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Valvular disease and COVID-19 are a deadly mix; don’t delay intervention
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
FROM TCT 2020
VOYAGER PAD: Paclitaxel-coated devices don’t increase mortality
a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.
Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.
“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”
VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.
Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.
In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.
“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.
There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.
Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.
Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”
“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.
“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”
Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”
The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.
a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.
Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.
“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”
VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.
Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.
In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.
“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.
There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.
Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.
Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”
“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.
“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”
Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”
The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.
a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.
Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.
“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”
VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.
Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.
In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.
“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.
There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.
Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.
Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”
“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.
“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”
Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”
The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.
FROM TCT 2020
MitraClip effective for post-MI acute mitral regurgitation with cardiogenic shock
Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.
“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.
Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.
He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
Procedural success
Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.
“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.
Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.
At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.
At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
Longer-term clinical outcomes
At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.
In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.
Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.
“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.
“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”
“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”
At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.
“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.
While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.
Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.
Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.
“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.
Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.
He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
Procedural success
Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.
“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.
Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.
At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.
At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
Longer-term clinical outcomes
At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.
In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.
Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.
“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.
“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”
“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”
At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.
“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.
While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.
Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.
Percutaneous mitral valve repair with the MitraClip appears to be a safe, effective, and life-saving new treatment for severe acute mitral regurgitation (MR) secondary to MI in surgical noncandidates, even when accompanied by cardiogenic shock, according to data from the international IREMMI registry.
“Cardiogenic shock, when adequately supported, does not seem to influence short- and mid-term outcomes, so the development of cardiogenic shock should not preclude percutaneous mitral valve repair in this scenario,” Rodrigo Estevez-Loureiro, MD, PhD, said in presenting the IREMMI (International Registry of MitraClip in Acute Myocardial Infarction) findings reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
Commentators hailed the prospective IREMMI data as potentially practice changing in light of the dire prognosis of such patients when surgery is deemed unacceptably high risk because medical management, the traditionally the only alternative, has a 30-day mortality of up to 50%.
Severe acute MR occurs in an estimated 3% of acute MIs, and in roughly 10% of patients who present with acute MI complicated by cardiogenic shock (CS). The impact of intervening with the MitraClip in an effort to correct the acute MR arising from MI with CS has previously been addressed only in sparse case reports. The new IREMMI study is easily the largest dataset to date detailing clinical and echocardiographic outcomes, Dr. Estevez-Loureiro of Alvaro Cunqueiro Hospital in Vigo, Spain, said at the meeting, sponsored by the Cardiovascular Research Foundation.
He reported on 93 consecutive patients who underwent MitraClip implantation for acute MR arising in the setting of MI, including 50 patients in CS at the time of the procedure. All 93 patients had been turned down by their surgical team because of extreme surgical risk. Three-quarters of the MIs showed ST-segment elevation. Only six patients had a papillary muscle rupture; in the rest, the mechanism of acute MR involved left ventricular global remodeling associated with mitral valve leaflet tethering. Percutaneous valve repair was performed at 18 expert valvular heart centers in the United States, Canada, Israel, and five European countries.
Procedural success
Time from MI to MitraClip implantation averaged 24 days in the CS patients and 33 days in the comparator arm without CS.
“These patients had been turned down for surgery, so the attending physicians generally followed a strategy of trying to cool them down with mechanical circulatory support and vasopressors. MitraClip wasn’t an option at the beginning, but after two or three failed weanings from all the possible therapies, then MitraClip becomes an option. This is one of the reasons why the time lapse between MI and the clip is so large,” the cardiologist explained.
Procedural success rates were similar in the two groups: 90% in those with CS and 93% in those without. However, average procedure time was significantly longer in the CS patients: 143 minutes versus 83 minutes in the patients without CS.
At baseline, 86% of the CS group had grade 4+ MR, similar to the 79% rate in the non-CS patients. Postprocedurally, 60% of the CS group were MR grade 0/1 and 34% were grade 2, comparable to the rates of 65% and 23% in the non-CS group.
