Cardiology News

The Chinese Society of Cardiology (CSC) has issued a consensus statement on the management of cardiac emergencies during the COVID-19 pandemic.

The document first appeared in the Chinese Journal of Cardiology, and a translated version was published in Circulation. The consensus statement was developed by 125 medical experts in the fields of cardiovascular disease and infectious disease. This included 23 experts currently working in Wuhan, China.

Three overarching principles guided their recommendations.

• The highest priority is prevention and control of transmission (including protecting staff).
• Patients should be assessed both for COVID-19 and for cardiovascular issues.
• At all times, all interventions and therapies provided should be in concordance with directives of infection control authorities.

“Considering that some asymptomatic patients may be a source of infection and transmission, all patients with severe emergent cardiovascular diseases should be managed as suspected cases of COVID-19 in Hubei Province,” noted writing chair and cardiologist Yaling Han, MD, of the General Hospital of Northern Theater Command in Shenyang, China.

In areas outside Hubei Province, where COVID-19 was less prevalent, this “infected until proven otherwise” approach was also recommended, although not as strictly.

Diagnosing CVD and COVID-19 simultaneously

In patients with emergent cardiovascular needs in whom COVID-19 has not been ruled out, quarantine in a single-bed room is needed, they wrote. The patient should be monitored for clinical manifestations of the disease, and undergo COVID-19 nucleic acid testing as soon as possible.

After infection control is considered, including limiting risk for infection to health care workers, risk assessment that weighs the relative advantages and disadvantages of treating the cardiovascular disease while preventing transmission can be considered, the investigators wrote.

At all times, transfers to different areas of the hospital and between hospitals should be minimized to reduce the risk for infection transmission.

The authors also recommended the use of “select laboratory tests with definitive sensitivity and specificity for disease diagnosis or assessment.”

For patients with acute aortic syndrome or acute pulmonary embolism, this means CT angiography. When acute pulmonary embolism is suspected, D-dimer testing and deep vein ultrasound can be employed, and for patients with acute coronary syndrome, ordinary electrocardiography and standard biomarkers for cardiac injury are preferred.

In addition, “all patients should undergo lung CT examination to evaluate for imaging features typical of COVID-19. ... Chest x-ray is not recommended because of a high rate of false negative diagnosis,” the authors wrote.

Intervene with caution

Medical therapy should be optimized in patients with emergent cardiovascular issues, with invasive strategies for diagnosis and therapy used “with caution,” according to the Chinese experts.

Conditions for which conservative medical treatment is recommended during COVID-19 pandemic include ST-segment elevation MI (STEMI) where thrombolytic therapy is indicated, STEMI when the optimal window for revascularization has passed, high-risk non-STEMI (NSTEMI), patients with uncomplicated Stanford type B aortic dissection, acute pulmonary embolism, acute exacerbation of heart failure, and hypertensive emergency.

“Vigilance should be paid to avoid misdiagnosing patients with pulmonary infarction as COVID-19 pneumonia,” they noted.

Diagnoses warranting invasive intervention are limited to STEMI with hemodynamic instability, life-threatening NSTEMI, Stanford type A or complex type B acute aortic dissection, bradyarrhythmia complicated by syncope or unstable hemodynamics mandating implantation of a device, and pulmonary embolism with hemodynamic instability for whom intravenous thrombolytics are too risky.

Interventions should be done in a cath lab or operating room with negative-pressure ventilation, with strict periprocedural disinfection. Personal protective equipment should also be of the strictest level.

In patients for whom COVID-19 cannot be ruled out presenting in a region with low incidence of COVID-19, interventions should only be considered for more severe cases and undertaken in a cath lab, electrophysiology lab, or operating room “with more than standard disinfection procedures that fulfill regulatory mandates for infection control.”

If negative-pressure ventilation is not available, air conditioning (for example, laminar flow and ventilation) should be stopped.

Establish plans now

“We operationalized all of these strategies at Beth Israel Deaconess Medical Center several weeks ago, since Boston had that early outbreak with the Biogen conference, but I suspect many institutions nationally are still formulating plans,” said Dhruv Kazi, MD, MSc, in an interview.

Although COVID-19 is “primarily a single-organ disease – it destroys the lungs” – transmission of infection to cardiology providers was an early problem that needed to be addressed, said Dr. Kazi. “We now know that a cardiologist seeing a patient who reports shortness of breath and then leans in to carefully auscultate the lungs and heart can get exposed if not provided adequate personal protective equipment; hence the cancellation of elective procedures, conversion of most elective visits to telemedicine, if possible, and the use of surgical/N95 masks in clinic and on rounds.”

Regarding the CSC recommendation to consider medical over invasive management, Dr. Kazi noteed that this works better in a setting where rapid testing is available. “Where that is not the case – as in the U.S. – resorting to conservative therapy for all COVID suspect cases will result in suboptimal care, particularly when nine out of every 10 COVID suspects will eventually rule out.”

One of his biggest worries now is that patients simply won’t come. Afraid of being exposed to COVID-19, patients with MIs and strokes may avoid or delay coming to the hospital.

“There is some evidence that this occurred in Wuhan, and I’m starting to see anecdotal evidence of this in Boston,” said Dr. Kazi. “We need to remind our patients that, if they experience symptoms of a heart attack or stroke, they deserve the same lifesaving treatment we offered before this pandemic set in. They should not try and sit it out.”

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

The Chinese Society of Cardiology (CSC) has issued a consensus statement on the management of cardiac emergencies during the COVID-19 pandemic.

The document first appeared in the Chinese Journal of Cardiology, and a translated version was published in Circulation. The consensus statement was developed by 125 medical experts in the fields of cardiovascular disease and infectious disease. This included 23 experts currently working in Wuhan, China.

Three overarching principles guided their recommendations.

• The highest priority is prevention and control of transmission (including protecting staff).
• Patients should be assessed both for COVID-19 and for cardiovascular issues.
• At all times, all interventions and therapies provided should be in concordance with directives of infection control authorities.

“Considering that some asymptomatic patients may be a source of infection and transmission, all patients with severe emergent cardiovascular diseases should be managed as suspected cases of COVID-19 in Hubei Province,” noted writing chair and cardiologist Yaling Han, MD, of the General Hospital of Northern Theater Command in Shenyang, China.

In areas outside Hubei Province, where COVID-19 was less prevalent, this “infected until proven otherwise” approach was also recommended, although not as strictly.

Diagnosing CVD and COVID-19 simultaneously

In patients with emergent cardiovascular needs in whom COVID-19 has not been ruled out, quarantine in a single-bed room is needed, they wrote. The patient should be monitored for clinical manifestations of the disease, and undergo COVID-19 nucleic acid testing as soon as possible.

After infection control is considered, including limiting risk for infection to health care workers, risk assessment that weighs the relative advantages and disadvantages of treating the cardiovascular disease while preventing transmission can be considered, the investigators wrote.

At all times, transfers to different areas of the hospital and between hospitals should be minimized to reduce the risk for infection transmission.

The authors also recommended the use of “select laboratory tests with definitive sensitivity and specificity for disease diagnosis or assessment.”

