Examining the current state of professionalism and ethics in cardiology.

A Need for Change: Tackling Professionalism and Ethics in Cardiology

While the COVID-19 pandemic has dominated the landscape of healthcare and society in the last year and a half, the ongoing cardiovascular epidemic has not disappeared. Now, possibly more than ever with the crossover between cardiovascular and severe COVID-19 risk factors, the topic of preventive health has begun to take center stage.

Ahead of the American Society for Preventive Cardiology (ASPC) 2021 Virtual Summit, 

reached out to ASPC President-Elect Martha Gulati, MD, to discuss the upcoming conference and hot topics in preventive cardiology. In addition to her role as President-Elect, Gulati is leading a session on ischemic heart disease without obstructive coronary arteries and serving as moderator for a session titled, “The Great Diet Debate”. Set to last from 11:10 AM until 12:10 PM on Saturday, July 24, the 2-hour session featuring Danielle Belardo, MD, Arthur Agatston, MD, Carol Kirkpatrick, PhD, RDN, and Tracy Severson, RD, is among the most anticipated at this year’s meeting.

For more on the topic of nutrition as a pillar of preventive cardiology, ASPC 2021, and cardiovascular medicine, check out our Q&A with Gulati below.

When looking at ASPC this year, the Great Diet Debate stands out. How important is being knowledgeable on the topic of nutrition when it comes to preventive cardiology?

This is a question that comes up clinically for us all the time. Patients are always asking us, 'What should I be eating for heart health?', but sometimes it has to do with weight loss too. Certainly, the two are tied together, but, in general, people want to know what kind of food they should be eating for overall health.

So, clinically it's highly relevant. But, often, our patients they come with the latest diet that they see online, in a book they bought, or that has been talked about on television. So, all of those make us need to know what's truly the evidence behind specific diets and what's just a fad diet or what isn't based on evidence. Despite the fact that you hear people spouting out things about the latest diet fat, a lot of it, I believe, is some of the books that come out. They are just marketing tools and not necessarily based on evidence. We need to tease that out and we need the experts to help us with that—in this particular session, we'll be having one person is presenting on the Mediterranean diet, one person is presenting on plant-based diet, one is presenting on the South Beach diet, and another person is presenting on the keto diet.

What kind of changes are needed to address systemic issues in proper nutrition in the US and elsewhere?

Well, we need to make things that are good for you more accessible and less costly, rather than the bad things that are out there that are cheaper than good food. When you just look simply in a grocery store at what is affordable, how many people can you feed on this, or certain food versus fruits and vegetables, you see there's a big difference in affordability but also the availability to people.

At the moment, we don't grow enough fruits and vegetables in this country. If everyone followed the guidelines and ate the way they were supposed to, we wouldn't have enough fruits and vegetables grown to feed our population. These are things that our policy really needs to address. We can say eat healthily and our government can say eat healthily, but we're not really making it possible for patients. So, there are things that we really need to do as a society to address this. Dairy food, for example, is supplemented by the government and there is a lot of dairy available—and this is not to say that dairy is bad for you, but anything in anything in excess is not good for you. We can probably provide dairy products to the entire United States, but we can't provide vegetables and healthy fruits to all the United States. That's a problem.

That is a problem with our policy and that, ultimately, is going to determine the cost of things that we see on our shelves. I hope that one day we can get to a point you know, I'm a big believer in also trying to teach ourselves to be sustainable. I'm a gardener myself and I often talk to my patients about how they can do gardening and how cheap food can be if you're lucky enough to have some space where you can grow fruits and vegetables. Of course, I'm into the community gardens where people share their foods, grow their foods, and take care of the gardens together.

I think that these are some of the things that we need to try, as a society, to improve it and improve the dietary components that we're bringing to our table every day. But, again, this takes work, takes the right space, and is not available to everyone. We've got to think and be creative about this.

Aside from The Great Diet Debate, what are one or two other sessions at ASPC 2021 you would like to highlight?

One of the sessions I'm very excited about is related to our strategies of care and a lot has changed in healthcare in the last year due to COVID-19. I think telehealth has been an area that has transformed medicine and preventive cardiology. I'm very excited to be listening to Dr. Amy Bhatt's talk on telehealth because I really think this is something that is not going to go away. COVID-19, hopefully, will go away, but telehealth is here to stay; however, we need to refine it for our clinical practices.

Then, the talk that follows is Dr. Seth Martin's talk on technologies and wearables, which is tied in my mind to telehealth—meaning, we can use some of these technologies when patients are at home and we're not seeing them in ways that we never had before. Even if it's just simply checking blood pressure at home, maybe they don't need to come in for that. But even with other technologies and those on our phones, we need to know which ones we can reliably use and the wearables that we can reliably use that can help us measure overall health for our patients. So, I think that's one session.

There is a lot of great sessions on other topics, that I think that prevention usually doesn't cover. For example, we have a session focusing on the health transgender patients. We're seeing more and more of these patients and the effects of hormone replacement on cardiovascular disease is still an area that we don't know as much about, and we need to. I think that this is a great conversation and Dr. Chrisandra Shufelt is one of the leaders in that area. So, we're very excited to have her speaking on that.

Another group we don't talk too much about is patients with physical disabilities and their issues with accessibility, diet, and risk assessment—how do we advise them? I think we really need to know more about that group as well. Our theme this year is protecting the heart of one and all we tried to really bring in some of the areas that we don't always focus on when we talk about prevention.

What do you think is the most exciting area in cardiology right now and why?

