November 03, 2015

ORLANDO, FL — Their names are legendary: Universal Studios, SeaWorld, Walt Disney World, and—also rarely mentioned by heartwire from Medscape—Wet 'n' Wild and Gatorland. But next week the hot tickets in central Florida are to the American Heart Association (AHA) 2015 Scientific Sessions, which graces the area only every few years.

And while they may not feature orcas or an anthropomorphic mouse, the AHA sessions give center stage to hundreds of late-breaking clinical-trial (LBCT) presentations and other oral and poster reports, tutorials, lectures, and interactive learning exhibits. For fans of clinical-trial acronym quirks, the meeting even features two trials with different goals but the same moniker: BEAT-HF, a trial of a  beta-3 agonist therapy and a test of a wireless remote-monitoring strategy.

But the single-study LBCT 5 (2:00 pm November 9), with 75 minutes devoted to its presentation and discussion on Monday of the sessions,  may be the top trial presentation of the week, laying claim to the title in part because of the anticipation unleashed when its top-line results became public in September. In the National Institutes of Health-funded Systolic Blood Pressure Intervention Trial (SPRINT), high-risk hypertensive patients benefited with significantly reduced cardiovascular event risk and all-cause mortality when treated to a systolic-blood-pressure target of 120 mm Hg rather than 140 mm Hg.

Dr Eric Peterson

"If the trial results are as good as they say they are in the initial reports, it really changes how I practice. I'm going to have to push harder to get people significantly lower than we have before," AHA sessions program cochair Dr Eric Peterson (Duke Clinical Research Institute, Durham, NC) told heartwire .

"We had gotten pretty comfortable with high blood pressure, thinking that it was okay to have somebody in a certain 140-to-150 range," while the guidelines "have become, if anything, more lenient," observed Peterson. SPRINT, he said, could have a huge impact on a national scale.

Other session highlights:

LBCT 1
, Sunday, November 8, 2015, 3:45 pm

Leading off a wide range of heart-failure presentations, a randomized trial explored use of the glucagonlike peptide-1 (GLP-1) agonist liraglutide (Victoza, Novo Nordisk), a mainstay antidiabetic agent, in a high-risk heart-failure population regardless of diabetic status. Its 300 patients with a recent history of hospitalization for acute heart failure were followed for mortality, heart-failure hospitalizations, and natriuretic peptides, among other variables. The study is a great demonstration of how traditional anatomic and pathologic definitions of disease "really are breaking down in the era of molecular medicine," according to Peterson. "It really is more about the mechanisms and the receptors than it is about classic disease states."

The next presentation is on the randomized Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction (NEAT-HFpEF) trial, which is looking at isosorbide mononitrate's effect on accelerometer-measured daily-activity levels in 110 patients with preserved-EF heart failure. That's followed by the Soluble Guanylate Cyclase Stimulator In Heart Failure Patients with Reduced Ejection Fraction (SOCRATES-REDUCED) study with more than 400 patients, looking at the of effects vericiguat (Bayer Healthcare/Merck), a soluble guanylate cyclase (sGC) stimulator, on natriuretic-peptide levels and tracking adverse events.

Then, the randomized Better Effectiveness After Transition—Heart Failure (BEAT-HF) study explored the use of wireless remote monitoring with structured telephone check-ins in >1400 patients who had been hospitalized with heart failure, following them for 6 months. "Ultimately, care transitions and the management of patients is probably as important as having some new agent to treat patients with," Peterson said. "If the study does show some promise, it will indicate that again, more contact with patients and better connections with patients in their home environment can result in better outcomes."

LBCT 2
, Monday, November 9, 2015, 10:45 am

The second late-breaking trial set begins with smoking cessation in a special population, those hospitalized with acute coronary syndromes. About 300 such patients, active smokers when hospitalized, were randomized prior to discharge to a smoking-cessation program based on varenicline (Chantix, Pfizer) or placebo. The challenge, Peterson observed, is that smoking cessation is extremely effective at helping to prevent further events in ACS patients, "but we also know we do a lousy job of getting patients to quit."

Slated for presentation afterward, the Myocardial Infarction Genes (MI-GENES) study takes the world of genomics and explores the human element: if patients are informed of their coronary-disease risk based on genomic testing, "will that information actually affect behavior and management of those patients and ultimately lead to lower LDL?" Peterson asked. "This is on the very edge of personalized medicine. If you know your genes, if you know you have this predisposition, will you be more aggressive in terms of how you modify your risk factors?"

Also on the bill is the EMPA-REG OUTCOME study, "a deeper dive into the results" compared with what was presented recently at the European Association for the Study of Diabetes 2015 Meeting, observed Peterson. The ground-breaking results—a 38% drop in CV mortality risk and 32% decline in all-cause mortality in diabetics who took the glucose-lowering agent empagliflozin (Jardiance, Boehringer Ingelheim/Lilly)—wowed attendees at that mid-September congress. But the presentation didn't give much attention to effects in predefined subgroups, including patients with heart failure. The analysis at AHA will be in a sense tailored for cardiologists, he said.

The lineup of trials also includes Peer-Group-Based Intervention Program (Fifty-Fifty) randomized trial of ways to promote change in cardiovascular risk behaviors. Also, the Make Better Choices (MBC2) trial is a randomized exploration of whether self-monitoring of health behaviors using smartphone apps, which automatically transmit the data to behavior coaches, can lead to improvements in diet and activity levels over 1 year.