For patients with acute aortic syndrome or acute pulmonary embolism, this means CT angiography. When acute pulmonary embolism is suspected, D-dimer testing and deep vein ultrasound can be employed, and for patients with acute coronary syndrome, ordinary electrocardiography and standard biomarkers for cardiac injury are preferred.

In addition, “all patients should undergo lung CT examination to evaluate for imaging features typical of COVID-19. ... Chest x-ray is not recommended because of a high rate of false negative diagnosis,” the authors wrote.

Intervene with caution

Medical therapy should be optimized in patients with emergent cardiovascular issues, with invasive strategies for diagnosis and therapy used “with caution,” according to the Chinese experts.

Conditions for which conservative medical treatment is recommended during COVID-19 pandemic include ST-segment elevation MI (STEMI) where thrombolytic therapy is indicated, STEMI when the optimal window for revascularization has passed, high-risk non-STEMI (NSTEMI), patients with uncomplicated Stanford type B aortic dissection, acute pulmonary embolism, acute exacerbation of heart failure, and hypertensive emergency.

“Vigilance should be paid to avoid misdiagnosing patients with pulmonary infarction as COVID-19 pneumonia,” they noted.

Diagnoses warranting invasive intervention are limited to STEMI with hemodynamic instability, life-threatening NSTEMI, Stanford type A or complex type B acute aortic dissection, bradyarrhythmia complicated by syncope or unstable hemodynamics mandating implantation of a device, and pulmonary embolism with hemodynamic instability for whom intravenous thrombolytics are too risky.

Interventions should be done in a cath lab or operating room with negative-pressure ventilation, with strict periprocedural disinfection. Personal protective equipment should also be of the strictest level.

In patients for whom COVID-19 cannot be ruled out presenting in a region with low incidence of COVID-19, interventions should only be considered for more severe cases and undertaken in a cath lab, electrophysiology lab, or operating room “with more than standard disinfection procedures that fulfill regulatory mandates for infection control.”

If negative-pressure ventilation is not available, air conditioning (for example, laminar flow and ventilation) should be stopped.

Establish plans now

“We operationalized all of these strategies at Beth Israel Deaconess Medical Center several weeks ago, since Boston had that early outbreak with the Biogen conference, but I suspect many institutions nationally are still formulating plans,” said Dhruv Kazi, MD, MSc, in an interview.

Although COVID-19 is “primarily a single-organ disease – it destroys the lungs” – transmission of infection to cardiology providers was an early problem that needed to be addressed, said Dr. Kazi. “We now know that a cardiologist seeing a patient who reports shortness of breath and then leans in to carefully auscultate the lungs and heart can get exposed if not provided adequate personal protective equipment; hence the cancellation of elective procedures, conversion of most elective visits to telemedicine, if possible, and the use of surgical/N95 masks in clinic and on rounds.”

Regarding the CSC recommendation to consider medical over invasive management, Dr. Kazi noteed that this works better in a setting where rapid testing is available. “Where that is not the case – as in the U.S. – resorting to conservative therapy for all COVID suspect cases will result in suboptimal care, particularly when nine out of every 10 COVID suspects will eventually rule out.”

One of his biggest worries now is that patients simply won’t come. Afraid of being exposed to COVID-19, patients with MIs and strokes may avoid or delay coming to the hospital.

“There is some evidence that this occurred in Wuhan, and I’m starting to see anecdotal evidence of this in Boston,” said Dr. Kazi. “We need to remind our patients that, if they experience symptoms of a heart attack or stroke, they deserve the same lifesaving treatment we offered before this pandemic set in. They should not try and sit it out.”

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

The Chinese Society of Cardiology (CSC) has issued a consensus statement on the management of cardiac emergencies during the COVID-19 pandemic.

The document first appeared in the Chinese Journal of Cardiology, and a translated version was published in Circulation. The consensus statement was developed by 125 medical experts in the fields of cardiovascular disease and infectious disease. This included 23 experts currently working in Wuhan, China.

Three overarching principles guided their recommendations.

• The highest priority is prevention and control of transmission (including protecting staff).
• Patients should be assessed both for COVID-19 and for cardiovascular issues.
• At all times, all interventions and therapies provided should be in concordance with directives of infection control authorities.

“Considering that some asymptomatic patients may be a source of infection and transmission, all patients with severe emergent cardiovascular diseases should be managed as suspected cases of COVID-19 in Hubei Province,” noted writing chair and cardiologist Yaling Han, MD, of the General Hospital of Northern Theater Command in Shenyang, China.

In areas outside Hubei Province, where COVID-19 was less prevalent, this “infected until proven otherwise” approach was also recommended, although not as strictly.

Diagnosing CVD and COVID-19 simultaneously

In patients with emergent cardiovascular needs in whom COVID-19 has not been ruled out, quarantine in a single-bed room is needed, they wrote. The patient should be monitored for clinical manifestations of the disease, and undergo COVID-19 nucleic acid testing as soon as possible.

After infection control is considered, including limiting risk for infection to health care workers, risk assessment that weighs the relative advantages and disadvantages of treating the cardiovascular disease while preventing transmission can be considered, the investigators wrote.

At all times, transfers to different areas of the hospital and between hospitals should be minimized to reduce the risk for infection transmission.

The authors also recommended the use of “select laboratory tests with definitive sensitivity and specificity for disease diagnosis or assessment.”

For patients with acute aortic syndrome or acute pulmonary embolism, this means CT angiography. When acute pulmonary embolism is suspected, D-dimer testing and deep vein ultrasound can be employed, and for patients with acute coronary syndrome, ordinary electrocardiography and standard biomarkers for cardiac injury are preferred.

In addition, “all patients should undergo lung CT examination to evaluate for imaging features typical of COVID-19. ... Chest x-ray is not recommended because of a high rate of false negative diagnosis,” the authors wrote.

Intervene with caution

Medical therapy should be optimized in patients with emergent cardiovascular issues, with invasive strategies for diagnosis and therapy used “with caution,” according to the Chinese experts.

Conditions for which conservative medical treatment is recommended during COVID-19 pandemic include ST-segment elevation MI (STEMI) where thrombolytic therapy is indicated, STEMI when the optimal window for revascularization has passed, high-risk non-STEMI (NSTEMI), patients with uncomplicated Stanford type B aortic dissection, acute pulmonary embolism, acute exacerbation of heart failure, and hypertensive emergency.

“Vigilance should be paid to avoid misdiagnosing patients with pulmonary infarction as COVID-19 pneumonia,” they noted.

Diagnoses warranting invasive intervention are limited to STEMI with hemodynamic instability, life-threatening NSTEMI, Stanford type A or complex type B acute aortic dissection, bradyarrhythmia complicated by syncope or unstable hemodynamics mandating implantation of a device, and pulmonary embolism with hemodynamic instability for whom intravenous thrombolytics are too risky.

Interventions should be done in a cath lab or operating room with negative-pressure ventilation, with strict periprocedural disinfection. Personal protective equipment should also be of the strictest level.

In patients for whom COVID-19 cannot be ruled out presenting in a region with low incidence of COVID-19, interventions should only be considered for more severe cases and undertaken in a cath lab, electrophysiology lab, or operating room “with more than standard disinfection procedures that fulfill regulatory mandates for infection control.”

