Dr. Drazner said in an interview. “Previous data on influenza vaccine in patients with heart failure were largely observational. This was a randomized, prospective, placebo-controlled trial. That’s a step forward. Proving efficacy in a randomized trial is important.”

Dr Drazner added that his institution already promotes a “strong mandate” to vaccinate patients with heart failure against influenza.

“The influenza vaccine is a very effective and cost-efficient public health measure. Preventing hospitalizations of patients with heart failure has so many benefits,” commented Craig Beavers, PharmD, vice president of professional services at Baptist Health in Paducah, Ky., and a discussant during the press briefing.

Mitchel L. Zoler/MDedge News

The Influenza Vaccine To Prevent Adverse Vascular Events (IVVE) trial enrolled people with heart failure in New York Heart Association functional class II, III, or IV from any of 10 low- and middle-income countries including China, India, the Philippines, and multiple countries from Africa and the Middle East. They averaged 57 years of age, and slightly more than half were women.

IVVE was sponsored by McMaster University; the only commercial support that IVVE received was a free supply of influenza vaccine from Sanofi Pasteur. Dr. Loeb, Dr. Drazner, and Dr. Beavers had no disclosures.

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

A version of this article first appeared on Medscape.com.

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

A version of this article first appeared on Medscape.com.

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

A version of this article first appeared on Medscape.com.

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

When the PCSK9 inhibitor alirocumab is added to high-intensity statins soon after an acute myocardial infarction (AMI), the reduction in atheroma volume is doubled at 12 months, compared with placebo, while other key signs of plaque stabilization, such as fibrous cap thickness, are also significantly and substantially improved, according to the results of the PACMAN-AMI trial.

The study is consistent with other PCSK9 inhibitor trials, supporting the concept that “we should be seeking very low levels of LDL-C in high-risk patients,” reported Lorenz Räber, MD, PhD, of Bern (Switz.) University Hospital, at the annual scientific sessions of the American College of Cardiology.

Catherine Hackett/MDedge News

Primary outcome was atheroma volume

The primary endpoint was atheroma volume as determined by intravenous ultrasound (IVUS), but the secondary endpoints of maximum lipid core burden, as determined by near infrared spectroscopy (NIRS), and fibrous cap thickness, as determined by optical coherence tomography (OCT), were also adequately powered, according to Dr. Räber.

The imaging measures taken at baseline were repeated in exactly the same spot after 52 weeks on treatment.

For the primary outcome of atheroma volume, the mean 2.1% reduction among those randomized to alirocumab was more than double the 0.9% reduction in the placebo group (P = .001).

The mean reduction in lipid core volume based on a maximum lipid core burden index was also more than doubled (-79.42 vs. -37.60 maxLCBI­4mm; P = .006). The increase in fibrous cap thickness was not quite twofold greater but very close (62.67 vs. 33.19 mcm; P = .001).

From baseline, the relative reductions in LDL-C, which were reached about 4 weeks after starting treatment and maintained over the course of the study, were greater in the group randomized to alirocumab (-84.8% vs. -50.7%). This was expected, but the more important finding was a near linear relationship between reductions of LDL-C and each of these endpoints regardless of treatment, fully explaining the advantage of alirocumab, according to Dr. Räber.

For the addition of alirocumab, “these findings indicate incremental coronary plaque regression, lipid core reduction, and plaque stabilization, and provide a mechanistic rationale in favor of early initiation of very intensive LDL-C lower in the setting of an acute MI,” he said.

The results of the PACMAN-AMI trial were published simultaneously at the time of the ACC presentation.
 

Results consistent with earlier trials

Alirocumab was well tolerated. Injection site reactions (6.1% vs. 3.3%) and general allergic reactions (3.4% vs. 0%) were more common on alirocumab, but there were no significant differences between the arms of this study for serious adverse events. There were slightly more neurocognitive events (2.0 vs. 0%) and abnormal alanine transferase levels (0.7% vs. 0%) in the alirocumab group.

The data are generally consistent with two previously published trials with another PCSK9 inhibitor, according to Dr. Räber. In the randomized GLAGOV trial published more than 5 years ago, evolocumab also produced about a 1% absolute reduction (P < .001) in plaque volume at the end of 78 weeks of follow-up relative to placebo.

However, that trial was limited to patients with coronary artery disease without a recent cardiovascular event. The more recent HUYGENS trial, which was presented virtually at the 2021 annual meeting of the European Society of Cardiology meeting and has not yet been published, looked at one of the endpoints also evaluated in PACMAN-AMI. In that study of 161 randomized NSTEMI patients, there was also about a doubling of fibrous cap thickness (42.7 vs. 21.5 mcm) for the PCSK9 inhibitor relative to placebo.

Clinical endpoints were not compared in either the PACMAN-AMI or HUYGENS trial.
 

PACMAN-AMI confirms plaque stabilization

Nevertheless, the message of plaque stabilization is important, according to Anthony N. DeMaria, MD, Founding Director of the Sulpizio Cardiovascular Center at the University of San Diego. Although he acknowledged that a 1% absolute reduction in mean plaque volume might “make you want to yawn,” he argued that this is a misreading of important changes observed in plaque physiology.

“What we have now is evidence that very low lipid levels result in plaque remodeling. The plaques might not get a whole lot smaller, but the changes are important,” he said, noting, for example, that a thicker fibrous cap and increased plaque stability “clearly plays a role in reducing risk of subsequent events.”

“You cannot help but be impressed by the relationship of lipid lowering and the favorable effect on remodeling,” he added.

The data associating PCSK9 inhibitors with protection from cardiovascular events is already extensive, according to Michael J. Blaha, MD, Director of Clinical Research for Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University, Baltimore, but he called PACMAN-ACS “an extremely relevant study.”

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

The Food and Drug Administration has granted approval to Abbott’s Aveir leadless, single-chamber pacemaker system for patients with bradycardia.

In a press release, Abbott said the device has a unique mapping capability that allows interventionists implanting the device to measure electrical signals within the heart to determine the correct placement before final implantation. Aveir is implanted directly into the right ventricle via a catheter.

The company also said Aveir has a battery life that’s up to twice as long as other commercially available leadless pacemakers when following International Association for Standardization (ISO) standard settings. And the device can be retrieved if necessary, the press release said.

“Leadless pacemakers address known complications associated with traditional pacemakers,” Rahul Doshi, MD, director of electrophysiology at Honor Health in Scottsdale, Ariz., said in the press release. “In addition, the Aveir leadless pacemaker brings unique innovations we’ve been seeking, such as the ability to ensure electrical performance before we commit to placement.”

Investigators of the LEADLESS II phase 2 study reported last year on what they called “key design improvements” of the Aveir device compared to the first leadless pacemaker, the discontinued Nanostim. They included a 12% longer battery life, a shorter and wider form factor, a modified docking button that allows for retrievability, a modified delivery system, and an application-specific integrated circuit chip that can support a dual-chamber pacing system in the future.

The study reported that 96% of the 200 enrolled patients met the primary safety endpoint of no serious device-related adverse events at 6 weeks after implantation. A similar percentage achieved therapeutic pacing and sensing amplitude.

The study also reported that interventionists accurately positioned Aveir the first time or with a single repositioning in 96% of cases.

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

A version of this article first appeared on Medscape.com.

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

A version of this article first appeared on Medscape.com.

U.S. hospitals are being warned to prepare for a potential cyberattack from either the Russian government, criminal gangs resident in Russia, or both, as a result of the invasion of Ukraine and the U.S. and Western countermeasures against the aggressor nation.

The day after President Biden announced that the war had begun, the American Hospital Association (AHA) issued an alert to hospitals. The cybersecurity division of the Department of Health and Human Services (HHS), known as HC3, joined AHA with another public warning to the healthcare system on March 1. The federal government’s Cybersecurity & Infrastructure Security Agency (CISA) issued a “Shield’s Up” alert to private industry, supporting Biden’s March 21 statement about the need to improve domestic cybersecurity.