At 3 months’ follow-up, 83.4% of the CS group had MR grade 2 or less, again not significantly different from the 90.5% rate in non-CS patients. Systolic pulmonary artery pressure was also similar: 39.6 mm Hg in the CS patients, 44 mm Hg in those without. While everyone was New York Heart Association functional class IV preprocedurally, 79.5% of the CS group were NYHA class I or II at 3 months, not significantly different from the 86.5% prevalence in the comparator arm.
Longer-term clinical outcomes
At a median follow-up of 7 months, the composite primary clinical outcome composed of all-cause mortality or heart failure rehospitalization did not differ between the two groups: a 28% rate in the CS group and 25.6% in non-CS patients. All-cause mortality occurred in 16% with CS and 9.3% without, again not a significant difference.
In a Cox regression analysis, neither surgical risk score, patient age, left ventricular geometry, nor CS was independently associated with the primary composite endpoint. Indeed, the only independent predictor of freedom from mortality or heart failure readmission at follow-up was procedural success, which is very much a function of the experience of the heart team, Dr. Estevez-Loureiro continued.
Michael A. Borger, MD, PhD, who comoderated the late-breaking clinical science session, was wowed by the IREMMI results.
“The mortality rates, I can tell you, compared to traditional surgical series of acute MR in the face of ACS [acute cardiogenic shock] are very, very respectable,” commented Dr. Borger, director of the cardiac surgery clinic at the Leipzig (Ger.) University Heart Center.
“Extremely impressive,” agreed discussant Vinayak N. Bapat, MD, a cardiothoracic surgeon and valve scientist at the Minneapolis Heart Institute Foundation. He posed a practical question: “Should we take from this presentation that patients should be stabilized with something like ECMO [extracorporeal membrane oxygenation] or Impella [left ventricular assist device], then transferred to an expert center for the procedure?”
“I think that the stabilization is essential in the patients with cardiogenic shock,” Dr. Estevez-Loureiro replied. “Unlike with surgery, it’s very difficult to establish a MitraClip procedure in a couple of hours in the middle of the night. You have to stabilize them and then treat for shock with ECMO, Impella, or both. I think they should be transferred to a center than can deliver the best treatment. In centers with less experience, patients can be put on mechanical support and transferred to an expert valve center, not only for MitraClip implantation, but for discussion of all the treatment possibilities, including surgery.”
At a press conference in which Dr. Estevez-Loureiro presented highlights of the IREMMI study, discussant Dee Dee Wang, MD, said the international coinvestigators “need to be applauded” for this study.
“Having these outcomes is incredible,” declared Dr. Wang, a structural heart disease specialist at the Henry Ford Health System, Detroit.
While this is an observational study, it’s a high-quality dataset with excellent methodology. And conducting a randomized trial in patients with such high surgical risk scores – the CS group had an average EuroSCORE II of 21 – would be extremely difficult, according to the cardiologist.
Dr. Estevez-Loureiro reported receiving research grants from Abbott and serving as a consultant to that company as well as Boston Scientific.
SOURCE: Estevez-Loureiro, R. TCT 2020, LBCS session IV.
FROM TCT 2020
Intravascular lithotripsy hailed as ‘game changer’ for coronary calcification
aimed at gaining U.S. regulatory approval.
The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.
Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.
Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.
“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.
Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.
This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.
Key outcomes
The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.
The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.
The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm2.
Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.
At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.
Outcomes were similar for the first case done at each participating center and all cases thereafter.
“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
The reaction
At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.
“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.
Cardiologists “really don’t do a good job most of the time” with severely calcified coronary lesions, added Dr. Jeremias, who wasn’t involved in the trial.
“A lot of times these patients have inadequate stent outcomes when we do intravascular imaging. So to do something to try to basically crack the calcium and expand the stent is, I think, critically important in these patients, and this is an amazing technology that accomplishes that,” the cardiologist said.
Juan F. Granada, MD, of Columbia University, New York, who moderated the press conference, said, “Some of the debulking techniques used for calcified stenoses actually require a lot of training, knowledge, experience, and hospital infrastructure.
I really think having a technology that is easy to use and familiar to all interventional cardiologists, such as a balloon, could potentially be a disruptive change in our field.”
“It’s an absolute game changer,” agreed Dr. Jeremias.