If negative-pressure ventilation is not available, air conditioning (for example, laminar flow and ventilation) should be stopped.

Establish plans now

“We operationalized all of these strategies at Beth Israel Deaconess Medical Center several weeks ago, since Boston had that early outbreak with the Biogen conference, but I suspect many institutions nationally are still formulating plans,” said Dhruv Kazi, MD, MSc, in an interview.

Although COVID-19 is “primarily a single-organ disease – it destroys the lungs” – transmission of infection to cardiology providers was an early problem that needed to be addressed, said Dr. Kazi. “We now know that a cardiologist seeing a patient who reports shortness of breath and then leans in to carefully auscultate the lungs and heart can get exposed if not provided adequate personal protective equipment; hence the cancellation of elective procedures, conversion of most elective visits to telemedicine, if possible, and the use of surgical/N95 masks in clinic and on rounds.”

Regarding the CSC recommendation to consider medical over invasive management, Dr. Kazi noteed that this works better in a setting where rapid testing is available. “Where that is not the case – as in the U.S. – resorting to conservative therapy for all COVID suspect cases will result in suboptimal care, particularly when nine out of every 10 COVID suspects will eventually rule out.”

One of his biggest worries now is that patients simply won’t come. Afraid of being exposed to COVID-19, patients with MIs and strokes may avoid or delay coming to the hospital.

“There is some evidence that this occurred in Wuhan, and I’m starting to see anecdotal evidence of this in Boston,” said Dr. Kazi. “We need to remind our patients that, if they experience symptoms of a heart attack or stroke, they deserve the same lifesaving treatment we offered before this pandemic set in. They should not try and sit it out.”

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

The Food and Drug Administration issued an Emergency Use Authorization on March 28, 2020, allowing for the usage of hydroxychloroquine sulfate and chloroquine phosphate products in certain hospitalized patients with COVID-19.

The products, currently stored by the Strategic National Stockpile, will be distributed by the SNS to states so that doctors may prescribe the drugs to adolescent and adult patients hospitalized with COVID-19 in the absence of appropriate or feasible clinical trials. The SNS will work with the Federal Emergency Management Agency to ship the products to states.

According to the Emergency Use Authorization, fact sheets will be provided to health care providers and patients with important information about hydroxychloroquine sulfate and chloroquine phosphate, including the risks of using them to treat COVID-19.

[email protected]

The Food and Drug Administration issued an Emergency Use Authorization on March 28, 2020, allowing for the usage of hydroxychloroquine sulfate and chloroquine phosphate products in certain hospitalized patients with COVID-19.

The products, currently stored by the Strategic National Stockpile, will be distributed by the SNS to states so that doctors may prescribe the drugs to adolescent and adult patients hospitalized with COVID-19 in the absence of appropriate or feasible clinical trials. The SNS will work with the Federal Emergency Management Agency to ship the products to states.

According to the Emergency Use Authorization, fact sheets will be provided to health care providers and patients with important information about hydroxychloroquine sulfate and chloroquine phosphate, including the risks of using them to treat COVID-19.

[email protected]

The Food and Drug Administration issued an Emergency Use Authorization on March 28, 2020, allowing for the usage of hydroxychloroquine sulfate and chloroquine phosphate products in certain hospitalized patients with COVID-19.

The products, currently stored by the Strategic National Stockpile, will be distributed by the SNS to states so that doctors may prescribe the drugs to adolescent and adult patients hospitalized with COVID-19 in the absence of appropriate or feasible clinical trials. The SNS will work with the Federal Emergency Management Agency to ship the products to states.

According to the Emergency Use Authorization, fact sheets will be provided to health care providers and patients with important information about hydroxychloroquine sulfate and chloroquine phosphate, including the risks of using them to treat COVID-19.

[email protected]

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

The guidelines allow for the addition of short-term clopidogrel to an oral anticoagulant (OAC) in patients with an established OAC indication, such as atrial fibrillation (AF), who undergo transcatheter aortic valve replacement (TAVR). But does the extra antithrombotic protection come with safety issues?

It apparently did in the POPULAR-TAVI trial, which saw an excess of major and minor bleeding in such patients already on an OAC when they underwent TAVR and who then took the antiplatelet agent for the next 3 months.

The patients who instead continued on their OAC as the only post-TAVR antithrombotic, compared with those on double therapy, showed a 37% lower 1-year risk of any bleeding, including major and disabling bleeding.

Importantly, they didn’t seem to pay a price in excess ischemic events, such as stroke or myocardial infarction (MI).

The trial argues against adding clopidogrel on top of OAC in TAVR patients with an OAC indication in order to reduce their risk of bleeding, Jurriën ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands, told theheart.org | Medscape Cardiology.

Whether the ischemic event risk was comparable with and without clopidogrel is less clear. “As the study is not powered for the ischemic end points, the answer is less definite. But we did not see a hint of a higher ischemic event rate, especially stroke, in the OAC-alone group,” ten Berg said.

“So we are pretty confident in saying that OAC alone is the optimal treatment.”

The results of POPULAR-TAVI were presented by Vincent Nijenhuis, MD, also from St. Antonius Hospital, on March 29 during the virtual presentation of the American College of Cardiology 2020 Scientific Session/World Congress of Cardiology. Nijenhuis is also first author on the trial’s simultaneous publication in the New England Journal of Medicine.

The only reason to add an antiplatelet in TAVR patients who need to be on an OAC for another indication is to prevent ischemic events like MI, stroke, or death, agreed George D. Dangas, MD, PhD, Mount Sinai Hospital, New York City, for theheart.org | Medscape Cardiology.

But that protection apparently wasn’t needed; for patients on OAC only, “the overall risk–benefit ratio was favorable for them both ways. Although the study is small, I think the findings would be clinically meaningful,” said Dangas, who was not involved in POPULAR-TAVI but was lead author on the GALILEO trial publication.

GALILEO tested a direct oral anticoagulant (DOAC) against dual antiplatelet therapy in patients undergoing TAVR but without a conventional OAC indication. The trial was halted because the DOAC group started to show an excess of bleeding, thromboembolic events, and mortality.

Most POPULAR-TAVI patients were on vitamin K antagonists, but about a quarter were taking DOACs. Clopidogrel was given on an open-label basis.

The trial suggests that, for TAVR patients with an indication for lifelong OAC, “it does appear to be safe to give only an anticoagulant, whether it’s warfarin or a DOAC, and not add clopidogrel,” Robert O. Bonow, MD, Northwestern University, Chicago, told theheart.org | Medscape Cardiology.

“The bottom line appears to be that it’s no worse, and is probably better in terms of bleeding events,” said Bonow, who wasn’t involved in POPULAR-TAVI.

But there are difficulties in interpreting the trial that stem from its design and other issues, he said. For example, it can’t really be concluded that adding an antiplatelet agent to OAC in such patients who undergo TAVR, according to commonly practiced techniques, will increase the risk of bleeding compared with OAC alone.