CISA warned that the Russian invasion of Ukraine could lead to “malicious cyber activity against the U.S. homeland, including as a response to the unprecedented economic costs imposed on Russia by the U.S. and our allies and partners.” The agency noted that the Russian government is currently exploring options for cyberattacks.

John Riggi, the AHA’s national advisor for cybersecurity and risk, and a former senior executive in the FBI’s cyber division, said in an interview, “We are not aware of any cyberattacks related to the current conflict [in Ukraine]. We don’t know of any specific credible threats targeted against U.S. healthcare from the Russian government.”

He added that there have been reports of Russian hackers searching U.S. health IT security systems for weaknesses.
 

Criminal gangs remain a threat

Besides the Russian government, Mr. Riggi said, Russian criminal gangs are another threat to U.S. hospitals and other healthcare providers. Of particular concern, he noted, is the Conti gang, which “has a history of conducting ransomware attacks against U.S. healthcare and the Irish health system.”

On February 25, said Mr. Riggi, the Conti group announced plans “to retaliate against the West for what they viewed as potential cyber aggression by the West against the Russian federation.”

Sophisticated hacker groups like the Conti gang that operate under the protection of the Russian government have “caused the greatest amount of disruption and have cost the most in terms of recovery and lost business,” Mac McMillan, CEO of CynergisTek, a cybersecurity consulting firm, told this news organization.

However, he said, the current threat is greater for two reasons: first, it will likely come directly from the Russian military intelligence service; and second, there are indications that the malware will be more destructive than ransomware. Two new types of malware identified by HC3 — HermeticWiper and WhisperGate — are designed to wipe out the data in their targets’ systems, rather than just encrypting it and disrupting access to data until a ransom is paid.

The Russian military intelligence service, known as the GRU, is extremely capable and dangerous, Mr. McMillan said. He doubts that many healthcare systems, even if they are fairly well prepared, could withstand an attack from this source. And he fully believes that the attack, when it comes, will aim to wipe out data in victims’ systems in order to create as much chaos and disruption as possible in the United States.
 

Hospitals better prepared, but still have gaps

Like Mr. Riggi, Mr. McMillan said that the healthcare industry is better prepared for cyberattacks now than it was in 2017, when the NotPetya assault on Ukraine’s online infrastructure created considerable collateral damage in the United States. However, he said, hospitals still have a long way to go before they can counter and/or recover from a dedicated Russian government cyberattack.

The NotPetya malware, Mr. Riggi said, was of the destructive variety. “That digital virus spread uncontrollably across the globe like a biological virus. All the organizations and institutions that had contact with Ukraine became infected.”

According to an indictment of six GRU officers that the Department of Justice announced in December 2020, NotPetya disrupted operations at a major pharmaceutical company, subsequently revealed to be Merck, and hospitals and other medical facilities in the Heritage Valley Health System in Pennsylvania. In addition, it temporarily shut down the transcription services of Nuance Communications, which lost $98 million as a result. Merck received $1.4 billion from an insurer to cover its NotPetya loss, Bloomberg reported.

That incident prompted the AHA to urge hospitals to use “geo-fencing” to block online communications with Ukraine and neighboring countries. However, Mr. Riggi said, that solution is not too effective because hackers commonly use proxy servers in other countries to forward their malware to the intended target.

The AHA alert included a list of actions that hospitals and health systems could take to reduce their vulnerability to Russian hacking. Besides geo-fencing, the AHA suggested that hospitals:

• Heighten staff awareness of the increased risk of receiving malware-laden phishing emails;
• Identify all international and third-party mission-critical, clinical, and operational services and technology and put in place business continuity plans and downtime procedures;
• Check the redundancy, resiliency, and security of the organization’s network and data backups;
• Document, update, and practice the organization’s incident response plan.

Hospitals increasingly targeted

In recent years, Mr. Riggi noted, hospitals have invested much more in cybersecurity than before, and hospital executives have told him that this is now one of their top priorities, along with COVID-19 and workforce issues. This has been not only because of NotPetya, but also because healthcare facilities are being increasingly attacked by foreign ransomware gangs, he says.

The hospitals’ biggest vulnerabilities, he said, are phishing emails, remote desktop access, and unpatched vulnerabilities, in that order. It’s not easy to remedy the latter, he observed, because hospital networks can include up to 100,000 connected medical devices and other computers that can access the network, both within and outside the hospital.

“With the new work-at-home environment, you may have thousands of employees who are using the network outside the traditional perimeter of the organization,” he pointed out. “There’s no longer that standard firewall that protects everything.” In addition, he said, hospitals also have to depend on vendors to develop patches and implement them.

In Mr. McMillan’s view, the healthcare industry is a decade behind the financial industry and other sectors in cybersecurity. Among other things, he says, “half of our hospitals still don’t have active monitoring on their networks. They don’t have privileged access on their networks. A bunch don’t have segmentation or endpoint protection. There are so many things that hospitals don’t have that they need to fend off these attacks — they’re better off than they were in 2017, but they still aren’t where they need to be.”
 

Physician practices also at risk

Employed physicians, naturally, are in danger of losing access to their electronic health records if their hospital’s network goes down as the result of a cyberattack, he notes. Many community doctors also use the EHR of a local hospital, and they’d be similarly affected, Mr. Riggi noted.

Physician practices might be saved if the attack were directed at the hospital and they could still connect to the EHR through a cloud provider, Mr. McMillan said. But Mr. Riggi stressed that practices still need a plan for their doctors to keep working if they lose access to a hospital EHR.

“The other possibility is that the practice could be targeted,” he added. “As hospitals become more hardened, often these hackers are looking for the weak link. The practices could become victims of increased targeting. And the practice becomes the conduit for malware to go from its system to the hospital and infect the hospital system.”
 

Hackers can hit service suppliers

Hospitals’ mission-critical service suppliers may also be targeted by Russian hackers and others, or they may be the accidental victims of a cyberattack elsewhere, Mr. Riggi noted. In the case of Nuance, he said, the disruption in transcription services affected thousands of U.S. healthcare providers who were unable to access their transcribed notes. This not only harmed patient care, but also meant that hospitals couldn’t fully bill for their services.

Another type of service supplier, he said, was struck with a ransomware attack last year. This was a cloud-based service that operated linear accelerators used in radiation oncology. “So radiation oncology and cancer treatment for patients across the U.S. was disrupted, and radiation oncology was delayed for some patients up to 3 weeks.”

More recently, another cloud-based service called Kronos was struck by ransomware. Because of this incident, payroll and timekeeping services were disrupted across several industries, including healthcare.

A version of this article first appeared on Medscape.com.

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

A version of this article first appeared on Medscape.com.

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

A version of this article first appeared on Medscape.com.

The short interfering RNA (siRNA) agent SLN360 was well tolerated and lowered lipoprotein(a) by up to 98% in volunteers without cardiovascular disease but with elevated Lp(a) in the small dose-ranging APOLLO trial.

Following a single subcutaneous dose of SLN360 (Silence Therapeutics), there was a dose-dependent reduction in Lp(a) plasma levels by a median of 46%, 86%, 96%, and 98% at about 45-60 days with 30-mg, 100-mg, 300-mg, and 600-mg doses, respectively.

Lp(a) levels at 150 days were 70% and 81% below baseline with the 300-and 600-mg doses.

In addition, for participants receiving the two highest doses, apolipoprotein B (apo B) was reduced was 21% and 24%, respectively, and LDL cholesterol (LDL-C), by 21% and 26%, respectively.

“The development of therapies targeting messenger RNA has made possible significant lowering of lipoprotein(a). Whether these reductions can impact on the incidence of ASCVD [atherosclerotic cardiovascular disease] or prevent progression of aortic stenosis remains to be determined but, we think, that optimism is warranted,” said principal investigator Steven E. Nissen, MD, Cleveland Clinic.