Dr. Kereiakes reported serving as a consultant to a handful of medical device companies, including Shockwave Medical, which sponsored Disrupt CAD III.
SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.
aimed at gaining U.S. regulatory approval.
The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.
Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.
Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.
“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.
Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.
This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.
Key outcomes
The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.
The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.
The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm2.
Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.
At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.
Outcomes were similar for the first case done at each participating center and all cases thereafter.
“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
The reaction
At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.
“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.
Cardiologists “really don’t do a good job most of the time” with severely calcified coronary lesions, added Dr. Jeremias, who wasn’t involved in the trial.
“A lot of times these patients have inadequate stent outcomes when we do intravascular imaging. So to do something to try to basically crack the calcium and expand the stent is, I think, critically important in these patients, and this is an amazing technology that accomplishes that,” the cardiologist said.
Juan F. Granada, MD, of Columbia University, New York, who moderated the press conference, said, “Some of the debulking techniques used for calcified stenoses actually require a lot of training, knowledge, experience, and hospital infrastructure.
I really think having a technology that is easy to use and familiar to all interventional cardiologists, such as a balloon, could potentially be a disruptive change in our field.”
“It’s an absolute game changer,” agreed Dr. Jeremias.
Dr. Kereiakes reported serving as a consultant to a handful of medical device companies, including Shockwave Medical, which sponsored Disrupt CAD III.
SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.
aimed at gaining U.S. regulatory approval.
The technology is basically the same as in extracorporeal lithotripsy, used for the treatment of kidney stones for more than 30 years: namely, transmission of pulsed acoustic pressure waves in order to fracture calcium. For interventional cardiology purposes, however, the transmitter is located within a balloon angioplasty catheter, Dean J. Kereiakes, MD, explained in presenting the study results at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
In Disrupt CAD III, intravascular lithotripsy far exceeded the procedural success and 30-day freedom from major adverse cardiovascular event (MACE) performance targets set in conjunction with the Food and Drug Administration. In so doing, the intravascular lithotripsy device developed by Shockwave Medical successfully addressed one of the banes of contemporary interventional cardiology: heavily calcified coronary lesions.
Currently available technologies targeting such lesions, including noncompliant high-pressure balloons, intravascular lasers, cutting balloons, and orbital and rotational atherectomy, often yield suboptimal results, noted Dr. Kereiakes, medical director of the Christ Hospital Heart and Cardiovascular Center in Cincinnati.
Severe vascular calcifications are becoming more common, due in part to an aging population and the growing prevalence of hypertension, diabetes, and renal insufficiency. Severely calcified coronary lesions complicate percutaneous coronary intervention. They’re associated with increased risks of dissection, perforation, and periprocedural MI. Moreover, heavily calcified lesions impede stent delivery and expansion – and stent underexpansion is the leading predictor of restenosis and stent thrombosis, he observed at the meeting, sponsored by the Cardiovascular Research Foundation. Disrupt CAD III was a prospective single-arm study of 384 patients at 47 sites in the United States and several European countries. All participants had de novo coronary calcifications graded as severe by core laboratory assessment, with a mean calcified length of 47.9 mm by quantitative coronary angiography and a mean calcium angle and thickness of 292.5 degrees and 0.96 mm by optical coherence tomography.
“It’s staggering, the level of calcification these patients had. It’s jaw dropping,” Dr. Kereiakes observed.
Intravascular lithotripsy was used to prepare these severely calcified lesions for stenting. The intervention entailed transmission of acoustic waves circumferentially and transmurally at 1 pulse per second through tissue at an effective pressure of about 50 atm. Patients received an average of 69 pulses.
This was not a randomized trial; there was no sham-treated control arm. Instead, the comparator group selected under regulatory guidance was comprised of patients who had received orbital atherectomy for severe coronary calcifications in the earlier, similarly designed ORBIT II trial, which led to FDA marketing approval of that technology.
Key outcomes
The procedural success rate, defined as successful stent delivery with less than a 50% residual stenosis and no in-hospital MACE, was 92.4% in Disrupt CAD III, compared to 83.4% for orbital atherectomy in ORBIT II. The primary safety endpoint of freedom from cardiac death, MI, or target vessel revascularization at 30 days was achieved in 92.2% of patients in the intravascular lithotripsy trial, versus 84.4% in ORBIT II.