 It's so hard to choose just one thing that is exciting. There's so much transforming in cardiology right now, but I'd probably say the one thing that's really exciting is related to diabetes and SGLT2 inhibitors. These were medications that were intended to control diabetes, we're finding may be preventive therapies in heart disease, specifically related to heart failure, and I think that this is really transforming not just the care of patients, but also the practice of cardiologists.

In the past, nobody really wanted to tread on diabetes control in the cardiology community; we felt that was really something that the endocrinologist did or the family physician or the internist did, but not us. Suddenly, we have this amazing medication that we, now, also need to be able to know how to initiate and I think this is really transforming care. Maybe, in a few years, we'll be talking about how we hesitated, but now it's our drug.

I think nephrologists are having the same discussion because these medications appear to also be beneficial for patients who have chronic kidney disease in reducing the advancement of kidney disease. So, I think these drugs are really game-changers.

Something else really exciting on the horizon is obesity and the medications that we have for that. We have a medication that just received FDA approval—semaglutide. I'm really excited by it because we haven't been able to offer a lot to patients to help them lose weight, in terms of medications. I really think this medication can be a game-changer for our patients. Losing weight is probably the most challenging thing for patients, probably just as difficult as when we ask patients to stop smoking and, even with smoking cessation, we actually have some medications there. So, this is a really exciting time to help our patients with cardiovascular disease prevention and with these new therapies.

Editor's note: This transcript has been edited for space and clarity. 

Articles

Martha Gulati, MD, discusses nutrition and its role in preventive cardiology as well as other highlights from the American Society for Preventive Cardiology's 2021 Virtual Summit. 

Nutrition as a Pillar of Preventive Cardiology and Other Highlights from ASPC 2021, with Martha Gulati, MD

Patrick Campbell is the senior editor of Practical Cardiology, as well as its sister publication Endocrinology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

New research from a study of Medicare beneficiaries is underlining the importance of early increases in physical activity, whether through structured rehabilitation or at-home programs, among patients who recently received an implantable cardioverter-defibrillator (ICD).

An analysis of more than 42,000 patients who had ICDs implanted from 2014-2016, results suggest every 10 minutes in daily physical activity was associated with a 1.1% reduction in all-cause mortality and a 1.0% reduction in risk of heart failure hospitalization at 1-year.

“This finding helps confirm prior research showing that cardiac rehabilitation is underutilized, and the benefits of increased physical activity obtained in cardiac rehabilitation programs also may be achievable at home, potentially offering another opportunity to improve outcomes in patients with ICDs,” said study author Brett D. Atwater, MD, director of electrophysiology and electrophysiology research at Inova Heart and Vascular Institute, in a 

press release from the American Heart Association

Despite specific inclusion in major guidelines, cardiac rehabilitation is underutilized, not just in patients with ICDs, but across a spectrum of cardiovascular conditions. With an interest in adding to the growing evidence base supporting use and to push for increased access to these programs, Atwater and colleagues from the Duke University School of Medicine sought to assess the association between physical activity and participation in cardiac rehabilitation programs with risk of death or heart failure hospitalization following ICD implantation.

Investigators designed their study as a retrospective observational study of Medicare beneficiaries who underwent ICD implantation from January 1, 2014, to December 31, 2016. Using Medicare claims data accessed through the Centers for Medicare and Medicaid Services Virtual Research Data Center, investigators identified 41,631 patients who underwent ICD implantation during the period of interest. 

Of note, all patients included in the study had a history of heart failure and coronary artery disease. Patients were excluded if they were enrolled in Medicare for fewer than 12 months prior to index date, if they participated in their first rehabilitation sessions less than 30 days or more than 365 days after implantation.

For the purpose of analysis, participation in cardiac rehabilitation was deranged as having at least one Medicare carrier claim or outpatient claim occurring between 30 and 365 days after ICD implantation. The primary outcome of interest was all-cause mortality and the secondary outcome of interest was hospitalizations for heart failure.

The study cohort had a mean age of 75 (SD, 10) years, 72.3% were male, and the mean baseline physical activity level was 128.9 (SD, 78.4) minutes per day. At 3 years of follow-up, 25.1% of patients in the study cohort had died and 51.7% experienced a heart failure-related hospitalization. Of the 41,731 patients included in the study, only 1324 (3.2%) met the criteria for being considered cardiac rehabilitation participants. Compared to nonparticipants, participants were more likely to be white (91.0% vs 87.3%), male (75.5% vs 72.2%), and more likely to have diabetes (48.8% vs 44.1%), ischemic heart disease (91.4% vs 82.1%), and congestive heart failure (90.4% vs 83.4%).

Among those who participated in cardiac rehabilitation, the median number of sessions was 24 (955 CI, 2-36). Data indicated daily mean physical activity levels increased by 9.7 (SD, 57.8) minutes per day. In contrast, physical activity levels decreased by a mean of 1.0 (SD, 59.7) minutes per day among nonparticipants (

In adjusted analysis, cardiac rehabilitation participants had a 24% lower risk of 1- to 3-year mortality compared to nonparticipants. Further analysis accounting for ICD measured change in physical activity, no differences were observed in mortality with or without cardiac rehabilitation.

Further analysis suggested every 10 minutes of increased daily physical activity during the study period was associated with a 1.1% reduction ion in risk of death at 1-year (HR, 0.989; 95% CI, 0.979-0.996; 

 <.001). A similar trend was seen for risk of heart failure hospitalization, with every 10-minute increase in daily physical activity associated with a 1% reduction in risk (HR, 0.99; 95% CI, 0.986-0.995; 

“Our study examined whether physical activity outside of a formal cardiac rehabilitation program could yield similar benefits, and we found it did,” said Atwater. “This suggests that additional options like home-based cardiac rehabilitation might help more patients realize the health benefits of increased physical activity.”