To begin with, Bonow said, substituting aspirin for clopidogrel might have produced better double-therapy results. But the bigger issues, Bonow said, center on the discretion its operators had in whether to maintain or suspend the patients’ OAC during the TAVR procedure, as well as the unusual bleeding definitions used in the trial.

The first POPULAR-TAVI primary end point was any bleeding that met Valve Academic Research Consortium (VARC) criteria; the second was nonprocedural bleeding that met the Bleeding Academic Research Consortium (BARC) definition.

“Because the VARC-2 classification does not distinguish between procedure-related and nonprocedure-related bleeding events, procedure-related events were defined as BARC type 4 severe bleeding,” the trial’s journal report states. Therefore, “most bleeding at the puncture site was counted as nonprocedure-related.”

It may be Bonow’s biggest issue with the trial, he said. “They’re terming these events that occurred periprocedurally, in the first day or first hours of the procedure, as being ‘nonprocedural’ because they didn’t represent severe BARC bleeding, where you have a subarachnoid hemorrhage or require transfusions.”

An editorial accompanying the trial report also knocks this aspect of the trial design. Although the trial “confirmed” a higher incidence of any bleeding in the double-therapy group, “there are concerns regarding the classification of bleeding and the reliability of secondary outcome analysis,” writes Frederick Feit, MD, NYU Grossman School of Medicine, New York City.

“Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure related, even if it occurred at the access site,” the editorial notes.

Ten Berg noted that procedural bleeding is frequent in TAVI, but the VARC-2 definition doesn’t accommodate them. So “we also used the BARC definition for procedural bleeding, BARC-4,” he told theheart.org | Medscape Cardiology.

“However, BARC-4 describes bleeding during surgery, and it turned out that in POPULAR- TAVI only one patient had BARC-4 bleeding. So we do not at all agree with the editorial.”

Still, the trial’s reported event-rate curves show that “most of the step-up in bleeding, in either arm of the trial, occurred immediately,” Bonow observed. A more consistent, flat trend followed thereafter out to 3 months.

“So half of the bleeding in both arms of the trial occurred at the site of the arterial puncture. Though it wasn’t considered severe, it was indeed periprocedural,” Bonow said, interpreting the results.

The POPULAR-TAVI journal report says the procedures were performed according to local site protocols, and site physicians were allowed to decide whether to continue or suspend OAC. But “the trial protocol advised physicians to continue oral anticoagulation during admission for the TAVI procedure.”

Many of the patients, regardless of randomization group, “went through the procedure under full anticoagulation,” Dangas agreed. POPULAR-TAVI, it seems, “is the first anticoagulation study ever to start anticoagulation before the procedure.”

Bleeding event rates in the trial “are somewhat high because of this unusual procedural feature of the study,” Dangas said.

“It’s therefore not surprising that so much of the bleeding occurred in the first hours of the procedure itself,” observed Bonow.

The trial enrolled 313 patients in four European countries who were on OAC for an approved indication, predominantly AF, and underwent TAVR. Their mean age was about 81 years, and 45.4% were women. They were randomly assigned to receive or not receive clopidogrel in a loading dose, followed by 75 mg/d on top of their OAC for 3 months, and were followed out to a year.

All bleeding that met VARC-2 criteria, the first primary end point, occurred in 21.7% of the 157 patients on OAC alone and 34.6% of the 156 who received double therapy (risk ratio [RR], 0.63; 95% CI, 0.43 - 0.90; P = .011).

The second primary end point, “nonprocedural” bleeding that met BARC-4 criteria, occurred in 21.7% and 34.0%, respectively, of patients (RR, 0.64; 95% CI, 0.44 - 0.92; P = .015).

There were also two secondary composite outcomes. The first consisted of nonprocedural bleeding, cardiovascular (CV) death, any stroke, and MI, and was seen in 31.2% of patients on OAC alone and 45.5% of those on OAC plus clopidogrel (RR, 0.69; 95% CI, 0.51 - 0.92), an absolute difference that was within the prospectively defined noninferiority margins.

The other secondary end point — CV death, ischemic stroke, and MI — occurred in 13.4% of those receiving only OAC and 17.3% on added clopidogrel (RR, 0.77; 95% CI, 0.46 - 1.31), which was nonsignificant for superiority.

“Could they have done better by holding the anticoagulation, whether warfarin or a DOAC, during that time? That’s what I think many centers might do if they’re performing a TAVR,” Bonow said.

“It seems to me that could have been done in this trial as well: they could have stopped the anticoagulation, done the procedure, and started the anticoagulation after, the way you would normally in a patient getting a TAVR.”

Such a practice might have reduced the risk of procedural bleeding as it is usually defined in TAVR in both groups, thereby potentially blunting any difference in bleeding rate between the two groups.

“That’s my take on it.” Still, he said, the trial’s message remains: OAC without clopidogrel is safe in POPULAR-TAVI-like patients.

Nijenhuis had no disclosures. Ten Berg disclosed no industry ties. Disclosures for the other authors are in the report. Bonow has previously reported no disclosures. Dangas has previously disclosed receiving grants and fees from Bayer, fees from Janssen; grants and personal fees from Daiichi-Sankyo; and other compensation from Medtronic. Feit discloses personal fees from Abbott Vascular and other relationships with Medtronic, Boston Scientific, and Sapheon.

This article first appeared on Medscape.com.

A meme has been going around the Internet in which a Muppet is dressed as a doctor, and the caption declares: “If you don’t want to be intubated by a psychiatrist, stay home!” This meme is meant as a commentary on health care worker shortages. But it also touches on the concerns of psychiatrists who might be questioning our role in the pandemic, given that we are physicians who do not regularly rely on labs or imaging to guide treatment. And we rarely even touch our patients.

As observed by Henry A. Nasrallah, MD, editor in chief of Current Psychiatry, who referred to anxiety as endemic during a viral pandemic (Current Psychiatry. 2020 April;19[4]:e3-5), our society is experiencing intense psychological repercussions from the pandemic. These repercussions will evolve from anxiety to despair, and for some, to resilience.

All jokes aside about the medical knowledge of psychiatrists, we are on the cutting edge of how to address the pandemic of fear and uncertainty gripping individuals and society across the nation.

Isn’t it our role as psychiatrists to help people face the reality of personal and societal crises? Aren’t we trained to help people find their internal reserves, bolster them with medications and/or psychotherapy, and prepare them to respond to challenges? I propose that our training and particular experience of hearing patients’ stories has indeed prepared us to receive surreal information and package it into a palatable, even therapeutic, form for our patients.

I’d like to present two cases I’ve recently seen during the first stages of the COVID-19 pandemic juxtaposed with patients I saw during “normal” times. These cases show that, as psychiatrists, we are prepared to face the psychological impact of this crisis.

A patient called me about worsened anxiety after she’d been sidelined at home from her job as a waitress and was currently spending 12 hours a day with her overbearing mother. She had always used her work to buffer her anxiety, as the fast pace of the restaurant kept her from ruminating.