The 30-day MACE rate of 7.8% in Disrupt CAD III was primarily driven by periprocedural MIs, which occurred in 6.8% of participants. Only one-third of the MIs were clinically relevant by the Society for Coronary Angiography and Intervention definition. There were two cardiac deaths and three cases of stent thrombosis, all of which were associated with known predictors of the complication. There was 1 case each of dissection, abrupt closure, and perforation, but no instances of slow flow or no reflow at the procedure’s end. Transient lithotripsy-induced left ventricular capture occurred in 41% of patients, but they were benign events with no lasting consequences.
The device was able to cross and deliver acoustic pressure wave therapy to 98.2% of lesions. The mean diameter stenosis preprocedure was 65.1%, dropping to 37.2% post lithotripsy, with a final in-stent residual stenosis diameter of 11.9%, with a 1.7-mm acute gain. The average stent expansion at the site of maximum calcification was 102%, with a minimum stent area of 6.5 mm2.
Optical coherence imaging revealed that 67% of treated lesions had circumferential and transmural fractures of both deep and superficial calcium post lithotripsy. Yet outcomes were the same regardless of whether fractures were evident on imaging.
At 30-day follow-up, 72.9% of patients had no angina, up from just 12.6% of participants pre-PCI. Follow-up will continue for 2 years.
Outcomes were similar for the first case done at each participating center and all cases thereafter.
“The ease of use was remarkable,” Dr. Kereiakes recalled. “The learning curve is virtually nonexistent.”
The reaction
At a press conference where Dr. Kereiakes presented the Disrupt CAD III results, discussant Allen Jeremias, MD, said he found the results compelling.
“The success rate is high, I think it’s relatively easy to use, as demonstrated, and I think the results are spectacular,” said Dr. Jeremias, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.
Cardiologists “really don’t do a good job most of the time” with severely calcified coronary lesions, added Dr. Jeremias, who wasn’t involved in the trial.
“A lot of times these patients have inadequate stent outcomes when we do intravascular imaging. So to do something to try to basically crack the calcium and expand the stent is, I think, critically important in these patients, and this is an amazing technology that accomplishes that,” the cardiologist said.
Juan F. Granada, MD, of Columbia University, New York, who moderated the press conference, said, “Some of the debulking techniques used for calcified stenoses actually require a lot of training, knowledge, experience, and hospital infrastructure.
I really think having a technology that is easy to use and familiar to all interventional cardiologists, such as a balloon, could potentially be a disruptive change in our field.”
“It’s an absolute game changer,” agreed Dr. Jeremias.
Dr. Kereiakes reported serving as a consultant to a handful of medical device companies, including Shockwave Medical, which sponsored Disrupt CAD III.
SOURCE: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.
FROM TCT 2020
Key clinical point: Intravascular lithotripsy was safe and effective for treatment of severely calcified coronary stenoses in a pivotal trial.
Major finding: The 30-day rate of freedom from major adverse cardiovascular events was 92.2%, well above the prespecified performance goal of 84.4%.
Study details: Disrupt CAD III study is a multicenter, single-arm, prospective study of intravascular lithotripsy in 384 patients with severe coronary calcification.
Disclosures: The presenter reported serving as a consultant to Shockwave Medical Inc., the study sponsor, as well as several other medical device companies.
Source: Kereiakes DJ. TCT 2020. Late Breaking Clinical Science session 2.
NACMI: Clear benefit with PCI in STEMI COVID-19 patients
Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).
Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).
“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.
The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.
Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.
NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.
The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.
Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.
The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.
COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).
They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.
Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.
Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).
But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).
Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.
“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”
Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.
During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.
“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”
Future topics of interest include ethnic and regional/country differences; time-to-treatment including chest pain onset-to-arrival; transfer, in-hospital, and no-culprit patients; changes over time during the pandemic; and eventually 1-year outcomes, Dr. Henry said.