Early Increased Physical Activity, Cardiac Rehabilitation, and Survival After Implantable Cardioverter-Defibrillator Implantation

Circulation: Cardiovascular Quality and Outcomes.

Analysis of more than 40k Medicare beneficiaries suggests increased physical activity, whether it occurs as part of a rehabilitation or not, was associated with decreased risk of all-cause mortality and hospitalizations for heart failure in patients who recently received an implantable cardioverter-defibrillator. 

With Implantable Cardioverter-Defibrillators, Every 10-Minute Increase in Physical Activity Reduces Mortality Risk by 1.1% 

Over the last 6 months, I have had two patients with more than a heart and lungs in their chest. The first was a retired teacher who developed dyspnea mowing his lawn. It sounded cardiac to me, but his echocardiogram and exercise stress test were normal. I ordered a chest x-ray because, years ago, I had a patient with similar symptoms who turned out to have a paralyzed right hemidiaphragm. 

I was embarrassed by missing that prior patient and, consequently, very proud of myself when the present patient’s chest x-ray showed an elevated right hemidiaphragm. I shipped the patient off to a pulmonologist, who did a radiographic cine sniff test that showed normally moving hemidiaphragms bilaterally, but a very large hiatal hernia. The patient is scheduled for closed hiatal hernia repair because the pulmonologist is convinced that this is the cause of the patient’s dyspnea.

I also recently saw a distance runner with palpitations. He had had palpitations (and gastro-esophageal reflux) for several years but a recent prolonged episode of palpitations sent him to the emergency department (ED). I ordered an event monitor that showed that 10% of his beats were PVCs. His echocardiogram and left ventricular function were normal, but his chest x-ray from the ED showed a large hiatal hernia. Large hiatal hernias have been associated with ventricular ectopy, which was cured by hernia repair.

 We did not pursue hernia repair in this patient because his left ventricular ejection fraction was normal, and he and his wife declined because the patient had early dementia.

So, what’s the point? Consider doing a chest x-ray when patients have dyspnea or frequent palpitations, but no history of lung disease, and a normal cardiac workup. Sometimes there is more in the chest than just a heart and lungs, like a paralyzed hemidiaphragm or most of their stomach.

Posterior cardiac compression from a large hiatal hernia-A novel cause of ventricular tachycardia.

HeartRhythm Case Rep. 2018 May 23;4(8):362-366.

In his most recent column, Dr. Paul Thompson offers perspective on why he feels clinicians should consider performing a chest x-ray in patients with dyspnea or frequent palpitations, but no history of lung disease and a normal cardiac work-up. 

More Than A Heart and Lungs in The Chest, with Paul Thompson, MD

This article was originally published on 

The US Food and Drug Administration (FDA) issued a letter to biopharmaceutical company Ardelyx, Inc, identifying deficiencies in the company’s New Drug Application (NDA) for investigative drug tenapanor ahead of its PDUFA date next week, according to Ardelyx. 

The letter, received on July 13, stated the deficiencies of the NDA “preclude discussion” around the would-be labeling and post-marketing requirements for tenapanor as a drug for controlling serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis.

The FDA noted key issues in the NDA for tenapanor include size and clinical relevance of the treatment effect.

Though the letter stated the notification did not reflect a final decision on the NDA, a meeting requested by the company on the matters of the letter was denied by the FDA.

 accompanying the news, Ardelyx president and chief executive officer Mike Raab expressed disappointment with the communication.

"This is an extremely disheartening and disappointing communication from the FDA, particularly following the weeks of label discussions that occurred in early April, the fact that our NDA submission included three pivotal trials across 1,000 patients, all which met their primary and key secondary endpoints, as well as the additional data analyses we submitted in late April in response to the FDA's requests," Raab said.

He stressed the company plans to work with FDA going forward to interpret the highlighted NDA deficiencies “and will seek to resolve them as quickly as possible.”

 50 mg, twice-daily oral tenapanor to increase bowel movements and decrease abdominal pain for patients with IBS-C.

Citing deficiencies within the New Drug Application submitted for tenapanor for use in patients with chronic kidney disease, the US FDA issued a letter to Ardelyx noting these deficiencies “preclude discussion” related to labeling and post-marketing requirements.

Tenapanor Nixed By FDA, Citing Deficiencies in Application

A look at the association between coffee consumption and risk of cardiac arrhythmia in a patient population of more than 375,000 has returned positive results for habitual coffee drinkers.

Using data from the UK Biobank cohort, a team from the University of California, San Francisco (UCSF) found no evidence moderate coffee consumption was linked to increased risk of arrhythmia and even uncovered evidence suggesting each additional cup of coffee was associated with a 3% lower risk of 

, including atrial fibrillation and supraventricular tachycardia.

"Coffee is the primary source of caffeine for most people, and it has a reputation for causing or exacerbating arrhythmias," said senior and corresponding author Gregory Marcus, MD, professor of medicine in the Division of Cardiology at UCSF, in a 

. "But we found no evidence that caffeine consumption leads to a greater risk of arrhythmias. Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted."

Despite a heightened focus and long-standing interest, the debate around habitual coffee intake and cardiovascular health is one that continues to this day. With this in mind, Marcus and colleagues from UCSF designed the current study with the intent of providing further clarity on the issue. To do so, investigators designed their study as a retrospective analysis of patients from within the UK Biobank cohort.