The call reminded me of ones I’d receive from female patients during the MeToo movement and particularly during the Brett Kavanaugh confirmation hearings for the Supreme Court, in which a sexual assault victim and alleged perpetrator faced off on television. During therapy and medication management sessions alike, I would talk to women struggling with the number of news stories about victims coming forward after sexual assault. They were reliving their humiliations, and despite the empowering nature of the movement, they felt vulnerable in the shadow of memories of their perpetrators.

The advice I gave then is similar to the guidance I give now, and also is closely related to the Centers for Disease Control and Prevention advice on its website on how to manage the mental health impact of COVID-19. People can be informed without suffering by taking these steps:

• Limit the amount of news and social media consumed, and if possible, try to schedule news consumption into discrete periods that are not close to bedtime or other periods meant for relaxation.
• Reach out to loved ones and friends who remind you of strength and better times.
• Make time to relax and unwind, either through resting or engaging in an activity you enjoy.
• Take care of your body and mind with exercise.
• Try for 8 hours of sleep a night (even if it doesn’t happen).
• Use techniques such as meditating, doing yoga, or breathing to practice focusing your attention somewhere.

During this crisis, tactful self-disclosure might be appropriate and therapeutic. All of our lives have been disrupted by COVID-19 and acknowledging this to patients can help them feel less isolated and vulnerable. Our patients with diagnosed psychiatric disorders will be more susceptible to crippling anxiety, exacerbations in panic attacks, obsessive-compulsive disorder symptoms, and resurgence of suicidal ideation in the face of uncertainty and despair. They may also be more likely to experience the socioeconomic fallout of this pandemic. But it’s not just these individuals who will be hit with intense feelings as we wonder what the next day, month, or 6 months hold for us, our families, our friends, our country, and our world.

Recently, I had one of the more surreal experiences of my professional life. I work as a consulation-liaison psychiatrist on the medical wards, and I was consulted to treat a young woman from Central America with schizophrenia who made a serious suicide attempt in mid-February before COVID-19 was part of the lexicon.

After an overdose, she developed aspiration pneumonia and acute respiratory distress syndrome and ended up in the ICU on a respirator for 3 weeks. Her doctors and family were certain she would die, but she miraculously survived. By the time she was extubated and less delirious from her medically induced coma, the hospital had restricted all visitors because of COVID-19.

Because I speak Spanish, we developed as decent a working relationship as we could, considering the patient’s delirium and blunted affect. On top of restarting her antipsychotics, I had to inform her that her family was no longer allowed to come visit her. Outside of this room, I vacillated on how to tell a woman with a history of paranoia that the hospital would not allow her family to visit because we were in the middle of a pandemic. A contagious virus had quickly spread around the world, cases were now spiking in the United States, much of the country was on lockdown, and the hospital was limiting visitors because asymptomatic individuals could bring the virus into the hospital or be infected by asymptomatic staff.

As the words came out of my mouth, she looked at me as I have looked at psychotic individuals as they spin me yarns of impossible explanation for their symptoms when I know they’re simply psychotic and living in an alternate reality. Imagine just waking up from a coma and your doctor coming in to tell you: “The U.S. is on lockdown because a deadly virus is spreading throughout our country.” You’d think you’ve woken up in a zombie film. Yet, the patient simply nodded and asked: “Will I be able to use the phone to call my family?” I sighed with relief and helped her dial her brother’s number.

Haven’t we all listened to insane stories while keeping a straight face and then answered with a politely bland question? Just a few months ago, I treated a homeless woman with schizophrenia who calmly explained to me that her large malignant ovarian tumor (which I could see protruding under her gown) was the unborn heir of Queen Victoria and Prince Albert. If she allowed the doctors to take it out (that is, treat her cancer) she’d be assassinated by the Russian intelligence agency. She refused to let the doctors sentence her to death. Ultimately, we allowed her to refuse treatment. Despite a month of treatment with antipsychotic medication, her psychotic beliefs did not change, and we could not imagine forcing her through surgery and chemotherapy. She died in hospice.

I’ve walked the valleys of bizarro land many times. Working through the dark reality of COVID-19 should be no match for us psychiatrists who have listened to dark stories and responded with words of comfort or empathic silence. As mental health clinicians, I believe we are well equipped to fight on the front lines of the pandemic of fear that has arrested our country. We can make ourselves available to our patients, friends, family, and institutions – medical or otherwise – that are grappling with how to cope with the psychological impact of COVID-19.

Dr. Posada is a consultation-liaison psychiatry fellow with the Inova Fairfax Hospital/George Washington University program in Falls Church, Va., and associate producer of the MDedge Psychcast. She changed key details about the patients discussed to protect their confidentiality. Dr. Posada has no conflicts of interest.

A meme has been going around the Internet in which a Muppet is dressed as a doctor, and the caption declares: “If you don’t want to be intubated by a psychiatrist, stay home!” This meme is meant as a commentary on health care worker shortages. But it also touches on the concerns of psychiatrists who might be questioning our role in the pandemic, given that we are physicians who do not regularly rely on labs or imaging to guide treatment. And we rarely even touch our patients.

As observed by Henry A. Nasrallah, MD, editor in chief of Current Psychiatry, who referred to anxiety as endemic during a viral pandemic (Current Psychiatry. 2020 April;19[4]:e3-5), our society is experiencing intense psychological repercussions from the pandemic. These repercussions will evolve from anxiety to despair, and for some, to resilience.

All jokes aside about the medical knowledge of psychiatrists, we are on the cutting edge of how to address the pandemic of fear and uncertainty gripping individuals and society across the nation.

Isn’t it our role as psychiatrists to help people face the reality of personal and societal crises? Aren’t we trained to help people find their internal reserves, bolster them with medications and/or psychotherapy, and prepare them to respond to challenges? I propose that our training and particular experience of hearing patients’ stories has indeed prepared us to receive surreal information and package it into a palatable, even therapeutic, form for our patients.

I’d like to present two cases I’ve recently seen during the first stages of the COVID-19 pandemic juxtaposed with patients I saw during “normal” times. These cases show that, as psychiatrists, we are prepared to face the psychological impact of this crisis.

A patient called me about worsened anxiety after she’d been sidelined at home from her job as a waitress and was currently spending 12 hours a day with her overbearing mother. She had always used her work to buffer her anxiety, as the fast pace of the restaurant kept her from ruminating.

The call reminded me of ones I’d receive from female patients during the MeToo movement and particularly during the Brett Kavanaugh confirmation hearings for the Supreme Court, in which a sexual assault victim and alleged perpetrator faced off on television. During therapy and medication management sessions alike, I would talk to women struggling with the number of news stories about victims coming forward after sexual assault. They were reliving their humiliations, and despite the empowering nature of the movement, they felt vulnerable in the shadow of memories of their perpetrators.

The advice I gave then is similar to the guidance I give now, and also is closely related to the Centers for Disease Control and Prevention advice on its website on how to manage the mental health impact of COVID-19. People can be informed without suffering by taking these steps:

• Limit the amount of news and social media consumed, and if possible, try to schedule news consumption into discrete periods that are not close to bedtime or other periods meant for relaxation.
• Reach out to loved ones and friends who remind you of strength and better times.
• Make time to relax and unwind, either through resting or engaging in an activity you enjoy.
• Take care of your body and mind with exercise.
• Try for 8 hours of sleep a night (even if it doesn’t happen).
• Use techniques such as meditating, doing yoga, or breathing to practice focusing your attention somewhere.