Press briefing moderator Ajay Kirtane, MD, director of the cardiac catheterization labs at NewYork-Presbyterian/Columbia University Irving, New York, remarked that “a lot of times people will pooh-pooh observational data, but this is exactly the type of data that we need to try to be able to gather information about what our practices are, how they fit. And I think many of us around the world will see these data, and it will echo their own experience.”
The study was funded by the Society for Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology. Dr. Henry has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).
Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).
“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.
The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.
Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.
NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.
The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.
Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.
The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.
COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).
They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.
Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.
Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).
But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).
Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.
“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”
Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.
During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.
“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”
Future topics of interest include ethnic and regional/country differences; time-to-treatment including chest pain onset-to-arrival; transfer, in-hospital, and no-culprit patients; changes over time during the pandemic; and eventually 1-year outcomes, Dr. Henry said.
Press briefing moderator Ajay Kirtane, MD, director of the cardiac catheterization labs at NewYork-Presbyterian/Columbia University Irving, New York, remarked that “a lot of times people will pooh-pooh observational data, but this is exactly the type of data that we need to try to be able to gather information about what our practices are, how they fit. And I think many of us around the world will see these data, and it will echo their own experience.”
The study was funded by the Society for Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology. Dr. Henry has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).
Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).
“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.
The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.
Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.
NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.
The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.
Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.
The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.
COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).
They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.
Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.
Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).
But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).
Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.
“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”
Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.
During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.
“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”
Future topics of interest include ethnic and regional/country differences; time-to-treatment including chest pain onset-to-arrival; transfer, in-hospital, and no-culprit patients; changes over time during the pandemic; and eventually 1-year outcomes, Dr. Henry said.
Press briefing moderator Ajay Kirtane, MD, director of the cardiac catheterization labs at NewYork-Presbyterian/Columbia University Irving, New York, remarked that “a lot of times people will pooh-pooh observational data, but this is exactly the type of data that we need to try to be able to gather information about what our practices are, how they fit. And I think many of us around the world will see these data, and it will echo their own experience.”
The study was funded by the Society for Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology. Dr. Henry has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Ticagrelor monotherapy beats DAPT in STEMI
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
, a major randomized trial.
“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).
TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).
The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.
Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.
In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.
Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.
“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.
Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.
“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.
“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.
“From a clinical standpoint, this strategy seems particularly appealing in high bleeding risk patients,” the cardiologist concluded at the at the meeting, which was sponsored by the Cardiovascular Research Foundation.
He added, however, that the TICO-STEMI data with respect to complex PCI “are not really reassuring and are probably worth another investigation.”
Dr. Kim reported having no financial conflicts regarding the TICO-STEMI trial, funded by Biotronik.
AT TCT 2020
Benefit of rivaroxaban after limb revascularization greatest in those with comorbid CAD
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.
“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.
VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.
Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.
In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.
“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”
Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.
In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.
Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.
VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.
FROM ESC CONGRESS 2020
Dapagliflozin’s CKD performance sends heart failure messages
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.
Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
What DAPA-CKD means for heart failure
The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.
Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.
The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”
The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m2; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m2.
“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
DAPA-CKD grows the pool of eligible heart failure patients
A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.
Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.
In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
New DAPA-HF results show no drug, device interactions
In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.
Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.
DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.
FROM HFSA 2020
AHA scientific statement highlights cardiorenal benefit of new diabetes drugs
To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.
Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.
The scientific statement was published online Sept. 28 in Circulation.
“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.
“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.
“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
Recommendations at a glance
- Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
- Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
- Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
- Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
- Monitor and control high blood pressure.
- Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
- Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.
The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
Collaborative care model
The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.
There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.
But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.
For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.
Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.
“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”
Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.
A version of this article originally appeared on Medscape.com .
To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.
Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.
The scientific statement was published online Sept. 28 in Circulation.
“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.
“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.
“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
Recommendations at a glance
- Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
- Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
- Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
- Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
- Monitor and control high blood pressure.
- Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
- Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.
The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
Collaborative care model
The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.
There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.
But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.
For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.
Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.
“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”
Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.
A version of this article originally appeared on Medscape.com .
To protect the heart and kidneys, sodium-glucose transporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) receptor agonists should be considered for people with type 2 diabetes and chronic kidney disease (CKD), the American Heart Association advised in a new scientific statement.