The overall UK Biobank cohort had a median coffee intake per day of 2 cups (IQR, 1-4). Of the 502,543 participants within the cohort, 386,258 met criteria and were included in statistical analyses. Of these, 310,061 reported consumption of caffeinated coffee, 74,371 reported consuming noncaffeinated coffee, and 83,228 reported not drinking coffee. Compared to their counterparts consuming less than the daily median amount of coffee, those with increased intake e daily median amount of coffee were more likely to be older, White, male, have peripheral artery disease, have cancer, be a current smoker, or drink alcohol and less likely to have hypertension, diabetes, chronic kidney disease, and to drink tea.

Outcomes of interest for the analyses was the incidence of any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. Exposures used in analyses included caffeine intake and a group of genetic polymorphisms that impact caffeine metabolism.

Over a mean follow-up of 4.5 (SD, 3.1) years, 16,979 participants developed an incident arrhythmia. In analyses adjusted for demographic characteristics, comorbidities, and lifestyle factors, results suggested consumption of each additional cup of coffee was associated with a 3% (HR, 0.97; 95% CI, 0.96-0.98; 

 <.001) reduction in his of incident arrhythmia. Additionally, analyses assessing individuals forms of arrhythmia indicated statistically significant associations were observed for atrial fibrillation or flutter (HR, 0.97; 95% CI, 0.96-0.98; 

 <.001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; 

Investigators also pointed out interaction analyses, including one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and other restricted to CYP1A2 rs762551 alone, failed to produce evidence of effect modification. In a Mendelian randomization study using these same genetic variants, results suggested no significant association existed between underlying propensities to differing metabolism and risk of incident arrhythmia.

In the aforementioned press release, Marcus acknowledged the inherent limitations of their study due to the nature of its design.

“Only a randomized clinical trial can definitively demonstrate clear effects of coffee or caffeine consumption," said Marcus. "But our study found no evidence that consuming caffeinated beverages increased the risk of arrhythmia. Coffee's antioxidant and anti-inflammatory properties may play a role, and some properties of caffeine could be protective against some arrhythmias."

Coffee Consumption and Incident Tachyarrhythmias—Reported Behavior, Mendelian Randomization, and Their Interactions

Analysis of data from the UK Biobank cohort suggests consumption of coffee was not linked to an increased risk of arrhythmias, with some evidence indicating habitual use was linked to a decrease in incidence of atrial fibrillation or flutter and supraventricular tachycardia. 

No Evidence Coffee Consumption Increases Risk of Arrhythmias, UCSF Study Finds

Results of an open-label, parallel-group trial suggest use of abelacimab, a novel, fully human, Factor XI and XIa antibody, was associated with a reduction in risk of blood clots following surgery without increasing the risk of bleeding compared to current standard of care.

A comparison of abelacimab to enoxaparin in a cohort of 412 patients undergoing orthopedic surgery, results of the trial not only demonstrate the ability of abelacimab to aid in prevention of blood clots but also outline the role of factor XI in clot formation following surgery.

"This success of abelacimab in this study provides the foundation for its use for prevention of stroke in patients with atrial fibrillation and for treatment of deep-vein thrombosis and pulmonary embolism, clots in the veins of the leg and clots in the lung, in patients with cancer," said Jeffrey Weitz, MD, senior investigator of the trial who also serves as the professor of medicine and of biochemistry and biomedical sciences at McMaster's Michael G. DeGroote School of Medicine and executive director of the Thrombosis and Atherosclerosis Research Institute, 

Named ANT-005 and funded by Anthos Therapeutics, the multicenter, randomized, open-label trial was designed to compare intravenous abelacimab in 30 mg, 75, mg, or 150 mg doses against enoxaparin 40 mg. Conducted at 16 centers in 5 countries, the trial enrolled a population of 412 patients undergoing total knee arthroplasty. The trial’s primary efficacy outcome of interest was the incidence of venous thromboembolism and the primary safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.

For the primary efficacy outcome, which was assessed via a mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events, results indicated venous thromboembolism occurred among 13 of 102 (13%) patients in the 30 mg abelacimab group, 5 of 99 (5%) patients in the 75 mg group, and 4 of 98 (4%) patients in the 150 mg group, and 22 of 101 (22%) patients in the enoxaparin group.

Results of the investigators’ analyses indicated the 30 mg dose of abelacimab was noninferior to enoxaparin and the 75 mg and 150 mg doses of abelacimab were considered superior to enoxaparin (

 <.001). Additionally, the difference in risk seen with abelacimab compared to enoxaparin was -9.2 percentage point for 30 mg abelacimab (95% CI, -19.4 to 1.1; 

=.08 for superiority), -16.8 percentage points for 75 mg abelacimab (95% CI, -26.0 to -7.6; 

 <.001 for superiority), and -17.8 percentage points with 150 mg abelacimab (95% CI, -26.7 to -8.8; 

In safety analyses, bleeding events were observed in 2% of patients receiving 30 mg abelacimab, 2% receiving 75 mg abelacimab, and 0 patients receiving 150 mg abelacimab. No bleeding events were observed among patients in the enoxaparin group.

In the aforementioned statement, Weitz outlined the potential impact of using factor XI as a target for anticoagulation strategies.

"We expect factor XI to be a safer target for new anticoagulants than the targets of currently available anticoagulants because patients with congenital factor XI deficiency are at reduced risk for clots but rarely have spontaneous bleeding," Weitz added.

Abelacimab for Prevention of Venous Thromboembolism

New England Journal of Medicine and presented at the 

International Society on Thrombosis and Hemostasis 2021 Congress.