During this crisis, tactful self-disclosure might be appropriate and therapeutic. All of our lives have been disrupted by COVID-19 and acknowledging this to patients can help them feel less isolated and vulnerable. Our patients with diagnosed psychiatric disorders will be more susceptible to crippling anxiety, exacerbations in panic attacks, obsessive-compulsive disorder symptoms, and resurgence of suicidal ideation in the face of uncertainty and despair. They may also be more likely to experience the socioeconomic fallout of this pandemic. But it’s not just these individuals who will be hit with intense feelings as we wonder what the next day, month, or 6 months hold for us, our families, our friends, our country, and our world.

Recently, I had one of the more surreal experiences of my professional life. I work as a consulation-liaison psychiatrist on the medical wards, and I was consulted to treat a young woman from Central America with schizophrenia who made a serious suicide attempt in mid-February before COVID-19 was part of the lexicon.

After an overdose, she developed aspiration pneumonia and acute respiratory distress syndrome and ended up in the ICU on a respirator for 3 weeks. Her doctors and family were certain she would die, but she miraculously survived. By the time she was extubated and less delirious from her medically induced coma, the hospital had restricted all visitors because of COVID-19.

Because I speak Spanish, we developed as decent a working relationship as we could, considering the patient’s delirium and blunted affect. On top of restarting her antipsychotics, I had to inform her that her family was no longer allowed to come visit her. Outside of this room, I vacillated on how to tell a woman with a history of paranoia that the hospital would not allow her family to visit because we were in the middle of a pandemic. A contagious virus had quickly spread around the world, cases were now spiking in the United States, much of the country was on lockdown, and the hospital was limiting visitors because asymptomatic individuals could bring the virus into the hospital or be infected by asymptomatic staff.

As the words came out of my mouth, she looked at me as I have looked at psychotic individuals as they spin me yarns of impossible explanation for their symptoms when I know they’re simply psychotic and living in an alternate reality. Imagine just waking up from a coma and your doctor coming in to tell you: “The U.S. is on lockdown because a deadly virus is spreading throughout our country.” You’d think you’ve woken up in a zombie film. Yet, the patient simply nodded and asked: “Will I be able to use the phone to call my family?” I sighed with relief and helped her dial her brother’s number.

Haven’t we all listened to insane stories while keeping a straight face and then answered with a politely bland question? Just a few months ago, I treated a homeless woman with schizophrenia who calmly explained to me that her large malignant ovarian tumor (which I could see protruding under her gown) was the unborn heir of Queen Victoria and Prince Albert. If she allowed the doctors to take it out (that is, treat her cancer) she’d be assassinated by the Russian intelligence agency. She refused to let the doctors sentence her to death. Ultimately, we allowed her to refuse treatment. Despite a month of treatment with antipsychotic medication, her psychotic beliefs did not change, and we could not imagine forcing her through surgery and chemotherapy. She died in hospice.

I’ve walked the valleys of bizarro land many times. Working through the dark reality of COVID-19 should be no match for us psychiatrists who have listened to dark stories and responded with words of comfort or empathic silence. As mental health clinicians, I believe we are well equipped to fight on the front lines of the pandemic of fear that has arrested our country. We can make ourselves available to our patients, friends, family, and institutions – medical or otherwise – that are grappling with how to cope with the psychological impact of COVID-19.

Dr. Posada is a consultation-liaison psychiatry fellow with the Inova Fairfax Hospital/George Washington University program in Falls Church, Va., and associate producer of the MDedge Psychcast. She changed key details about the patients discussed to protect their confidentiality. Dr. Posada has no conflicts of interest.

A meme has been going around the Internet in which a Muppet is dressed as a doctor, and the caption declares: “If you don’t want to be intubated by a psychiatrist, stay home!” This meme is meant as a commentary on health care worker shortages. But it also touches on the concerns of psychiatrists who might be questioning our role in the pandemic, given that we are physicians who do not regularly rely on labs or imaging to guide treatment. And we rarely even touch our patients.

As observed by Henry A. Nasrallah, MD, editor in chief of Current Psychiatry, who referred to anxiety as endemic during a viral pandemic (Current Psychiatry. 2020 April;19[4]:e3-5), our society is experiencing intense psychological repercussions from the pandemic. These repercussions will evolve from anxiety to despair, and for some, to resilience.

All jokes aside about the medical knowledge of psychiatrists, we are on the cutting edge of how to address the pandemic of fear and uncertainty gripping individuals and society across the nation.

Isn’t it our role as psychiatrists to help people face the reality of personal and societal crises? Aren’t we trained to help people find their internal reserves, bolster them with medications and/or psychotherapy, and prepare them to respond to challenges? I propose that our training and particular experience of hearing patients’ stories has indeed prepared us to receive surreal information and package it into a palatable, even therapeutic, form for our patients.

I’d like to present two cases I’ve recently seen during the first stages of the COVID-19 pandemic juxtaposed with patients I saw during “normal” times. These cases show that, as psychiatrists, we are prepared to face the psychological impact of this crisis.

A patient called me about worsened anxiety after she’d been sidelined at home from her job as a waitress and was currently spending 12 hours a day with her overbearing mother. She had always used her work to buffer her anxiety, as the fast pace of the restaurant kept her from ruminating.

The call reminded me of ones I’d receive from female patients during the MeToo movement and particularly during the Brett Kavanaugh confirmation hearings for the Supreme Court, in which a sexual assault victim and alleged perpetrator faced off on television. During therapy and medication management sessions alike, I would talk to women struggling with the number of news stories about victims coming forward after sexual assault. They were reliving their humiliations, and despite the empowering nature of the movement, they felt vulnerable in the shadow of memories of their perpetrators.

The advice I gave then is similar to the guidance I give now, and also is closely related to the Centers for Disease Control and Prevention advice on its website on how to manage the mental health impact of COVID-19. People can be informed without suffering by taking these steps:

• Limit the amount of news and social media consumed, and if possible, try to schedule news consumption into discrete periods that are not close to bedtime or other periods meant for relaxation.
• Reach out to loved ones and friends who remind you of strength and better times.
• Make time to relax and unwind, either through resting or engaging in an activity you enjoy.
• Take care of your body and mind with exercise.
• Try for 8 hours of sleep a night (even if it doesn’t happen).
• Use techniques such as meditating, doing yoga, or breathing to practice focusing your attention somewhere.

During this crisis, tactful self-disclosure might be appropriate and therapeutic. All of our lives have been disrupted by COVID-19 and acknowledging this to patients can help them feel less isolated and vulnerable. Our patients with diagnosed psychiatric disorders will be more susceptible to crippling anxiety, exacerbations in panic attacks, obsessive-compulsive disorder symptoms, and resurgence of suicidal ideation in the face of uncertainty and despair. They may also be more likely to experience the socioeconomic fallout of this pandemic. But it’s not just these individuals who will be hit with intense feelings as we wonder what the next day, month, or 6 months hold for us, our families, our friends, our country, and our world.