The results were presented in a late-breaking clinical trial session at the annual scientific sessions of the American College of Cardiology and published simultaneously in JAMA.

Elevated Lp(a) is a powerful genetic risk factor for ASCVD and aortic stenosis, which affects some 64 million Americans and 1.4 billion people globally. Although several experimental agents are under investigation, no currently approved drugs selectively lower Lp(a).

SLN360 is designed to lower Lp(a) production by using RNA interference to silence messenger RNA transcribed from the LPA gene in liver cells.
 

Testing vacuum

Dr. Nissen said in an interview that one of the big takeaways from the study is the need for greater testing of Lp(a). Automatic assays are available in almost every hospital, but two-unit systems (nmol/L and mg/dL) are used and thresholds for accelerated risk vary. The Cleveland Clinic currently tests all patients in its cardiac critical care unit and its prevention clinic.

“Someone comes in with an MI in their 40s and we measure it and it’s 100, 150 [mg/dL], clearly abnormal, and often these patients don’t have a lot of other risk factors,” Dr. Nissen said. “So the explanation very likely for their premature disease is this risk factor. We now have to educate everybody about the importance of getting it tested and finding out about it.”

During a media briefing, ACC 2022 program cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said testing for Lp(a) is not well reimbursed by insurance providers and that her patients will often cancel the test after learning it won’t be reimbursed because they don’t understand it.

“What Dr. Nissen is telling you: It should be measured in everyone at least once, we all believe that, but it hasn’t made it into the major guidelines,” she added. “I think what we’re going to have to do is have the guidelines mandate it and the insurers will follow.”

Guidelines currently list elevated Lp(a) as a “risk-enhancing factor,” which can help with at least recommending LDL-C treatment in patients with borderline risk and a sky-high Lp(a), noted Dr. Nissen. “But we need to go beyond that.”
 

Safety analyses

The first-in-human APOLLO trial evaluated 32 adults without known ASCVD and an Lp(a) concentration greater than 150 nmol/L (approximately 60 mg/dL) who received one of the four doses of SLN360 or placebo subcutaneously. Participants were monitored in a research unit for the first 24 hours and then followed periodically for up to 150 days. At baseline, their median Lp(a) level was 224 nmol/L, mean apo B level was 85 mg/dL, and mean LDL-C level was 108 mg/dL.

Treatment-emergent adverse events were generally mild, mostly grade 1 injection site reactions (83% at 30 mg, 100% at 100 mg, 67% at 300 mg, and 33% at 600 mg) and headache (33%, 17%, 0%, and 83%).

At the highest dose, C-reactive protein was increased in four patients and neutrophil counts in three. ALT and AST levels were elevated three times above the upper limit of normal in one patient at the lowest dose.

One participant in the lowest-dose group experienced two serious adverse events unrelated to SLN360 at day 45 after receiving a SARS-Co-V-2 vaccine.

Dr. Nissen noted that safety cannot be comprehensively assessed in a trial of this duration or size and that follow-up has been extended to 1 year in the two highest-dose groups.

Enrollment continues in the multiple-ascending dose portion of the study in patients with high Lp(a) and a history of stable ASCVD. A phase 2 study of SLN360 is also planned for the second half of 2022, pending regulatory discussions.
 

But will it reduce ASCVD events?

Study discussant Vera Bittner, MD, MSPH, University of Alabama at Birmingham, said that the development of Lp(a)-specific lowering agents has been a “holy grail” for years and congratulated the authors on a successful trial demonstrating very robust Lp(a) lowering.

She asked Dr. Nissen about the observation in proprotein convertase subtilisin/kexin type 9 inhibitor trials that absolute Lp(a) lowering is greater at higher baseline levels.

Dr. Nissen said this kind of analysis wasn’t possible because of the small sample size but “because these agents so effectively degrade messenger RNA, it’s very likely we will see robust suppression of plasma levels virtually regardless of the baseline level.”

Dr. Bittner also questioned if “LDL-C declined because of the cholesterol content in the lipoprotein(a) or is there some additional effect on LDL particles themselves?”

“It’s a really terrific question that will ultimately need to be answered,” Dr. Nissen replied. “There’s some controversy about the extent to which suppressing lipoprotein(a) will reduce LDL because the assays for LDL are measuring the LDL that’s in lipoprotein(a) and the LDL that is not. ... I think it’s probably a bystander effect, but it may also contribute to efficacy from a morbidity and mortality point of view, which is why we measured it.”

Dr. Bittner also called out the elevation in C-reactive protein and leukocytosis, which has not been seen in other siRNA studies. Dr. Nissen said the increases in C-reactive protein occurred in the first few days after administration and were gone after a week or so. “I don’t see it as a long-term limitation.”

In an accompanying editorial, Brian Ference, MD, MPhil, MSc, University of Cambridge (England), suggests that because circulating Lp(a) particles can progressively become trapped within the artery wall over time, it’s unlikely that lowering Lp(a) for only a few years starting later in life will eliminate the effect of lifelong exposure to Lp(a) and may only cut cardiovascular event risk by about 10%-15%.

He called for continued safety and efficacy evaluation of SLN360 and olpasiran, a similar siRNA agent in early development, and said further insights into whether large absolute reductions in Lp(a) can reduce the risk for major cardiovascular events will come from cardiovascular trials, such as the ongoing phase 3 Lp(a)HORIZON trial. It follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and has Dr. Nissen pulling double duty as study chair.

The study was funded by Silence Therapeutics. Dr. Nissen reported consulting for many pharmaceutical companies, which are directed to pay any renumeration directly to charity. Dr. Bittner reported consultant fees or honoraria from Pfizer; other from AstraZeneca, DalCor, Esperion, and Sanofi-Aventis; and research/research grants from Amgen and Novartis. Dr. Ference reported financial ties to Merck, Novartis, Amgen, Pfizer, Esperion Therapeutics, and numerous other companies.

A version of this article first appeared on Medscape.com.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The new heart failure (HF) guidelines released by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

Catherine Hackett/MDedge News

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

• “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes.
• “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms.
• “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms.
• “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT).

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients,” compared with the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, said in an interview.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Dr. Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities – specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Dr. Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Dr. Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the annual scientific sessions of the American College of Cardiology. The document, developed by the ACC, the American Heart Association, and the Heart Failure Society of America, was published April 1, 2022, in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and the Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA–focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” Douglas L. Mann, MD, Washington University in St. Louis, said in an interview. Dr. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages – the preclinical “at-risk” stage tightening focus on primary prevention – and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved or mildly reduced, or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Dr. Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, Dr. Bozkurt observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests that, “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure,” Dr. Bozkurt said.

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure, obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium-glucose transporter 2 (SGLT2) inhibitors, which have been “game changers,” Dr. Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and [cardiovascular] events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Dr. Bozkurt observed.

Of note, she said, the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Dr. Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Dr. Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Dr. Bozkurt disclosed receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol-Myers Squibb, Sanofi-Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Dr. Mann disclosed receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

A version of this article first appeared on Medscape.com.

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

A version of this article first appeared on Medscape.com.

People who received personalized nutrition education in a series of sessions at their regular grocery store significantly improved adherence to a healthy diet, in a new “first-of-its-kind” study in which scientific researchers partnered with a large supermarket company.

In the SuperWIN study, participants were given individualized advice from supermarket-based dietitians using data on their own buying habits recorded on their supermarket loyalty cards. This was associated with an increased adherence to the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits and whole grains while limiting foods that are high in saturated fat, sugar, and sodium and has been shown to lower blood pressure and LDL cholesterol.

Catherine Hackett/MDedge News

One group of patients also received additional education about healthy eating and meal planning through online technologies, and this group showed even better adherence to the DASH diet.

The study was presented at the annual scientific sessions of the American College of Cardiology by Dylan Steen, MD, adjunct associate professor of medicine at the University of Cincinnati.