A 412-patient trial comparing 3 dosing regimens of abelacimab versus enoxaparin, results indicate all 3 regimens of abelacimab demonstrated noninferiority against enoxaparin and 2 of the 3 demonstrated superiority against the current standard of care. 

Abelacimab Demonstrates Potential of Factor XI Inhibition in Preventing Blood Clots

AstraZeneca and FibroGen received a disheartening blow on July 15, when the US Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against recommending approval of roxadustat for the treatment of anemia in adult patients with chronic kidney disease (CKD).

The committee voted 13-1 against the approval for treatment of chronic kidney disease in patients not on dialysis (NDD) and 12-2 against the approval for patients on dialysis (DD), citing concerns over an increased risk for thrombotic events and other major cardiovascular adverse events.

“New solutions are needed for the six million people in the US affected by anemia of chronic kidney disease. Although we are disappointed by today’s outcome, we will continue to work closely with our partner FibroGen and the FDA to determine the path forward for roxadustat,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, in a 

, who is developing the agent in collaboration with FibroGen Inc and Astellas Pharma Inc.

“While we are disappointed with today's outcome,” said Enrique Conterno, Chief Executive Officer of FibroGen,

. “We believe the scientific evidence supports roxadustat approval in the U.S. and will work with the FDA as it completes its review of the New Drug Application for roxadustat.”

An oral, small molecule, hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, roxadustat was the first HIF-PH inhibitor to be accepted by the FDA for review in treatment of anemia in patients with CKD. Evaluated in a phase 3 program including more than 8000 patients and half a dozen trials, data behind roxadustat has warranted approval in other countries such as China, Japan, Chile, and South Korea for treatment of anemia in CKD in NDD and DD patients. The agent is also under final regulatory review with the European Medicines Agency.

“The sponsor has done its clinical trials with a very specific strategy but now would like approval for a strategy which has been developed only as a simulation. If they really want people to use the new strategy in clinical practice, they really do need to test it and show its efficacy and safety,” said Milton Packer, MD, FDA CRDAC committee member and cardiologist at Baylor Medical Center, after voting against recommending approval for treatment of anemia due to CKD in NDD.

The FDA's CRDAC July 15 meeting concluded with committee members voting against recommending the approval of roxadustat for the treatment of anemia in adult patients with chronic kidney disease not on dialysis and on dialysis.

Roxadustat Receives Negative Vote from FDA Panel Ahead of PDUFA Date


A new scientific statement from the American Heart Association is outlining the importance and possible avenues for improving involvement of primary care for care of adult patients after 

The statement, “Primary Care of Adult Patients After Stroke,” was released by the American Heart Association (AHA) and the American Stroke Association (ASA).

The statement highlighted the need for comprehensive post-stroke management, including engaged caregivers and family members in supporting the patient.

In addition, it stressed the need for an earlier post-stroke primary care appointment, which may reduce hospital admission and address gaps in care that may lead to high risk of stroke recurrence.

The complexities of stroke were also highlighted, citing approximately 800,000 adults in the US will have a new stroke each year, while 10% will die within 30 days.

Further, data show by 90 days after stroke, new-stroke related disability developed in 10% of younger adults to 30% in adults aged >65 years.

The statement noted screenings should assess new or chronic risk of recurrent stroke, including high blood pressure, high cholesterol, diabetes, atrial fibrillation and blockage in carotid artery, as well as complications including anxiety, depression, and cognitive impairment.

Walter N. Kernan, MD, chair of the statement writing group, professor of medicine at Yale University School of Medicine, said the new statement affirmed the new role of the primary care professional in the care of people with stroke.

“Primary care professionals can ensure consistent and comprehensive care for the full needs of patients, including coordinating any additional care or services patients may need from community services providers or from subspecialty health care providers,” Kernan said.

Data show the risk of recurrent stroke will reach 8% in the first year following an ischemic stroke, while the annual risk after the first year is 2%, nearly 4 times higher risk than a person without prior stroke.

The guidelines mentioned that while most patients will have a stroke due to cardioembolism, large-vessel disease, or small-vessel disease, it may be important to consider other causes including arterial dissection, vasculitis, or sickle cell disease.

The statement indicated the first step in outpatient primary care is to confirm the cause of stroke, while diagnostic tests that have not been completed should be prioritized, including carotid imaging and cardiac rhythm monitoring.

The cause of stroke remains uncertain for 30% of patients, Kernan and colleagues noted.

The statement included the class 1 treatment recommendations from the AHA/ASA.

Proven treatments in the prevention of recurrent vascular events included carotid revascularization for carotid stenosis, anticoagulation for atrial fibrillation, BP lowering, statin therapy, and anti-platelet therapy.

Further, lifestyle improvements, diabetes management, and weight optimization are recommended as Class 1 due to evidence of reduction of risk factors for stroke, rather than prevention of recurrent stroke.

The importance of hypertension management was observed, citing 2 trials that showed blood pressure lowering following stroke reduced the risk for stroke recurrence by 30%.

They provided guidance on diagnostic evaluation, including imaging of the carotid artery for anterior circular stroke events and ECG to screen for atrial fibrillation (AF). 

Next, they discussed vascular risk factor management to recommend and facilitate optimal lifestyle practices, as well as treat hypertension to a goal of <130/80 mm Hg. 

The statement included additional recommendations for management of large-artery atherosclerosis, such as prescribing 325 mg/d aspirin for patients with stroke related to 50% - 99% intracranial stenosis. 

In addition, guidance on cardioembolism included prescribing an oral anticoagulation for AF or flutter unless contraindicated and recommended warfarin over novel oral anticoagulants. 