Recently, I had one of the more surreal experiences of my professional life. I work as a consulation-liaison psychiatrist on the medical wards, and I was consulted to treat a young woman from Central America with schizophrenia who made a serious suicide attempt in mid-February before COVID-19 was part of the lexicon.

After an overdose, she developed aspiration pneumonia and acute respiratory distress syndrome and ended up in the ICU on a respirator for 3 weeks. Her doctors and family were certain she would die, but she miraculously survived. By the time she was extubated and less delirious from her medically induced coma, the hospital had restricted all visitors because of COVID-19.

Because I speak Spanish, we developed as decent a working relationship as we could, considering the patient’s delirium and blunted affect. On top of restarting her antipsychotics, I had to inform her that her family was no longer allowed to come visit her. Outside of this room, I vacillated on how to tell a woman with a history of paranoia that the hospital would not allow her family to visit because we were in the middle of a pandemic. A contagious virus had quickly spread around the world, cases were now spiking in the United States, much of the country was on lockdown, and the hospital was limiting visitors because asymptomatic individuals could bring the virus into the hospital or be infected by asymptomatic staff.

As the words came out of my mouth, she looked at me as I have looked at psychotic individuals as they spin me yarns of impossible explanation for their symptoms when I know they’re simply psychotic and living in an alternate reality. Imagine just waking up from a coma and your doctor coming in to tell you: “The U.S. is on lockdown because a deadly virus is spreading throughout our country.” You’d think you’ve woken up in a zombie film. Yet, the patient simply nodded and asked: “Will I be able to use the phone to call my family?” I sighed with relief and helped her dial her brother’s number.

Haven’t we all listened to insane stories while keeping a straight face and then answered with a politely bland question? Just a few months ago, I treated a homeless woman with schizophrenia who calmly explained to me that her large malignant ovarian tumor (which I could see protruding under her gown) was the unborn heir of Queen Victoria and Prince Albert. If she allowed the doctors to take it out (that is, treat her cancer) she’d be assassinated by the Russian intelligence agency. She refused to let the doctors sentence her to death. Ultimately, we allowed her to refuse treatment. Despite a month of treatment with antipsychotic medication, her psychotic beliefs did not change, and we could not imagine forcing her through surgery and chemotherapy. She died in hospice.

I’ve walked the valleys of bizarro land many times. Working through the dark reality of COVID-19 should be no match for us psychiatrists who have listened to dark stories and responded with words of comfort or empathic silence. As mental health clinicians, I believe we are well equipped to fight on the front lines of the pandemic of fear that has arrested our country. We can make ourselves available to our patients, friends, family, and institutions – medical or otherwise – that are grappling with how to cope with the psychological impact of COVID-19.

Dr. Posada is a consultation-liaison psychiatry fellow with the Inova Fairfax Hospital/George Washington University program in Falls Church, Va., and associate producer of the MDedge Psychcast. She changed key details about the patients discussed to protect their confidentiality. Dr. Posada has no conflicts of interest.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Not long ago, weekends for Cornelia Griggs, MD, meant making trips to the grocery store, chasing after two active toddlers, and eating brunch with her husband after a busy work week. But life has changed dramatically for the family since the spread of COVID-19. On a recent weekend, Dr. Griggs and her husband, Robert Goldstone, MD, spent their days off drafting a will.

Courtesy Dr. Cornelia Griggs

“We’re both doctors, and we know that health care workers have an increased risk of contracting COVID,” said Dr. Griggs, a pediatric surgery fellow at Columbia University Irving Medical Center in New York. “It felt like the responsible thing to do: Have a will in place to make sure our wishes are clear about who would manage our property and assets, and who would take care of our kids – God forbid.”

Outlining their final wishes is among many difficult decisions the doctors, both 36, have been forced to make in recent weeks. Dr. Goldstone, a general surgeon at Massachusetts General Hospital in Boston, is no longer returning to New York during his time off, said Dr. Griggs, who has had known COVID-19 exposures. The couple’s children, aged 4 and almost 2, are temporarily living with their grandparents in Connecticut to decrease their exposure risk.

“I felt like it was safer for all of them to be there while I was going back and forth from the hospital,” Dr. Griggs said. “My husband is in Boston. The kids are in Connecticut and I’m in New York. That inherently is hard because our whole family is split up. I don’t know when it will be safe for me to see them again.”

Health professional couples across the country are facing similar challenges as they navigate the risk of contracting COVID-19 at work, while trying to protect their families at home. From childcare dilemmas to quarantine quandaries to end-of-life considerations, partners who work in health care are confronting tough questions as the pandemic continues.

Courtesy Dr. Angela Weyand

Courtesy Dr. Bethany Agusala

Courtesy Dr. Sathya

Editor's Note, 3/31/20: Due to incorrect information provided, the hospital where Dr. Sathya's wife works was misidentified. We have removed the name of that hospital. The story does not include his wife's employer, because Dr. Sathya did not have permission to disclose her workplace and she wishes to remain anonymous.

[email protected]

Not long ago, weekends for Cornelia Griggs, MD, meant making trips to the grocery store, chasing after two active toddlers, and eating brunch with her husband after a busy work week. But life has changed dramatically for the family since the spread of COVID-19. On a recent weekend, Dr. Griggs and her husband, Robert Goldstone, MD, spent their days off drafting a will.

Courtesy Dr. Cornelia Griggs

“We’re both doctors, and we know that health care workers have an increased risk of contracting COVID,” said Dr. Griggs, a pediatric surgery fellow at Columbia University Irving Medical Center in New York. “It felt like the responsible thing to do: Have a will in place to make sure our wishes are clear about who would manage our property and assets, and who would take care of our kids – God forbid.”

Outlining their final wishes is among many difficult decisions the doctors, both 36, have been forced to make in recent weeks. Dr. Goldstone, a general surgeon at Massachusetts General Hospital in Boston, is no longer returning to New York during his time off, said Dr. Griggs, who has had known COVID-19 exposures. The couple’s children, aged 4 and almost 2, are temporarily living with their grandparents in Connecticut to decrease their exposure risk.

“I felt like it was safer for all of them to be there while I was going back and forth from the hospital,” Dr. Griggs said. “My husband is in Boston. The kids are in Connecticut and I’m in New York. That inherently is hard because our whole family is split up. I don’t know when it will be safe for me to see them again.”

Health professional couples across the country are facing similar challenges as they navigate the risk of contracting COVID-19 at work, while trying to protect their families at home. From childcare dilemmas to quarantine quandaries to end-of-life considerations, partners who work in health care are confronting tough questions as the pandemic continues.

Courtesy Dr. Angela Weyand

Courtesy Dr. Bethany Agusala

Courtesy Dr. Sathya

Editor's Note, 3/31/20: Due to incorrect information provided, the hospital where Dr. Sathya's wife works was misidentified. We have removed the name of that hospital. The story does not include his wife's employer, because Dr. Sathya did not have permission to disclose her workplace and she wishes to remain anonymous.