“The SuperWIN study provides evidence for the benefit of delivering healthy-eating interventions at modern supermarkets and retail-based clinics,” Dr. Steen said. “It demonstrates the efficacy of dietary interventions harnessing the physical environment of the supermarket, the retail-based dietitians working within the store, and the purchasing data captured on the store’s loyalty cards.”

The study was conducted in partnership with Kroger, the largest supermarket chain in the United States, which also operates a large chain of pharmacies and health clinics.

Dr. Steen said the study was addressing one of the biggest public health problems – unhealthy eating – with an innovative approach. “We need to think about how we can extend the reach of modern health care systems into communities and better deliver services right where people are; meet them where they live,” he said at an ACC press conference.

Commenting on the study at the press conference, Eileen Handberg, PhD, professor of medicine at University of Florida, Gainesville, and immediate past chair of the ACC Cardiovascular Care Team Council, said: “I am amazingly excited about this. There is so much potential here. We have never really taken advantage of the current explosion in retail-based health care before.”

Dr. Handberg suggested the study had major implications for the primary prevention of cardiovascular disease. “Little kids go shopping with their parents, so you have the ability here to change behavior from children on up if you can change the dynamic of the choices they make in the grocery store.”

In his presentation, Dr. Steen noted that, despite many longstanding guidelines on healthy eating, about 75% of Americans still have a poor-quality diet. This trial was conducted to see if a new approach could improve that situation. “If we change the environment in which we deliver dietary education, we can make a difference.”

The SuperWIN trial was conducted in 13 Kroger stores in Ohio and Kentucky. The study enrolled 267 people with at least one cardiovascular risk factor from a primary care network who regularly shopped at one of the study stores. All participants also had to be willing to follow the DASH diet, which was taught at each educational session in the trial.

All participants received one “enhanced” medical nutrition therapy that was guided by the individual’s own dietary intake analytics.

They were then randomly assigned to one of three arms. The control group received no further education. The strategy 1 group received six additional teaching sessions in the supermarket aisles over a 3-month period. Each session was guided by updated individualized purchasing data provided to the dietitian and the participant. 

The strategy 2 group received the same six additional teaching sessions as strategy 1, but they also had some additional teaching on healthy eating and meal planning from a variety of online shopping tools, and nutrition and health care apps.  

“The supermarket analytics were automatically collected so the dietitians could tell what each person liked to eat, how much of each product they were buying and how much they were spending,” Dr. Steen explained.

COVID hit halfway through the trial, and 20 participants were withdrawn for their own safety as they could no longer visit the stores, but the trial continued with the rest of the participants with enhanced safety precautions. The overall analysis cohort was 247 participants.

The average age of the participants was mid-50s, around 70% were female, and most did not have a history of cardiovascular disease.

Eating habits were assessed by three 24-hour dietary recalls assessed at the start of the study and at 3 and 6 months. The DASH score, which is a measure of adherence to the DASH diet, was calculated from this information. The score can range from 0 to 90, with an increased score showing increased adherence.

In one analysis, the researchers compared the DASH scores from the two intervention groups together with the control group, and in a second analysis they compared the scores in the strategy 2 group with those in the strategy 1 group.

Before the pandemic there was “near 100%” attendance for the six visits over the 3-month study period, which Dr. Steen said he thought was “remarkable.” During the pandemic, attendance came down to around 80%.

Results showed that the DASH score increased in all three groups at 3 months, with stepwise increases corresponding to the intensity of the intervention. DASH scores increased by 5.8 points in the control group, by 8.6 points in the strategy 1 group, and by 12.4 points in the strategy 2 group.

DASH scores significantly differed between the two intervention groups and the control group (P = .02). “This shows that purchasing data–guided in-store tours do increase the efficacy of dietary education,” Dr. Steen said.

The difference in scores between the strategy 1 and strategy 2 groups was also significant (P = .01). “This shows online enhancements increase adherence to the DASH diet even further,” Dr. Steen commented

By 6 months, the scores had dropped off a little but were still increased from baseline: by 4.4 points in the control group, 6.6 points in the strategy 1 group, and 8.4 points in the strategy 2 group. “There was again a stepwise increase as the intervention intensified, but there was no longer a significant difference between the interventions and control,” Dr. Steen noted.

Secondary endpoints included blood pressure and body mass index. Systolic blood pressure decreased slightly in all three groups: by 2.8 mm Hg in the control group, 6.6 mm Hg in the strategy 1 group, and 5.7 mm Hg in the strategy 2 group. Body mass index was reduced by 0.2, 0.4 and 0.8, respectively, but the between-group differences were not significant.

Dr. Steen said this is the first study of its kind to date in which scientific researchers collaborated with a large supermarket chain. He explained they also involved a primary care network so that health care utilization information will be available.

“We can the integrate retail-based health care information with traditional health care information. And we can start to look at downstream health care utilization and cost outcomes as well, which will be important as we start to think how to evolve the health care system,” he commented. “The hope is that we can get more scientists working with more retailers to really drive the evidence to shape the evolution of our health care system.”

Challenges ahead

Dr. Handberg pointed out there would be challenges in reaching the underserved population who do not shop at the major supermarkets. “We need to figure out how to get partnerships across the whole spectrum of grocery stores.”

She also noted that 3 months (the duration of the study intervention) was not much time to change the eating habits of a family. “Interventions may have to be a bit more intensive to get the change in blood pressure and weight that we would want to see.”

Dr Handberg hoped the major grocery store companies will see the opportunities in this approach. “Changing behavior is very complicated, and the key will be how to make people stick with the changes. But grocery stores are smart. They have got us going to their pharmacies, so getting us to see a dietitian is not that much of a stretch.”

Moderator of the ACC late-breaker session at which the study was presented, Pamela Morris, MD, from the Medical University of South Carolina, Charleston, who is also ACC annual scientific session chair, asked whether the approach could be sustained.

“I am thinking back to the barber shop study of blood pressure treatment and to my knowledge those PharmDs are no longer in those barbershops, taking blood pressures, counseling patients, and prescribing antihypertensives. So is Kroger maintaining a long-term commitment to providing this education, or how can this be financed over the long term?” she asked.

Dr. Steen replied that he believed sustainability to be one of the key strengths of this model. “Retail-based health care is exploding in the U.S. The number of retail outlets offering a comprehensive list of services is going up all the time. These programs exist regardless of whether this trial was conducted or not.”

But Dr. Steen stressed that having an evidence base will be critically important.

“Validation is an enormous part of this evolution in retail-based health care – not only to figure out what works but also to engage payors and others in the process of supporting these interventions. I think the sustainability is there – it is sort of baked into the model – but research will be a huge part of cementing this in and helping us to understand what we should do.”

The study was funded by Kroger. Dr. Steen is a consultant for Sanofi and CEO and cofounder of High Enroll.

A version of this article first appeared on Medscape.com.

WASHINGTON – Treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy who remained on treatment with the investigational agent mavacamten for a median of 62 weeks continued to show the same level of safe response to the drug as seen after the first 30 weeks on treatment in the pivotal trial for this agent.

The new findings from longer-term treatment bode well for mavacamten. That’s because if the drug is used in routine practice to avoid the need for surgery or an invasive intervention to reduce blockage of a patient’s left ventricular outflow tract, the duration of mavacamten treatment will likely need to continue for many years and even for decades, said Florian Rader, MD, who presented the results at the annual scientific sessions of the American College of Cardiology.

“In practice, mavacamten will probably be used for many, many years, especially as it replaces septal-reduction therapy, so we need long-term data,” noted Dr. Rader during a press briefing on his report. “I’m very happy with the long-term data” in the follow-up study.

The Food and Drug Administration is currently considering whether to approve mavacamten for routine marketing to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with a decision expected by the end of April 2022.

The study Dr. Rader reported followed 231 patients with symptomatic oHCM who had completed the 30-week pivotal trial of mavacamten, EXPLORER-HCM, and opted to continue on open-label extended treatment with mavacamten, either continuing the treatment they started during the trial or crossing over to receive mavacamten after receiving placebo during the trial.

