DocTalk Podcast: 2019 in Review with Deepak Bhatt, MD, MPH

With the conclusion of the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia the last major cardiology meeting is behind us, it is safe to say it has been a big year in heart health.

From new guidelines to new therapies to new drug classes, every major conference has brought us new trials and information that will have tangible impact on real-world practice for years to come.

The end of 2019 also marks a bigger transition—one to a new decade. From the rapid onset of wearable technology to the expansion of SGLT2 inhibitors into the cardiovascular space, the world of cardiology has seen incredible advances from 2010 through 2019.

For more insight into how the biggest cardiology news in 2019 has shaped the ongoing landscape of the field, MD Magazine® connected with Deepak Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, over the phone following AHA 2019.

That conversation is the subject of our latest edition of the DocTalk Podcast: A Year in Review: Cardiology in 2019 with Deepak Bhatt, MD, MPH.

MD Mag: Hello and welcome to this special AHA wrap-up edition of the DocTalk Podcast. On this special edition of the DocTalk podcast, you'll be listening to a phone conversation I had with Dr. Deepak Bhatt, as we discussed 2019 a year in review in cardiology.

I'm joined here today with Dr. Deepak Bhatt. Dr. Bhatt, if you wouldn't mind giving our listeners a brief background on who you are, then we can dive into our 2019 wrap-up discussion.

Bhatt: Sure, happy to be here. I'm Dr. Deepak Bhatt. I am the Executive Director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and also a Professor of Medicine at Harvard Medical School.

MD Mag: All right, thank you for that. Now for our listeners. Dr. Bhatt and I had a brief conversation before this recording started and I decided to ask him about what I think are the three biggest takeaways from cardiology in 2019.

That would be the REDUCE-IT trial and icosapent ethyl, dapagliflozin and all the dapagliflozin trials, and last, but not least, rivaroxaban and the COMPASS trial. So Dr. Bhatt, if you could sort of take us through them and the impact they've had on the cardiology landscape in 2019.

Bhatt: Absolutely. Well, we will go with the order that you put them in. So I think, REDUCE-IT really is a landmark study that has opened up a whole new avenue towards cardiovascular prevention. The study, as you're aware, consisted of patients that were secondary prevention, but also high-risk primary prevention, meaning diabetes, and at least one additional cardiovascular risk factor, randomized to icosapent ethyl, a highly purified prescription form of EPA, or to a placebo. Finding a 25% relative risk reduction in major adverse cardiovascular events, including a significant 20% reduction in cardiovascular death.

So, those are the main findings and the results within the USA cohort—I'll add were particularly robust, including a significant 30% reduction in all-cause mortality. I just presented that recently at the American Heart Association. So, those are the reduce it results overall in the USA. And

I think in terms of implications to physicians, there are a lot of patients the data applied to because we did study abroad array of secondary prevention indications CAD, CBD, PAD, and the primary prevention cohort, specifically high risk diabetic primary prevention. That's a lot of patients within the growing number of people with diabetes. And the range of triglycerides we studied was actually including patients that are currently believed to have normal triglycerides—that is 10% of our population have triglycerides at baseline between 100 and 150. So, I think for a variety of reasons, the trial really will have a major impact on a large number of patients.

The second topic that you'd asked me to address was dapagliflozin and some data with respect to it. It was studied into the DECLARE trial where it was found to be useful in secondary and primary prevention patients extending the SGLT2 inhibitors story from higher-risk patients to lower risk primary prevention patients still finding benefit in endpoints such as heart failure hospitalizations, and renal endpoints. So, adding to the overall SGLT2 inhibitors story. DECLARE took us down to a lower risk diabetic patient, finding benefit in the primary prevention type diabetics.

So, a real contribution there from the DECLARE study, and then there was DAPA-Heart Failure a real breakthrough—I think. It examined dapagliflozin in patients with heart failure with reduced ejection fraction, but then also examined patients without diabetes with reduced ejection fraction—finding benefits in both with respect to death or hospitalization for heart failure and really similar degrees of benefit. So beyond just showing that dapagliflozin was useful in patients with diabetes, reduced ejection fraction which other SGLT2 inhibitor studies had essentially indicated but not in this prospective way, but still, the signals were all there.

That was confirmed, but then really extending our knowledge was the nondiabetic patients from DAPA-Heart Failure, who also benefited. So this really, I think, changes the way that we think about diabetes drugs and heart failure drugs and changes dapagliflozin for sure, and potentially depending on ongoing trials, other SGLT2 inhibitors from just being diabetes drugs to being heart failure drugs—even in those without diabetes. So, a major breakthrough.