[email protected]

Not long ago, weekends for Cornelia Griggs, MD, meant making trips to the grocery store, chasing after two active toddlers, and eating brunch with her husband after a busy work week. But life has changed dramatically for the family since the spread of COVID-19. On a recent weekend, Dr. Griggs and her husband, Robert Goldstone, MD, spent their days off drafting a will.

Courtesy Dr. Cornelia Griggs

“We’re both doctors, and we know that health care workers have an increased risk of contracting COVID,” said Dr. Griggs, a pediatric surgery fellow at Columbia University Irving Medical Center in New York. “It felt like the responsible thing to do: Have a will in place to make sure our wishes are clear about who would manage our property and assets, and who would take care of our kids – God forbid.”

Outlining their final wishes is among many difficult decisions the doctors, both 36, have been forced to make in recent weeks. Dr. Goldstone, a general surgeon at Massachusetts General Hospital in Boston, is no longer returning to New York during his time off, said Dr. Griggs, who has had known COVID-19 exposures. The couple’s children, aged 4 and almost 2, are temporarily living with their grandparents in Connecticut to decrease their exposure risk.

“I felt like it was safer for all of them to be there while I was going back and forth from the hospital,” Dr. Griggs said. “My husband is in Boston. The kids are in Connecticut and I’m in New York. That inherently is hard because our whole family is split up. I don’t know when it will be safe for me to see them again.”

Health professional couples across the country are facing similar challenges as they navigate the risk of contracting COVID-19 at work, while trying to protect their families at home. From childcare dilemmas to quarantine quandaries to end-of-life considerations, partners who work in health care are confronting tough questions as the pandemic continues.

Courtesy Dr. Angela Weyand

Courtesy Dr. Bethany Agusala

Courtesy Dr. Sathya

Editor's Note, 3/31/20: Due to incorrect information provided, the hospital where Dr. Sathya's wife works was misidentified. We have removed the name of that hospital. The story does not include his wife's employer, because Dr. Sathya did not have permission to disclose her workplace and she wishes to remain anonymous.

[email protected]

AstraZeneca has announced that the phase 3 DAPA-CKD trial for dapagliflozin (Farxiga) in patients with chronic kidney disease has been halted early because of overwhelming efficacy of the drug, at the recommendation of an independent data monitoring committee.

DAPA-CKD is an international, multicenter, randomized, double-blinded trial in 4,245 patients with stage 2-4 chronic kidney disease. Patients received either 10 mg of the dapagliflozin once-daily or a placebo. The primary composite endpoint is worsening of renal function, defined as a composite of an estimated glomerular filtration rate decline of at least 50%, onset of end-stage kidney disease, and death from cardiovascular or renal cause.

The decision to stop the trial came after a routine assessment of efficacy and safety that showed dapagliflozin’s benefits significantly earlier than expected. AstraZeneca will initiate closure of the study, and results will be published and submitted for presentation at a forthcoming medical meeting.

Dapagliflozin is a sodium-glucose transporter 2 inhibitor currently indicated for the treatment type 2 diabetes patients with inadequately controlled type 2 diabetes and for reduction of the risk of hospitalization for heart failure. In August 2019, the drug was granted Fast Track status by the Food and Drug Administration for the treatment of chronic kidney disease. In January 2020, the agency also granted Fast Track status for the reduction of risk of cardiovascular death or worsening of heart failure in adult patients, regardless of diabetes status, with heart failure with reduced ejection fraction.

“Chronic kidney disease patients have limited treatment options, particularly those without type-2 diabetes. We are very pleased the data monitoring committee concluded that patients experienced overwhelming benefit. Farxiga has the potential to change the management of chronic kidney disease for patients around the world,” Mene Pangalos, executive vice president of BioPharmaceuticals R&D, said in the press release.

[email protected]

AstraZeneca has announced that the phase 3 DAPA-CKD trial for dapagliflozin (Farxiga) in patients with chronic kidney disease has been halted early because of overwhelming efficacy of the drug, at the recommendation of an independent data monitoring committee.

DAPA-CKD is an international, multicenter, randomized, double-blinded trial in 4,245 patients with stage 2-4 chronic kidney disease. Patients received either 10 mg of the dapagliflozin once-daily or a placebo. The primary composite endpoint is worsening of renal function, defined as a composite of an estimated glomerular filtration rate decline of at least 50%, onset of end-stage kidney disease, and death from cardiovascular or renal cause.

The decision to stop the trial came after a routine assessment of efficacy and safety that showed dapagliflozin’s benefits significantly earlier than expected. AstraZeneca will initiate closure of the study, and results will be published and submitted for presentation at a forthcoming medical meeting.

Dapagliflozin is a sodium-glucose transporter 2 inhibitor currently indicated for the treatment type 2 diabetes patients with inadequately controlled type 2 diabetes and for reduction of the risk of hospitalization for heart failure. In August 2019, the drug was granted Fast Track status by the Food and Drug Administration for the treatment of chronic kidney disease. In January 2020, the agency also granted Fast Track status for the reduction of risk of cardiovascular death or worsening of heart failure in adult patients, regardless of diabetes status, with heart failure with reduced ejection fraction.

“Chronic kidney disease patients have limited treatment options, particularly those without type-2 diabetes. We are very pleased the data monitoring committee concluded that patients experienced overwhelming benefit. Farxiga has the potential to change the management of chronic kidney disease for patients around the world,” Mene Pangalos, executive vice president of BioPharmaceuticals R&D, said in the press release.

[email protected]

AstraZeneca has announced that the phase 3 DAPA-CKD trial for dapagliflozin (Farxiga) in patients with chronic kidney disease has been halted early because of overwhelming efficacy of the drug, at the recommendation of an independent data monitoring committee.

DAPA-CKD is an international, multicenter, randomized, double-blinded trial in 4,245 patients with stage 2-4 chronic kidney disease. Patients received either 10 mg of the dapagliflozin once-daily or a placebo. The primary composite endpoint is worsening of renal function, defined as a composite of an estimated glomerular filtration rate decline of at least 50%, onset of end-stage kidney disease, and death from cardiovascular or renal cause.

The decision to stop the trial came after a routine assessment of efficacy and safety that showed dapagliflozin’s benefits significantly earlier than expected. AstraZeneca will initiate closure of the study, and results will be published and submitted for presentation at a forthcoming medical meeting.

Dapagliflozin is a sodium-glucose transporter 2 inhibitor currently indicated for the treatment type 2 diabetes patients with inadequately controlled type 2 diabetes and for reduction of the risk of hospitalization for heart failure. In August 2019, the drug was granted Fast Track status by the Food and Drug Administration for the treatment of chronic kidney disease. In January 2020, the agency also granted Fast Track status for the reduction of risk of cardiovascular death or worsening of heart failure in adult patients, regardless of diabetes status, with heart failure with reduced ejection fraction.

“Chronic kidney disease patients have limited treatment options, particularly those without type-2 diabetes. We are very pleased the data monitoring committee concluded that patients experienced overwhelming benefit. Farxiga has the potential to change the management of chronic kidney disease for patients around the world,” Mene Pangalos, executive vice president of BioPharmaceuticals R&D, said in the press release.

[email protected]

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

[email protected]

SOURCE: Boehm M. ACC 2020, Abstract 406-15.