The major findings from EXPLORER-LTE (long-term extension) were that continued treatment for a median of about 62 weeks maintained the safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase, said Dr. Rader, codirector of the Clinic for Hypertrophic Cardiomyopathy and Aortopathies at Cedars-Sinai Medical Center in Los Angeles.

‘Almost revolutionary’

Mavacamten represents “an almost revolutionary change” for treating oHCM, commented Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis. “Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” said Dr. Guglin during the press briefing.

Mitchel L. Zoler/MDedge News

“All of us who care for patients with oHCM have looked forward to having a disease-specific therapy. It is encouraging to see that the safety and efficacy remained high with long-term follow-up,” commented Kyle W. Klarich, MD, a professor and cardiologist who specializes in treating patients with HCM at the Mayo Clinic in Rochester, Minn.

Mavacamten is a direct myosin inhibitor that reduces the excess number of myosin-actin cross bridges that form in patients with oHCM, and thereby directly targets the pathophysiology that underlies the disorder, explained Dr. Rader.

The patients on mavacamten included in the long-term extension reported by Dr. Rader averaged 60 years of age, and 61% were men. They averaged a 35.6–mm Hg drop in their resting left ventricular outflow tract (LVOT) gradient after 48 weeks on treatment, and a 32.8–mm Hg reduction after 84 weeks. When the investigators measured their LVOT gradient during a valsalva maneuver, their reductions from baseline averaged 45.3 mm Hg after 48 weeks and 46.4 mm Hg after 84 weeks.

Mitchel L. Zoler/MDedge News

Resting left ventricular ejection fraction also fell, by an average of 7.0 percentage points from baseline after 48 weeks, and by an average of 9.0 percentage points after 84 weeks. After 48 weeks on treatment, 68% of patients had at least a one-class improvement from baseline in their New York Heart Association functional class.

The safety results showed that most treatment-related adverse events were mild or moderate, and about 2% of patients had a serious drug-related adverse event. Ten of the 231 patients discontinued mavacamten because of a treated-related adverse event.

EXPLORER-HCM and EXPLORER-LTE were sponsored by MyoKardia, the company that is developing mavacamten and which is now owned by Bristol-Myers Squibb. Dr. Rader has been a consultant to MyoKardia as well as to Medtronic and ReCor. Dr. Guglin and Dr. Klarich had no disclosures.

WASHINGTON – Treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy who remained on treatment with the investigational agent mavacamten for a median of 62 weeks continued to show the same level of safe response to the drug as seen after the first 30 weeks on treatment in the pivotal trial for this agent.

The new findings from longer-term treatment bode well for mavacamten. That’s because if the drug is used in routine practice to avoid the need for surgery or an invasive intervention to reduce blockage of a patient’s left ventricular outflow tract, the duration of mavacamten treatment will likely need to continue for many years and even for decades, said Florian Rader, MD, who presented the results at the annual scientific sessions of the American College of Cardiology.

“In practice, mavacamten will probably be used for many, many years, especially as it replaces septal-reduction therapy, so we need long-term data,” noted Dr. Rader during a press briefing on his report. “I’m very happy with the long-term data” in the follow-up study.

The Food and Drug Administration is currently considering whether to approve mavacamten for routine marketing to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with a decision expected by the end of April 2022.

The study Dr. Rader reported followed 231 patients with symptomatic oHCM who had completed the 30-week pivotal trial of mavacamten, EXPLORER-HCM, and opted to continue on open-label extended treatment with mavacamten, either continuing the treatment they started during the trial or crossing over to receive mavacamten after receiving placebo during the trial.

The major findings from EXPLORER-LTE (long-term extension) were that continued treatment for a median of about 62 weeks maintained the safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase, said Dr. Rader, codirector of the Clinic for Hypertrophic Cardiomyopathy and Aortopathies at Cedars-Sinai Medical Center in Los Angeles.

‘Almost revolutionary’

Mavacamten represents “an almost revolutionary change” for treating oHCM, commented Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis. “Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” said Dr. Guglin during the press briefing.

Mitchel L. Zoler/MDedge News

“All of us who care for patients with oHCM have looked forward to having a disease-specific therapy. It is encouraging to see that the safety and efficacy remained high with long-term follow-up,” commented Kyle W. Klarich, MD, a professor and cardiologist who specializes in treating patients with HCM at the Mayo Clinic in Rochester, Minn.

Mavacamten is a direct myosin inhibitor that reduces the excess number of myosin-actin cross bridges that form in patients with oHCM, and thereby directly targets the pathophysiology that underlies the disorder, explained Dr. Rader.

The patients on mavacamten included in the long-term extension reported by Dr. Rader averaged 60 years of age, and 61% were men. They averaged a 35.6–mm Hg drop in their resting left ventricular outflow tract (LVOT) gradient after 48 weeks on treatment, and a 32.8–mm Hg reduction after 84 weeks. When the investigators measured their LVOT gradient during a valsalva maneuver, their reductions from baseline averaged 45.3 mm Hg after 48 weeks and 46.4 mm Hg after 84 weeks.

Mitchel L. Zoler/MDedge News

Resting left ventricular ejection fraction also fell, by an average of 7.0 percentage points from baseline after 48 weeks, and by an average of 9.0 percentage points after 84 weeks. After 48 weeks on treatment, 68% of patients had at least a one-class improvement from baseline in their New York Heart Association functional class.

The safety results showed that most treatment-related adverse events were mild or moderate, and about 2% of patients had a serious drug-related adverse event. Ten of the 231 patients discontinued mavacamten because of a treated-related adverse event.

EXPLORER-HCM and EXPLORER-LTE were sponsored by MyoKardia, the company that is developing mavacamten and which is now owned by Bristol-Myers Squibb. Dr. Rader has been a consultant to MyoKardia as well as to Medtronic and ReCor. Dr. Guglin and Dr. Klarich had no disclosures.

WASHINGTON – Treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy who remained on treatment with the investigational agent mavacamten for a median of 62 weeks continued to show the same level of safe response to the drug as seen after the first 30 weeks on treatment in the pivotal trial for this agent.

The new findings from longer-term treatment bode well for mavacamten. That’s because if the drug is used in routine practice to avoid the need for surgery or an invasive intervention to reduce blockage of a patient’s left ventricular outflow tract, the duration of mavacamten treatment will likely need to continue for many years and even for decades, said Florian Rader, MD, who presented the results at the annual scientific sessions of the American College of Cardiology.

“In practice, mavacamten will probably be used for many, many years, especially as it replaces septal-reduction therapy, so we need long-term data,” noted Dr. Rader during a press briefing on his report. “I’m very happy with the long-term data” in the follow-up study.

The Food and Drug Administration is currently considering whether to approve mavacamten for routine marketing to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with a decision expected by the end of April 2022.

The study Dr. Rader reported followed 231 patients with symptomatic oHCM who had completed the 30-week pivotal trial of mavacamten, EXPLORER-HCM, and opted to continue on open-label extended treatment with mavacamten, either continuing the treatment they started during the trial or crossing over to receive mavacamten after receiving placebo during the trial.

The major findings from EXPLORER-LTE (long-term extension) were that continued treatment for a median of about 62 weeks maintained the safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase, said Dr. Rader, codirector of the Clinic for Hypertrophic Cardiomyopathy and Aortopathies at Cedars-Sinai Medical Center in Los Angeles.

‘Almost revolutionary’

Mavacamten represents “an almost revolutionary change” for treating oHCM, commented Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis. “Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” said Dr. Guglin during the press briefing.

Mitchel L. Zoler/MDedge News

“All of us who care for patients with oHCM have looked forward to having a disease-specific therapy. It is encouraging to see that the safety and efficacy remained high with long-term follow-up,” commented Kyle W. Klarich, MD, a professor and cardiologist who specializes in treating patients with HCM at the Mayo Clinic in Rochester, Minn.