Further, patient behavior guidelines included behavior change to improve stroke literacy, lifestyle, and medication adherence. 

Another guideline included health equity to address social determinants of health, including literacy level, language proficiency, medication affordability, food insecurity, housing, transportation, in managing stroke risk factors. 

Lastly, guidelines included antithrombotic medications, recommending non-cardioembolic ischemic stroke or TIA, aspirin 50–325 mg, clopidogrel 75 mg, or combination aspirin 25 mg/dipyridamole 200 mg twice daily.  

In a commentary accompanying the statement, Deborah A. Levine MD, MPH, of the Department of Neurology and Stroke Program at University of Michigan, noted the lethality of recurrent stroke.

“Recurrent strokes are more lethal, disabling, and costly than first strokes,” Levine said. “While up to 80% of recurrent strokes are preventable, many individuals with stroke have uncontrolled, modifiable risk factors, increasing their risk for recurrent stroke.”

She noted the risk factors of hypertension and tobacco smoking are increasing in Americans with stroke.

Patients with stroke are also associated with accelerated cognitive decline, with Levine noting the guidelines were justified in recommending cognitive impairment screening to reveal “cognitive deficits.”

Levine also observed the need for improvement in access to high-quality care provided in the statement for all individuals at risk of stroke.

“Still, we need policy and health system-level interventions to ensure that all individuals with stroke get high-quality care and reduce the burden on individual primary care providers,” Levine said. “Like other individuals with disabilities, individuals with stroke frequently have problems accessing and getting high-quality health care.”

The full-text of the AHA statement is available 

The American Heart Association and American Stroke Association recognize the important role of primary care in patient management following a stroke.

American Heart Association Highlights Role of Primary Care in Stroke Recovery

Data from a 10-year study including more than 800 men suggests testosterone therapy could reduce risk of major adverse cardiovascular events (MACE) among men with testosterone deficiency.

Presented at the Annual Congress of the European Association of Urology (EAU21), results of the study indicate men with testosterone deficiency receiving testosterone therapy had a lower risk of mortality and MACE than their counterparts who did not undergo testosterone therapy.

"Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5 to 10 years, with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It's clear that this treatment can significantly reduce the risks in this particular group,” said study presenter Omar Aboumarzouk, PhD, of the Hamad Medical Corporation in Qatar, 

A cumulative registry study designed to assess the long-term safety and efficacy of testosterone therapy in hypogonadal men, the EAU21 study included 805 participants, including 412 receiving 1000 mg of parenteral testosterone every 12 weeks for up to 12 years and 393 who opted against receiving testosterone therapy who served as controls. All patients included in the study were at increased risk of cardiovascular disease due to family history, blood pressure, lipid profile, diabetes status, or body weight.

Upon analysis, results indicated those in the testosterone therapy group had a 10-year mean risk of 22.7% compared to 23.5% among those in the control arm (

=.11). Over a median follow-up of 8 years, 16 deaths occurred in the testosterone therapy group. Investigators pointed out there were no observed incidences of myocardial infarction or stroke among these patients. Over a median follow-up time of 9 years, a total of 74 deaths occurred among those in the control arm. Investigators pointed out 70 incidences of myocardial infarction and 59 cases of stroke were observed among these patients.

Additionally, further analysis suggested use of testosterone therapy was associated with improvements in multiple classical cardiovascular risk factors, including obesity, glycemic control, lipid profile, and CRP.

In the aforementioned statement, Maarten Albersen, Member of the EAU Scientific Office, from Leuven University in Belgium, commended study authors for their study’s addition to the existing knowledge base but cautioned more research into the effects of testosterone on cardiovascular health is needed before drawing a definitive conclusion.

“These were men with a medium risk of heart attack or stroke, and those receiving testosterone were younger and had a slightly lower risk at the start of the study. The study was long enough to see differences in the rate of cardiovascular events,” pointed out Albersen. “However, the numbers involved and the fact that the trial was not randomised mean it's still difficult to draw any hard conclusions. A new trial is now underway, aiming to recruit 6000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone."

This study, “Less mortality and less Major Adverse Cardiovascular Events (MACE) under long-term Testosterone Therapy (TTh): 15-year data from a prospective controlled registry study,” was presented at the Annual Congress of the European Association of Urology.

A 10-year study presented at the European Association of Urology meeting indicates testosterone therapy was associated with a decreased risk of major adverse cardiovascular events in men with hypogonadism. 

Testosterone Therapy Linked to Reduced MACE Risk in Men with Hypogonadism

New research from a team based out of San Jose, CA is providing detail into the impact methamphetamine-associated 

 has had in California for more than a decade.

A look at statewide heart failure data from 2008-2018, results demonstrate a more than 500% increase in the incidence of methamphetamine-associated heart failure and provide insight into the 840% jump in hospitalization costs associated with these events —from $41.5 million in 2008 to $390.2 million in 2018.

"Our study results should bring urgent attention to this insidious yet rapidly growing form of severe heart failure - methamphetamine-related heart failure, which is taking the lives of young people, straining health care resources and threatening to spread like wildfire in California, the West and to the rest of the nation," said lead author Susan X. Zhao, MD, Cardiologist at Santa Clara Valley Medical Center in San Jose, California, 

. "California is seeing a resurgence of methamphetamine use, and the problem has been made drastically worse in recent years by the increase in purer, more potent methamphetamine throughout our communities."