Taken together, the results of relevant clinical trials indicate that SGLT2 inhibitors and GLP-1 receptor agonists safely and significantly reduce the risk for cardiovascular (CV) events, death, and the slow progression of CKD to end-stage kidney disease, including the risks for dialysis, transplantation, and death, the writing group says.
The scientific statement was published online Sept. 28 in Circulation.
“There has been rapid reporting of high-quality data in the cardio-renal-metabolic space with significant heart and kidney benefits, particularly with these two newer classes of antihyperglycemic agents,” Janani Rangaswami, MD, who chaired the writing group, said in an interview.
“More recent data show benefits in chronic kidney disease and heart failure even in patients without diabetes,” said Dr. Rangaswami, Einstein Medical Center and Sidney Kimmel Medical College, both in Philadelphia.
“These data are practice-changing in both cardiology and nephrology, and usher in a new era of disease-modifying therapies in heart and kidney disease,” Dr. Rangaswami added.
Recommendations at a glance
- Provide early and ongoing assessment of risks for CVD and CKD to patients who may benefit from SGLT2 inhibitors of GLP-1 receptor agonists.
- Tailor medication choices that meet the needs of individual patients. Realize that, given “consistent class-wide effects,” the choice of a specific SGLT2 inhibitor or GLP-1 receptor agonist may be dictated by affordability, coverage, and formulary considerations.
- Adjust all medications in tandem with these medicines and consider the burden of polypharmacy, which is common among people with type 2 diabetes. Adjust concomitant therapies and deprescribe where possible.
- Identify risks for hypoglycemia and educate patients on the signs so they can seek treatment quickly.
- Monitor and control high blood pressure.
- Counsel patients about the risks for and symptoms of euglycemic diabetic ketoacidosis when taking SGLT2 inhibitors, as well as classic DKA, which can be fatal.
- Regularly screen and counsel patients about foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.
The writing group identified two additional patient subgroups that may benefit from SGLT2 inhibitors and GLP-1 receptor agonists: those with heart failure with reduced ejection fraction with or without diabetes; and those with CKD who do not have diabetes. They say more data are anticipated to validate the use of SGLT2 inhibitors and GLP-1 receptor agonists in these “at-risk” patients.
Collaborative care model
The writing group proposed a collaborative care model, bridging cardiologists, nephrologists, endocrinologists, and primary care physicians, to help facilitate the “prompt and appropriate” integration of these new classes of medications in the management of patients with type 2 diabetes and CKD.
There is “an unmet need for a cardio-renal-metabolic care model that incorporates best practices in the real world to help align these therapies, especially with vulnerable high-risk patients with cardiorenal disease, and to overcome barriers toward uptake of these agents. Hopefully this statement provides some guidance to the cardiology and nephrology communities in that area,” Dr. Rangaswami said in an interview.
But old habits die hard, as research continues to show the slow adoption of these newer medications in the real world.
For example, a large observational study published last year showed a “striking” discordance between evidence-based, guideline-recommended use of SGLT2 inhibitors for the treatment of type 2 diabetes and their actual uptake in clinical practice.
Paradoxically, patients with CVD, heart failure, hypertension, CKD, and those at risk for hypoglycemia were less apt to receive an SGLT2 inhibitor than other patients.
“The relatively slow uptake of these agents is multifactorial,” Dr. Rangaswami said. “Cardiologists and nephrologists may suffer from some level of ‘therapeutic inertia’ when using new agents they are unfamiliar with and originally branded as ‘antidiabetic’ agents, with the perception of these agents being outside the scope of their practice.”
Two other factors are also at play. “The current health care system is based on ‘specialty silos,’ where specialists tend to stick to the traditional scope of their specialty and are reluctant to view these agents as part of their therapeutic armamentarium. Finally, insurance coverage barriers and affordability also limit the use on a widespread basis,” Dr. Rangaswami said.
A version of this article originally appeared on Medscape.com .
Nationwide study questions routine long-term beta-blocker post MI
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
FROM ESC CONGRESS 2020