Mavacamten is a direct myosin inhibitor that reduces the excess number of myosin-actin cross bridges that form in patients with oHCM, and thereby directly targets the pathophysiology that underlies the disorder, explained Dr. Rader.

The patients on mavacamten included in the long-term extension reported by Dr. Rader averaged 60 years of age, and 61% were men. They averaged a 35.6–mm Hg drop in their resting left ventricular outflow tract (LVOT) gradient after 48 weeks on treatment, and a 32.8–mm Hg reduction after 84 weeks. When the investigators measured their LVOT gradient during a valsalva maneuver, their reductions from baseline averaged 45.3 mm Hg after 48 weeks and 46.4 mm Hg after 84 weeks.

Mitchel L. Zoler/MDedge News

Resting left ventricular ejection fraction also fell, by an average of 7.0 percentage points from baseline after 48 weeks, and by an average of 9.0 percentage points after 84 weeks. After 48 weeks on treatment, 68% of patients had at least a one-class improvement from baseline in their New York Heart Association functional class.

The safety results showed that most treatment-related adverse events were mild or moderate, and about 2% of patients had a serious drug-related adverse event. Ten of the 231 patients discontinued mavacamten because of a treated-related adverse event.

EXPLORER-HCM and EXPLORER-LTE were sponsored by MyoKardia, the company that is developing mavacamten and which is now owned by Bristol-Myers Squibb. Dr. Rader has been a consultant to MyoKardia as well as to Medtronic and ReCor. Dr. Guglin and Dr. Klarich had no disclosures.

An investigational drug targeting a novel cholesterol pathway has shown disappointing results in the TRANSLATE-TIMI 70 phase 2b study.

Vupanorsen is an antisense oligonucleotide targeting hepatic angiopoietin-like protein 3 (ANGPTL3), a protein that inhibits enzymes involved in the metabolism of triglyceride and cholesterol. Inhibition of ANGPTL3 is one of several novel targets for lowering triglycerides and non-HDL cholesterol.

Results of the TRANSLATE-TIMI 70 study were presented at the annual scientific sessions of the American College of Cardiology by Brian Bergmark, MD, a cardiologist at Brigham and Women’s Hospital, Boston. They were also simultaneously published online in Circulation.

“While vupanorsen significantly reduced triglycerides and non-HDL cholesterol, the reduction in non-HDL cholesterol of 22%-27% was not to a degree that was clinically meaningful for cardiovascular risk reduction, and there were also some potentially important safety issues,” Dr. Bergmark said in an interview.

Pfizer has announced that, after reviewing the results of this study, it is discontinuing development of vupanorsen and will return rights to Ionis, from which it licensed the investigational therapy in 2019.

In response to a question at an ACC press conference on whether there could be any future for the drug, Dr. Bergmark said that “the degree of lipid lowering was not as much as what had been suggested was potentially possible by acting on this pathway, and then there are the additional safety concerns. So, for the specific question of what we were looking at – cardiovascular risk reduction by impacting non-HDL cholesterol and apo [apolipoprotein] B – the modest efficacy paired with the safety concerns does not look favorable for future development of this drug.”

But he added: “Whether some other person or company wants to think about triglyceride lowering and try to find a dose that is a bit safer, that is not for me to say.”

In his ACC presentation, Dr. Bergmark explained that ANGPTL3 is a protein secreted by the liver that inhibits lipases, including lipoprotein lipase. Loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids and a monoclonal antibody targeting ANGPTL3, evinacumab (Evkeeza, Regeneron), is approved as an intravenous infusion for the treatment of familial hypercholesterolemia. Vupanorsen is a second-generation antisense oligonucleotide targeting hepatic ANGPTL3 messenger RNA with a potential role for cardiovascular risk reduction.

A previous phase 2a study of vupanorsen in patients with hypertriglyceridemia, hepatic steatosis, and type 2 diabetes mellitus showed significant reductions in triglycerides at all doses studied, as well as reductions in non-HDL cholesterol at the highest doses (80 mg per month given by subcutaneous injection).

Dr. Bergmark noted that, because a potential cardiovascular benefit of vupanorsen would best be reflected by its effects on non-HDL cholesterol, the current TRANSLATE-TIMI 70 trial was designed to assess the effect of escalating doses of vupanorsen on non-HDL cholesterol levels in statin-treated adults with hyperlipidemia.

For the study, 286 adults with non-HDL cholesterol levels of 100 mg/dL or greater (median, 132 mg/dL) and triglyceride levels of 150-500 mg/dL (median, 216 mg/dL) who were receiving statin therapy were randomly assigned to placebo or one of seven vupanorsen dose regimens (80, 120, or 160 mg every 4 weeks or 60, 80, 120, or 160 mg every 2 weeks). All doses were given by subcutaneous injection.

The study population was said to reflect “a typical cohort intended for cardiovascular risk reduction, with type 2 diabetes in approximately one-half of patients and prevalent atherosclerotic cardiovascular disease in a substantial portion,” the researchers wrote in the published report.

The primary endpoint was placebo-adjusted percentage change from baseline in non-HDL cholesterol at 24 weeks. Secondary endpoints included placebo-adjusted percentage changes from baseline in triglycerides, LDL cholesterol, apo B, and ANGPTL3.

Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL cholesterol ranging from 22.0% in the group receiving 60 mg every 2 weeks to 27.7% in the group receiving 80 mg every 2 weeks, but there did not appear to be a dose response.

Regarding additional lipid endpoints, vupanorsen reduced triglyceride levels in a dose-dependent manner, ranging from 41.3% in the group receiving 120 mg every 4 weeks to 56.8% in the group receiving 160 mg every 2 weeks.

The effects of vupanorsen on LDL cholesterol and apo B were more modest and without a clear dose response. Vupanorsen also lowered HDL cholesterol levels at all doses studied, and there was no significant change in high-sensitivity C-reactive protein at any dose.

Liver enzymes and hepatic fat increases of concern

In terms of safety, vupanorsen treatment was linked to liver enzyme elevations; more than three-times elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively). Injection site reactions were also an issue, including recall reactions at sites of previous injections when subsequent injections were given. In addition, there was a dose-related increase (up to 76%) in hepatic fat fraction.

In the Circulation paper, the researchers say it is unclear whether the increases in hepatic fat fraction and liver enzymes reflect a metabolic effect of vupanorsen specifically or an off-target effect resulting from hepatic targeting of ANGPTL3. “Regardless, these are medically meaningful findings with important safety ramifications,” they wrote.

They pointed out that, whereas the reduction in ANGPTL3 levels increased with total monthly dose of vupanorsen, there was no clear dose-response reduction in LDL cholesterol, apo B, or non-HDL cholesterol.

In comparison, evinacumab, a monoclonal antibody against ANGPTL3 that is thought to cause near-total suppression of ANGPTL3 activity, reduces apo B levels by more than 40% in adults with refractory hypercholesterolemia or homozygous familial hypercholesterolemia.

Asked why vupanorsen showed less of an effect on non-HDL cholesterol than evinacumab, Dr. Bergmark suggested that the monoclonal antibody may achieve greater inhibition of ANGPTL3. “It may be that near complete suppression is needed to obtain clinically meaningful reductions in apo B and non-HDL cholesterol. That is a speculative and simplistic explanation,” he commented.

Conversely, reductions in triglycerides with vupanorsen showed a dose-response relationship, mirroring the reduction in ANGPTL3 and consistent with the expected increases in lipoprotein lipase activity, the researchers reported.

They note that the “relatively muted effect on apo B levels” suggests that vupanorsen is primarily decreasing the triglyceride and, to a lesser extent, cholesterol content of very low-density lipoprotein cholesterol particles rather than reducing the number of such particles.

“These observations have important implications for the potential ability of this mechanism to reduce lipid-mediated cardiovascular risk, which largely appears to be a function of the number of ApoB-containing lipoproteins,” they said.