As use of methamphetamine ballooned in the past decade and a half in California, reports suggest the incidence of methamphetamine-associated heart failure hospitalizations has increased as well, but little data has been produced beyond observational reports on the subject. To provide a greater evidence base related to the increased prevalence of methamphetamine-associated heart failure, Zhao and colleagues from northern California-based institutions designed their study to examine trends from data provided by the State of California Health and Human Services Agency’s Office of Statewide Health Planning and Development (OSHPD).

The primary outcomes of interest for the investigators’ analyses included age-adjusted hospitalization rates per 100,000 adults, crude hospitalization rate based on race/sex subgroups, inflation-adjusted annual heart failure hospitalization charges, and temporal or geospatial patterns in distribution of methamphetamine-related heart failure hospitalizations. Investigators pointed out the use of OSHPD data allowed for adjustment for confounders including county, zip code or residence, race/ethnicity, hospital county/zip codes, adjusted length of stay, primary and other procedures performed, and source of payment.

From 2008-2018, investigators identified 4,808,506 adults heart failure hospitalizations. Of these, 1,033,076 hospitalizations had heart failure listed as the primary diagnosis, including 42,565 considered methamphetamine-associated heart failure.

The rate of age-adjusted methamphetamine-associated heart failure hospitalizations increased from 4.1 per 100,000 in 2008 to 28.1 per 100,000 in 2018, which is reflective of a 585% increase. In contrast, the rate of non-methamphetamine-associated heart failure hospitalizations was 342.3 per 100,000 in 2008 and decreased by 6.0% to 321.6 in 2018. Investigators pointed out the rate of increase seen with methamphetamine-associated heart failure hospitalizations was more than double that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold vs 3.48-fold, 

When assessing the financial impact, results indicated the annual inflation-adjusted hospitalization charges as a result of methamphetamine-associated heart failure hospitalizations increased by 840% from $41.5 million in 2008 to $390.2 million in 2018. In comparison, the charges attributable to all heart failure hospitalizations increased just 82% from $3.503 billion in 2008 to $6.376 billion in 2018.

Further analysis indicated patients with methamphetamine-associated heart failure were significantly younger, more likely to be male, and have a lower Charlson Comorbidity Index than those with non-methamphetamine-associated heart failure. Additionally, those with methamphetamine-associated heart failure had longer length of stay, more hospitalizations per patient, and greater number of procedures performed during their stays. 

, Pavan Reddy, MD, and Uri Elkayam, MD, commend Zhao and colleagues for their study’s addition to the existing knowledge base, but also note the need for greater research and interventions to mitigate the impact of methamphetamine-associated heart failure hospitalizations.

“The rising prevalence of MethHF should ring alarm bells but also signals an opportunity. Until recently, MethHF was highlighted only in the form of isolated case reports but is now seen regularly in high usage areas. Although this study makes strides in underscoring the potential societal impact of this protracted illness, prospective data from larger cohorts may help clarify questions left unanswered by the current study,” wrote Reddy and Elkayam.

Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018

From 2008 to 2018, the rate of methamphetamine-associated heart failure hospitalizations in California has risen by nearly 600% while the costs associated with these events has risen by more than 800% during that same time frame. 

Methamphetamine-Associated Heart Failure Placing Major Burden on California Health Care Systems

New research from a pair of studies suggests use of hearts from illicit drug users or overdosed patients is not only safe for transplant but could also cut wait time for recipients.

While some have shied away from use of donor heart from patients who overdosed or used illicit drugs in the past, results of one study demonstrate history nor toxicological evidence of drug use was associated in significant differences in survival among recipients and the other details improvements in survival in recent years among transplant recipients despite increases in donor hearts from patients with comorbidities and other risk factors.

“We thought that illicit drugs like cocaine or methamphetamine, which can lead to heart attacks, would prove to be dangerous,” said David Baran, MD, System Director for Advanced Heart Failure and transplantation at Sentara Heart Hospital in Virginia, who led the study examining hearts of intoxicated donors and transplant outcomes, in a 

. “However, we were wrong. We should not reject a heart from a donor just because they used one or more illicit drugs.”

A byproduct of the opioid crisis in the US has been a surge in the availability of donor hearts from individuals with historic or toxicological evidence of drug use. Despite some previous studies suggesting these hearts were safe for transplant, some institutions still refrain from using these hearts for transplantation, even if it means longer wait times for recipients. This paradox is what spurred Baran and colleagues to design their study examining the long-term outcomes in recipients of hearts from intoxicated donors compared to those from patients without a history of illicit drug use.

 Using the United Network for Organ Sharing (UNOS) database, investigators identified 23,478 adult heart transplants occurring between 2007-2017. In Cox proportional hazards models, results indicated there were no statistically significant differences in post-transplant mortality based on toxicological and historic data. Investigators noted this was despite the number and percent of donors with drug use significantly increasing during the study period (

Further analysis indicated combinations of drugs identified by toxicology were not associated with significant differences in survival following transplant. Investigators also pointed out lower donor age and ischemic time were significantly positively associated with survival (

The second study, which was led by Ravi Dhingra, MD, MPH, Medical Director of the Heart Failure and Transplant Program and Associate Professor of Medicine at the University of Wisconsin-Madison, sought to examine how recent trends may have impacted the donor to transplant ratio or transplant outcomes.

In this study, investigators compared donors and recipients from 2008-2012 (n=11,654) and from 2013-2017 (n=14,556) to counterparts from 2003-2007 (n=10,869) using information obtained from the UNOS. Using Cox models, investigators designed their analyses to assess 30-day and 1-year risk of recipient death following transplant.