LBCT 3
, Tuesday, November 10, 2015, 10:45 am

The session leads off with Providing Rapid Out-of-Hospital Acute Cardiovascular Treatment (PROACT-4), a "troponins-in-the-field" trial, Peterson said, that is looking at the prehospital use of high-sensitivity troponin triage and natriuretic-peptide testing vs no prehospital biomarker tests in about 600 patients with suspected acute ST-segment-elevation MI. The primary end point is time from first medical contact to final patient disposition—that is, establishment of a plan for discharge from the emergency department or hospital admission.

Primary results of the Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (RIVER-PCI) were reported last month at TCT 2015 and showed no gains from taking ranolazine (Ranexa, Gilead Sciences) in patients with chronic angina after incomplete-revascularization PCI. The LBCT 3 session will feature a quality-of-life analysis and is more about the effects of complete vs incomplete revascularization than ranolazine, according to Peterson.

Also on tap is a long-term tolerability analysis based on the PEGASUS-TIMI 54 trial, of which the primary analysis had been presented at the American College of Cardiology 2015 Scientific Sessions and simultaneously published. It had compared treatment with ticagrelor (Brilinta, AstraZeneca) plus aspirin vs aspirin alone for secondary prevention. It had seen a 15% drop in risk of MI, stroke, or CV death among patients on the dual-agent antiplatelet regimen. Following PEGASUS-TIMI 54 is a secondary analysis of the Dual Antiplatelet Therapy (DAPT), which looked at duration of dual-agent antiplatelet therapy after PCI.

LBCT 4
, Wednesday, November 11, 2015, 10:45 am

Attendees sticking around for the Wednesday half-day will be rewarded with a number of trials in novel or unusual areas. Among them is the small, phase 1, dose-ranging evaluation of a novel inhibitor of proprotein convertase subtilisin-kexin type 9 (PCSK9) called ALN-PCSsc (Alnylam Pharmaceuticals). It lowers LDL cholesterol through an RNA-mediated mechanism and isn't antibody-based like evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron Pharmaceuticals). It also differs in another possibly important way. If the study's results are in the right direction, Peterson said, "This agent could potentially lower cholesterol if given on a quarterly basis or maybe even semiannually. Can you imagine if you just had to get this agent given to you twice a year and your cholesterol could be normalized?"

The randomized, controlled Beta-3 Agonist Treatment in Heart Failure trial (the sessions' other BEAT-HF) has explored the use of mirabegron (Myrbetriq, Astellas Pharma), available in the US and Europe for overactive bladder, in patients with chronic heart failure. The trial's approximately 70 patients were followed for effects on left ventricular function, echocardiographic measures of remodeling, natriuretic peptides, and 6-minute-walk distance over 6 months.

With cardio-oncology a growing field of interest in its own right, the Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) trial will be presented during this session. It put to the test a strategy long used without much of an evidence base: standard heart-failure medications for heart failure secondary to chemotherapy cardiomyopathy. Peterson said the 130-patient randomized trial would need a much larger follow-up trial but lauded it for addressing "a really important medical question that we've been sort of stuck on." The trial, with a 2x2 randomization, is looking at the effects of dual therapy with the angiotensin-receptor blocker (ARB) candesartan and the beta-blocker metoprolol vs their respective placebos, during anthracycline chemotherapy and radiotherapy following surgery for breast cancer.

Also in the session: yet another in the ANNEXA series of trials evaluating a so-called universal antidote for factor Xa inhibitors, in this case rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals). The randomized, placebo-controlled ANNEXA-R Part 2 is a phase 3 safety and efficacy evaluation of andexanet alfa (Portola Pharmaceuticals) administered as an IV bolus followed by a continuous infusion of 8 mg/min for 120 minutes in "older, healthy volunteers." Portola released top-line results on September 3, reporting that the study "achieved all primary and secondary end points with high statistical significance."

Although the clinical value of reversal agents for the new oral anticoagulants (NOAC) has been debated, Peterson said they are important because they are often perceived as necessary. "It's not a matter of whether there will be a huge market for them," he said. That reversal agents weren't available for a long time was a factor in physician-patient discussions about NOAC use. "It's one reason people often give for not using these newer agents."

Other Amusements: Health Tech, Genomics Boot Camp

"There is a whole session devoted to something near and dear to my heart, Health Tech: wearable devices, mobile apps, and so on," Peterson said, referring to a series of presentations and activities taking place throughout much of Monday, November 9. "They will talk about the frontiers, including whether it should be regulated and how do we get practices and providers to adopt them." There will also be what Peterson described as "a Shark Tank–like competition, "where the latest and greatest are showing their wares. It should be neat, because, if you think they're taking off in the general world, physicians have been slow to see this coming."

The Genomics Boot Camp occurs in several sessions across the week. "There are a huge number of new [genomic] markers out there, and physicians are really not well equipped to know who and what and where to integrate them into their clinical practice," according to Peterson. Some of the presentations will be oriented toward clinical practice, others toward the research community, he said. One of the boot camp's goals is to raise awareness about the field, with recent realization that the genomics-based tools and strategies already available "that should be affecting the mainstream haven't yet been absorbed by the mainstream."

Finally, Peterson noted, the globalization of the AHA sessions going on for many years continues to reach new heights. "Up to a third of our faculty is international, and up to 50% of the science being presented is international. So the American Heart Association meetings are much more the 'Heart Association' meetings now."

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