Designated discussant of the study at the ACC late-breaking session, Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston, asked Dr. Bergmark what minimum degree of non-HDL cholesterol reduction would be compelling for a new drug to be considered for wide-scale use.

Dr. Bergmark replied there was no clear to answer to that question, as it would depend on many factors, including the risk of the population and the time horizon involved. But he added: “I think a minimum of at least a 30%-40% reduction in non-HDL cholesterol would be needed for a meaningful reduction in cardiovascular risk across a variety of settings.”

The TRANSLATE-TIMI 70 study was funded by Pfizer. Dr. Bergmark is a member of the TIMI Study Group, which has received institutional grant support through Brigham and Women’s Hospital from numerous pharmaceutical companies. Dr. Bergmark also reported receiving grant support through Brigham and Women’s Hospital from Pfizer, Ionis, AstraZeneca, and Abbott Vascular and consulting/personal fees from Abiomed, CSI, Philips, Abbott Vascular, Servier, DaiichiSankyo, Janssen, and Quark.

A version of this article first appeared on Medscape.com.

An investigational drug targeting a novel cholesterol pathway has shown disappointing results in the TRANSLATE-TIMI 70 phase 2b study.

Vupanorsen is an antisense oligonucleotide targeting hepatic angiopoietin-like protein 3 (ANGPTL3), a protein that inhibits enzymes involved in the metabolism of triglyceride and cholesterol. Inhibition of ANGPTL3 is one of several novel targets for lowering triglycerides and non-HDL cholesterol.

Results of the TRANSLATE-TIMI 70 study were presented at the annual scientific sessions of the American College of Cardiology by Brian Bergmark, MD, a cardiologist at Brigham and Women’s Hospital, Boston. They were also simultaneously published online in Circulation.

“While vupanorsen significantly reduced triglycerides and non-HDL cholesterol, the reduction in non-HDL cholesterol of 22%-27% was not to a degree that was clinically meaningful for cardiovascular risk reduction, and there were also some potentially important safety issues,” Dr. Bergmark said in an interview.

Pfizer has announced that, after reviewing the results of this study, it is discontinuing development of vupanorsen and will return rights to Ionis, from which it licensed the investigational therapy in 2019.

In response to a question at an ACC press conference on whether there could be any future for the drug, Dr. Bergmark said that “the degree of lipid lowering was not as much as what had been suggested was potentially possible by acting on this pathway, and then there are the additional safety concerns. So, for the specific question of what we were looking at – cardiovascular risk reduction by impacting non-HDL cholesterol and apo [apolipoprotein] B – the modest efficacy paired with the safety concerns does not look favorable for future development of this drug.”

But he added: “Whether some other person or company wants to think about triglyceride lowering and try to find a dose that is a bit safer, that is not for me to say.”

In his ACC presentation, Dr. Bergmark explained that ANGPTL3 is a protein secreted by the liver that inhibits lipases, including lipoprotein lipase. Loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids and a monoclonal antibody targeting ANGPTL3, evinacumab (Evkeeza, Regeneron), is approved as an intravenous infusion for the treatment of familial hypercholesterolemia. Vupanorsen is a second-generation antisense oligonucleotide targeting hepatic ANGPTL3 messenger RNA with a potential role for cardiovascular risk reduction.

A previous phase 2a study of vupanorsen in patients with hypertriglyceridemia, hepatic steatosis, and type 2 diabetes mellitus showed significant reductions in triglycerides at all doses studied, as well as reductions in non-HDL cholesterol at the highest doses (80 mg per month given by subcutaneous injection).

Dr. Bergmark noted that, because a potential cardiovascular benefit of vupanorsen would best be reflected by its effects on non-HDL cholesterol, the current TRANSLATE-TIMI 70 trial was designed to assess the effect of escalating doses of vupanorsen on non-HDL cholesterol levels in statin-treated adults with hyperlipidemia.

For the study, 286 adults with non-HDL cholesterol levels of 100 mg/dL or greater (median, 132 mg/dL) and triglyceride levels of 150-500 mg/dL (median, 216 mg/dL) who were receiving statin therapy were randomly assigned to placebo or one of seven vupanorsen dose regimens (80, 120, or 160 mg every 4 weeks or 60, 80, 120, or 160 mg every 2 weeks). All doses were given by subcutaneous injection.

The study population was said to reflect “a typical cohort intended for cardiovascular risk reduction, with type 2 diabetes in approximately one-half of patients and prevalent atherosclerotic cardiovascular disease in a substantial portion,” the researchers wrote in the published report.

The primary endpoint was placebo-adjusted percentage change from baseline in non-HDL cholesterol at 24 weeks. Secondary endpoints included placebo-adjusted percentage changes from baseline in triglycerides, LDL cholesterol, apo B, and ANGPTL3.

Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL cholesterol ranging from 22.0% in the group receiving 60 mg every 2 weeks to 27.7% in the group receiving 80 mg every 2 weeks, but there did not appear to be a dose response.

Regarding additional lipid endpoints, vupanorsen reduced triglyceride levels in a dose-dependent manner, ranging from 41.3% in the group receiving 120 mg every 4 weeks to 56.8% in the group receiving 160 mg every 2 weeks.

The effects of vupanorsen on LDL cholesterol and apo B were more modest and without a clear dose response. Vupanorsen also lowered HDL cholesterol levels at all doses studied, and there was no significant change in high-sensitivity C-reactive protein at any dose.

Liver enzymes and hepatic fat increases of concern

In terms of safety, vupanorsen treatment was linked to liver enzyme elevations; more than three-times elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively). Injection site reactions were also an issue, including recall reactions at sites of previous injections when subsequent injections were given. In addition, there was a dose-related increase (up to 76%) in hepatic fat fraction.

In the Circulation paper, the researchers say it is unclear whether the increases in hepatic fat fraction and liver enzymes reflect a metabolic effect of vupanorsen specifically or an off-target effect resulting from hepatic targeting of ANGPTL3. “Regardless, these are medically meaningful findings with important safety ramifications,” they wrote.

They pointed out that, whereas the reduction in ANGPTL3 levels increased with total monthly dose of vupanorsen, there was no clear dose-response reduction in LDL cholesterol, apo B, or non-HDL cholesterol.

In comparison, evinacumab, a monoclonal antibody against ANGPTL3 that is thought to cause near-total suppression of ANGPTL3 activity, reduces apo B levels by more than 40% in adults with refractory hypercholesterolemia or homozygous familial hypercholesterolemia.

Asked why vupanorsen showed less of an effect on non-HDL cholesterol than evinacumab, Dr. Bergmark suggested that the monoclonal antibody may achieve greater inhibition of ANGPTL3. “It may be that near complete suppression is needed to obtain clinically meaningful reductions in apo B and non-HDL cholesterol. That is a speculative and simplistic explanation,” he commented.

Conversely, reductions in triglycerides with vupanorsen showed a dose-response relationship, mirroring the reduction in ANGPTL3 and consistent with the expected increases in lipoprotein lipase activity, the researchers reported.

They note that the “relatively muted effect on apo B levels” suggests that vupanorsen is primarily decreasing the triglyceride and, to a lesser extent, cholesterol content of very low-density lipoprotein cholesterol particles rather than reducing the number of such particles.

“These observations have important implications for the potential ability of this mechanism to reduce lipid-mediated cardiovascular risk, which largely appears to be a function of the number of ApoB-containing lipoproteins,” they said.

Designated discussant of the study at the ACC late-breaking session, Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston, asked Dr. Bergmark what minimum degree of non-HDL cholesterol reduction would be compelling for a new drug to be considered for wide-scale use.

Dr. Bergmark replied there was no clear to answer to that question, as it would depend on many factors, including the risk of the population and the time horizon involved. But he added: “I think a minimum of at least a 30%-40% reduction in non-HDL cholesterol would be needed for a meaningful reduction in cardiovascular risk across a variety of settings.”