Then the final trial you to ask me to discuss was the COMPASS trial—another trial that's really changed the way we think about cardiovascular risk reduction. A trial that showed the 2.5 milligrams twice a day of rivaroxaban. So a low dose—some people call it the Maschler dose of rivaroxaban—much lower than the atrial fibrillation dose, which somewhat normal renal function would be 20 milligrams a day, but to that 2.5 milligrams twice a day when added to low dose aspirin—81 milligrams a day—is superior to aspirin alone in a pretty broad population of patients with high-risk CAD or PAD.

Of course, these strategies of antithrombotic intensification are only applicable to patients at low bleeding risk, but in that patient who is at low bleeding risk, high ischemic risk due to stable CAD or as the European guidelines now call it chronic coronary syndrome and in those with PAD and especially in those with polyvascular disease that is a high atherosclerotic burden. Those sorts of patients benefit from rivaroxaban, including significant reductions in important endpoints, such as ischemic stroke, amputations, and acute limb ischemia, cardiovascular deaths with even lower all-cause mortality.

So, in the right patients at low bleeding risk, this can be a really useful addition. So 3 different trials or I guess you could say 4 because I threw in 2 for the dapagliflozin discussion that I believe have had a major impact, not just in terms of the drugs they studied, but more broadly, the implications. They have for the field of cardiovascular risk reduction.

MD Mag: I would totally agree. I think those 3 trials have really stolen away headlines or made headlines this year for very good reason. Now before I let you go, it's hard to believe it but 2019 is almost over and we're approaching 2020, which marks the start of a new decade. What do you think has been the biggest breakthrough or advancement in cardiology in this past decade from 2010 until 2019?

Bhatt: Well, you know, in fact, I think some of what we were discussing and some of what we haven't discussed would be the biggest breakthroughs of the decade and, obviously, I was involved with REDUCE-IT but I do honestly feel it's one of the major breakthroughs of the decade, not just in terms of the drug studied icosapent ethyl that surely looked quite good in the trial, but I do you think it'll lead to a whole new class of EPA or eicosapentaenoic acid-based therapeutics.

There is a lot of other research that's going on mechanistic research, imaging research with EPA. So I really do think we're at the dawn of a new era—and much like it felt when the first statins came out when the first large trials came out—like 4S, for example. I don't think people at the time fully appreciated what was going to be the case 10 years later with respect to statins, or 20 years later.

I think it will be the same thing with EPA were REDUCE-IT looks phenomenal as far as the results. But I think there's going to be all sorts of innovation in the space, other compounds down the road that will really help us understand how this EPA-mediated risk reduction is occurring and exploited even further. So, I think we're really at the beginning of an exciting new era of risk reduction that's based on EPA-related pathways.

The second thing I'll mention is related to what we discussed with respect to DECLARE and DAPA-Heart Failure, and dapagliflozin but now speaking more broadly about cardiodiabetology. The shift in thinking where diabetes drugs are no longer just confined to hemoglobin A1c reduction but rather where we started evaluating quite rigorously in the last decade the cardiovascular effects either bad or good of diabetes drugs.

I think that is an incredible shift in our thinking. Instead of just looking at biomarker reductions, hemoglobin A1c looking at heart events, things like myocardial infarction and stroke, and importantly, throwing heart failure into that mix—previously underappreciated, but now we realize that that's at least as frequent of complication in diabetes as myocardial infarction.

So, I think this focus on ischemic outcomes, heart failure outcomes, renal outcomes, how to improve them, and of course, also keep trying to improve microvascular complications is a real shift and it's in large part due to collaborations not just clinically but in research of cardiologists and endocrinologist and nephrologists and primary care and a variety of other groups. So, really an important shift in the way we are doing research in that area and also, I hope, in the way we practice with cardiologists becoming much more involved in the care of high-risk patients with diabetes, including their diabetes medicines.

The final thing that I'll mention is this incredible evolution in TAVR as a treatment for aortic stenosis, but also more broadly, structural heart disease moving away from open-heart surgery to minimally invasive techniques and by minimally invasive I mean truly minimally invasive catheter-based techniques, and for TAVR the data are looking spectacular across the risk spectrum.

Of course, we need longer-term data and in lower-risk patients before rolling out the procedure to young people or younger people, but still the data to date have been really amazing. And I think that there will be continued advances in mitral and tricuspid valve intervention and other aspects of structural heart intervention—interventions for heart failure, for example, I think we're right at the beginning of that. So, that's an area that I think we've seen a lot of great data, but there's much, much more that will come in the following decade.

MD Mag: Thank you for that. I totally agree as well. I think when we look back at 2019 in a few years, it wouldn't be a surprise if we see it as sort of a monumental shift and where we are going in terms of treating cardiovascular conditions. And now I just want to say thank you for joining us today. It's been a pleasure.

Bhatt: Yes, it was a pleasure speaking with you. Thank you.

MD Mag: That's it for this edition of the DocTalk podcast. For the latest in AHA News and cardiology, be sure to head to MDmag.com. Thank you for listening.