Initial assessments revealed donor hearts from 2013-2017 were older, heavier, more hypertensive, diabetic, and likely to have bused illicit drugs compared to previous years. In Cox models, results indicated the risk of death following transplant from 2013-2017 was 15% lower at 30 days (HR, 0.85; 95% CI, 0.74-0.98) and 21% lower at 1 year (HR, 0.79; 95% CI, 0.73-0.87) compared to transplants from 2003-2007. Additionally, transplants occurring from 2008-2012 had a 9% lower risk of death at 30 days (HR, 0.91; 95% CI, 0.79-1.05) and a 14% lower risk of death at 1 year (HR, 0.86; 95% CI, 0.79-0.94) than their counterparts who received transplant from 2003-2007.

“This research confirms previous data that these hearts – once considered high risk – are safe,” said Howard Eisen, MD, chair of the American Heart Association’s Heart Failure and Transplantation Committee of the Clinical Cardiology Council, who not involved in either study, in the aforementioned release. “These findings should encourage institutions who are not routinely using hearts from drug users to do so. It will reduce the waiting time and the number of deaths among people on the heart transplant waitlist.”

Intoxicated Donors and Heart Transplant Outcomes,

National Trends in Heart Donor Usage Rates: Are We Efficiently Transplanting More Hearts?”

Journal of the American Heart Association, 

Despite the notion they are unsafe, a pair of studies demonstrate there were no significant differences in outcomes among heart transplant recipients receiving a donor heart based on a history of illicit drug use or overdose.

Donor Hearts from Drug Users Safe for Transplant, Becoming More Common

Leveraging information from 8 databases across the US, Germany, and South Korea, researchers from Columbia University Irving Medical Center are providing clinicians with insight into the head-to-head effectiveness and safety of ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs).

Assessing more than 50 outcomes among a multinational cohort of more than 2.9 million 

, investigators found both classes exhibited similar efficacy in reducing cardiovascular events but use of ARBs was associated with fewer adverse events, including tissue swelling, pancreas inflammation, cough, and others.

"In professional guidelines, several classes of medications are equally recommended as first-line therapies. With so many medicines to choose from, we felt we could help provide some clarity and guidance to patients and health care professionals," said lead investigator RuiJun Chen, MD, Assistant Professor at Geisinger Medical Center in Pennsylvania and Postdoctoral Fellow at Columbia University at the time of the study, in 

a press release from the American Heart Association

With both classes recommended as first-line treatment for hypertension but an apparent lack of head-to-head studies comparing them, Chen and colleagues sought to assess the efficacy and safety of ACE inhibitors versus ARBs using real-world data. With this in mind, investigators designed their study as a retrospective, new-user comparative cohort analysis using data from 8 databases collecting information from 1996-2018 within the US, Germany and South Korea.

The specific databases used in the study were the IBM MarketScan Commercial Claims and Encounters database, IBM MarketScan Medicare Supplemental Beneficiaries database, IBM MarketScan Multi-state Medicaid database, Optum De-Identified Clinformatics Data Mart Database, Korea National Health Insurance Service/National Sample Cohort, IMS/ IQVIA Disease Analyzer Germany, Columbia University Irving Medical Center database, and the Optum De-Identified Electronic Health Record Dataset.

For inclusion in the investigators’ analyses, patients were required to have at least 1 year of prior observation in the database before treatment initiation, have a recorded diagnosis of hypertension at the time of initiating therapy or during the year prior, not have been previously exposed to any antihypertensive medication, and not initiate another antihypertensive therapy within 7 days of index exposure to an ACE inhibitor or ARB.

Investigators assessed for 55 total outcomes, including 4 primary efficacy outcomes and 51 secondary outcomes. The primary outcomes of interest were acute myocardial infarction (AMI), hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite of the aforementioned cardiovascular events. Secondary outcomes were mostly safety-based and were based on known or suspected side effects of antihypertensive medications.

From the databases, investigators identified 2,297,881 patients initiating therapy with an ACE inhibitor and 673,938 initiating treatment with an ARB. Overall, 39% of the patients were female, 175 had diabetes, 37% had hyperlipidemia, and 9% had a history of cardiovascular disease. The most commonly used ACE inhibitor was lisinopril (80%) and the most commonly used ARB was losartan (45%).

In adjusted analyses, investigators observed no statistically significant difference in AMI (HR, 1.11; 95% CI, 0.95-1.32), heart failure (HR, 1.03l 95% CI, 0.87-1.24), stroke (HR, 1.07; 95% CI, 0.91-1.27), or the composite cardiovascular outcome (HR, 1.06; 95% CI, 0.90-1.25) for patients using ACE inhibitors compared to ARBs. For safety outcomes, investigators pointed out significantly lower risks for angioedema (HR, 3.31; 95% CI, 2.55-4.51; 

 <.01), cough (HR, 1.32; 95% CI, 1.11-1.59; 

 <.01), acute pancreatitis (HR, 1.32; 95% CI, 1.04-1.70; 

A retrospective cohort study with data from nearly 4 million patients with hypertension from the US, Germany, and South Korea found ACEs and ARBs provide similar efficacy for prevention of cardiovascular events, but ACEs were associated with a greater risk of adverse events. 

Donor Hearts from Drug Users Safe for Transplant, Becoming More Common

ACEs & ARBs Similar in Event Prevention, But ARBs Have Favorable Safety Profile

Q&A on Heart Failure Prevention, with Javed Butler, MD

Assessing Prepregnancy CV Risk Factors Could Help Identify Heightened Risk of Adverse Outcomes for Mother, Offspring

DAPA-CKD Analysis Suggests Farxiga is Safe, Effective in More Advanced Chronic Kidney Disease