The TRANSLATE-TIMI 70 study was funded by Pfizer. Dr. Bergmark is a member of the TIMI Study Group, which has received institutional grant support through Brigham and Women’s Hospital from numerous pharmaceutical companies. Dr. Bergmark also reported receiving grant support through Brigham and Women’s Hospital from Pfizer, Ionis, AstraZeneca, and Abbott Vascular and consulting/personal fees from Abiomed, CSI, Philips, Abbott Vascular, Servier, DaiichiSankyo, Janssen, and Quark.

A version of this article first appeared on Medscape.com.

An investigational drug targeting a novel cholesterol pathway has shown disappointing results in the TRANSLATE-TIMI 70 phase 2b study.

Vupanorsen is an antisense oligonucleotide targeting hepatic angiopoietin-like protein 3 (ANGPTL3), a protein that inhibits enzymes involved in the metabolism of triglyceride and cholesterol. Inhibition of ANGPTL3 is one of several novel targets for lowering triglycerides and non-HDL cholesterol.

Results of the TRANSLATE-TIMI 70 study were presented at the annual scientific sessions of the American College of Cardiology by Brian Bergmark, MD, a cardiologist at Brigham and Women’s Hospital, Boston. They were also simultaneously published online in Circulation.

“While vupanorsen significantly reduced triglycerides and non-HDL cholesterol, the reduction in non-HDL cholesterol of 22%-27% was not to a degree that was clinically meaningful for cardiovascular risk reduction, and there were also some potentially important safety issues,” Dr. Bergmark said in an interview.

Pfizer has announced that, after reviewing the results of this study, it is discontinuing development of vupanorsen and will return rights to Ionis, from which it licensed the investigational therapy in 2019.

In response to a question at an ACC press conference on whether there could be any future for the drug, Dr. Bergmark said that “the degree of lipid lowering was not as much as what had been suggested was potentially possible by acting on this pathway, and then there are the additional safety concerns. So, for the specific question of what we were looking at – cardiovascular risk reduction by impacting non-HDL cholesterol and apo [apolipoprotein] B – the modest efficacy paired with the safety concerns does not look favorable for future development of this drug.”

But he added: “Whether some other person or company wants to think about triglyceride lowering and try to find a dose that is a bit safer, that is not for me to say.”

In his ACC presentation, Dr. Bergmark explained that ANGPTL3 is a protein secreted by the liver that inhibits lipases, including lipoprotein lipase. Loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids and a monoclonal antibody targeting ANGPTL3, evinacumab (Evkeeza, Regeneron), is approved as an intravenous infusion for the treatment of familial hypercholesterolemia. Vupanorsen is a second-generation antisense oligonucleotide targeting hepatic ANGPTL3 messenger RNA with a potential role for cardiovascular risk reduction.

A previous phase 2a study of vupanorsen in patients with hypertriglyceridemia, hepatic steatosis, and type 2 diabetes mellitus showed significant reductions in triglycerides at all doses studied, as well as reductions in non-HDL cholesterol at the highest doses (80 mg per month given by subcutaneous injection).

Dr. Bergmark noted that, because a potential cardiovascular benefit of vupanorsen would best be reflected by its effects on non-HDL cholesterol, the current TRANSLATE-TIMI 70 trial was designed to assess the effect of escalating doses of vupanorsen on non-HDL cholesterol levels in statin-treated adults with hyperlipidemia.

For the study, 286 adults with non-HDL cholesterol levels of 100 mg/dL or greater (median, 132 mg/dL) and triglyceride levels of 150-500 mg/dL (median, 216 mg/dL) who were receiving statin therapy were randomly assigned to placebo or one of seven vupanorsen dose regimens (80, 120, or 160 mg every 4 weeks or 60, 80, 120, or 160 mg every 2 weeks). All doses were given by subcutaneous injection.

The study population was said to reflect “a typical cohort intended for cardiovascular risk reduction, with type 2 diabetes in approximately one-half of patients and prevalent atherosclerotic cardiovascular disease in a substantial portion,” the researchers wrote in the published report.

The primary endpoint was placebo-adjusted percentage change from baseline in non-HDL cholesterol at 24 weeks. Secondary endpoints included placebo-adjusted percentage changes from baseline in triglycerides, LDL cholesterol, apo B, and ANGPTL3.

Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL cholesterol ranging from 22.0% in the group receiving 60 mg every 2 weeks to 27.7% in the group receiving 80 mg every 2 weeks, but there did not appear to be a dose response.

Regarding additional lipid endpoints, vupanorsen reduced triglyceride levels in a dose-dependent manner, ranging from 41.3% in the group receiving 120 mg every 4 weeks to 56.8% in the group receiving 160 mg every 2 weeks.

The effects of vupanorsen on LDL cholesterol and apo B were more modest and without a clear dose response. Vupanorsen also lowered HDL cholesterol levels at all doses studied, and there was no significant change in high-sensitivity C-reactive protein at any dose.

Liver enzymes and hepatic fat increases of concern

In terms of safety, vupanorsen treatment was linked to liver enzyme elevations; more than three-times elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively). Injection site reactions were also an issue, including recall reactions at sites of previous injections when subsequent injections were given. In addition, there was a dose-related increase (up to 76%) in hepatic fat fraction.

In the Circulation paper, the researchers say it is unclear whether the increases in hepatic fat fraction and liver enzymes reflect a metabolic effect of vupanorsen specifically or an off-target effect resulting from hepatic targeting of ANGPTL3. “Regardless, these are medically meaningful findings with important safety ramifications,” they wrote.

They pointed out that, whereas the reduction in ANGPTL3 levels increased with total monthly dose of vupanorsen, there was no clear dose-response reduction in LDL cholesterol, apo B, or non-HDL cholesterol.

In comparison, evinacumab, a monoclonal antibody against ANGPTL3 that is thought to cause near-total suppression of ANGPTL3 activity, reduces apo B levels by more than 40% in adults with refractory hypercholesterolemia or homozygous familial hypercholesterolemia.

Asked why vupanorsen showed less of an effect on non-HDL cholesterol than evinacumab, Dr. Bergmark suggested that the monoclonal antibody may achieve greater inhibition of ANGPTL3. “It may be that near complete suppression is needed to obtain clinically meaningful reductions in apo B and non-HDL cholesterol. That is a speculative and simplistic explanation,” he commented.

Conversely, reductions in triglycerides with vupanorsen showed a dose-response relationship, mirroring the reduction in ANGPTL3 and consistent with the expected increases in lipoprotein lipase activity, the researchers reported.

They note that the “relatively muted effect on apo B levels” suggests that vupanorsen is primarily decreasing the triglyceride and, to a lesser extent, cholesterol content of very low-density lipoprotein cholesterol particles rather than reducing the number of such particles.

“These observations have important implications for the potential ability of this mechanism to reduce lipid-mediated cardiovascular risk, which largely appears to be a function of the number of ApoB-containing lipoproteins,” they said.

Designated discussant of the study at the ACC late-breaking session, Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston, asked Dr. Bergmark what minimum degree of non-HDL cholesterol reduction would be compelling for a new drug to be considered for wide-scale use.

Dr. Bergmark replied there was no clear to answer to that question, as it would depend on many factors, including the risk of the population and the time horizon involved. But he added: “I think a minimum of at least a 30%-40% reduction in non-HDL cholesterol would be needed for a meaningful reduction in cardiovascular risk across a variety of settings.”

The TRANSLATE-TIMI 70 study was funded by Pfizer. Dr. Bergmark is a member of the TIMI Study Group, which has received institutional grant support through Brigham and Women’s Hospital from numerous pharmaceutical companies. Dr. Bergmark also reported receiving grant support through Brigham and Women’s Hospital from Pfizer, Ionis, AstraZeneca, and Abbott Vascular and consulting/personal fees from Abiomed, CSI, Philips, Abbott Vascular, Servier, DaiichiSankyo, Janssen, and Quark.

A version of this article first appeared on Medscape.com.