ACC 2018: More PCSK9 Outcomes, Antiplatelet Insights, and LifeVest Data at Last

For the second year in a row, the American College of Cardiology (ACC) is kicking off its annual meeting by “showcasing” a large PCSK9 outcomes trial. The ODYSSEY results along with those from a range of other, smaller trials promise to be “practice-changing,” according to program planners.

ODYSSEY is the 18,000-patient randomized trial in patients with acute coronary syndromes that sponsors hope will demonstrate that alirocumab injection (Praluent; Sanofi/Regeneron) on top of maximal statin therapy reduces the composite endpoint of MI, stroke, cardiovascular death, and hospitalization for angina as compared with statin therapy alone.

Last year the ACC led off with FOURIER, the 27,500-patient study that showed evolocumab (Repatha; Amgen) significantly lowers cardiovascular events by 15% but didn’t demonstrate a mortality reduction. The high cost of the drug and low absolute difference in event rates left many feeling underwhelmed, as TCTMD reported last year. Of note, FOURIER was conducted in patients with stable coronary disease and had the addition of coronary revacularization to its composite primary endpoint.

“The ODYSSEY data will be interesting regardless of what we see,” ACC 2018 Program Chair Jeffrey Kuvin, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH), told the press during a telebriefing earlier this month. “If we see an overall mortality benefit, that’s going to [make] these drugs a lot more interesting. If the data are quite similar to FOURIER, and if we see . . . no impact on mortality, that’s going to reinforce a lipid-lowering pathway that some of our patients will benefit from. Regardless of what the data show, there will be further discussion about who will benefit and in whom they will be prescribed.”

Joining ODYSSEY in what organizers call the “Opening Showcase” is the VEST trial, eagerly awaited not because the therapy studied is novel, but rather because VEST is the first large, randomized clinical trial for the LifeVest wearable cardioverter-defibrillator (Zoll Medical), approved in the US and Europe more than a decade and a half ago.

Conducted at 100 trial sites in four countries, VEST enrolled over 2,000 patients who LVEFs of 35% or less after admission and treatment for myocardial infarction. Patients were randomized to 3 months of vest-wearing or to conventional care. The primary endpoint of the study is sudden cardiac death in those first 3 months.

According to ACC President Mary Norine Walsh, MD (St. Vincent Indianapolis Hospital, Indianapolis, IN), who also spoke in the telebriefing, “wearables” and implanted devices are a key focus of this year’s meeting. There are a range of studies—VEST being one of them—exploring “not only . . . how they work but how they can be applied in our various patient populations and whether we have the randomized data to support their use,” she said

Big Tent Trials

All told, this year’s ACC will feature 20 late-breaking clinical trials and 17 featured clinical research studies selected from a total of 125 submissions. An additional 2,719 abstracts will take the form of oral presentations, moderated posters, and traditional posters. These were selected from almost 5,000 submissions, ACC 2018 Vice-Chair Andrew Kates, MD (Washington University in St. Louis, MO), explained to the press. A number of studies beyond VEST and ODYSSEY should also make headlines this year, Kates predicted, no matter what they show. Among his top picks were:

• ARTEMIS, looking at whether the amount of patient co-payments for P2Y12 inhibitors after MI affects compliance and clinical outcomes.
• MOMENTUM, addressing long-term outcomes with the HeartMate 3 mechanical circulatory support device (St. Jude Medical), a “frictionless” magnetically levitated, centrifugal, continuous-flow pump, in patients with advanced heart failure.
• ANNEXA-4, studying the use of a factor Xa inhibitor reversal agent, andexanet alfa (AndexXa; Portola Pharmaceuticals), for acute major bleeding. Preliminary results from the study were first released at the European Society of Cardiology 2016 meeting. Andexanet alfa is still under review by both the US Food and Drug Administration and the European Medicines Agency, with decisions anticipated later this spring.
• Two studies looking at reducing perioperative cardiac events among patients undergoing noncardiac surgery. One is the MANAGE study testing a NOAC, specifically dabigatran (Pradaxa; Boehringer Ingelheim), in this setting. The second—a blast from the past—is POISE, looking at 1-year outcomes following the use of perioperative metoprolol versus placebo during noncardiac surgery. The 10-year delay was due to the protracted process of obtaining 1-year data from administrative databases, despite patient consent being given at the time of enrollment, presenter Philip Devereaux, MD (McMaster University, Hamilton, Canada), told TCTMD.

“Really each of these in their own way promise to be practice-changing and just how each of these have the potential to influence practice depends on the data that gets presented,” Kates said.

Antithrombotics and Interventions

Two of the five sessions in this year’s late-breaking lineup will be of particular interest to interventional cardiologists. Sunday’s first late-breaking session—the one that includes ARTEMIS—also features two additional trials examining antiplatelet drugs in ACS. PHARMCLO compared pharmacogenomic testing with clinical judgement alone to help guide the choice of antiplatelet drug, whether clopidogrel, prasugrel (Effient; Eli Lilly), or ticagrelor (Brilinta; AstraZeneca), with a composite primary endpoint of CV death, nonfatal myocardial infarction, stroke and major bleeding at 1 year. TREAT is an international, phase III noninferiority trial comparing ticagrelor and clopidogrel in STEMI patients first treated with thrombolysis.

The final trial in this Sunday grouping, SECURE-PCI, examines whether an early 80 mg loading dose of atorvastatin prior to PCI, followed by an additional high dose within 24 hours, can reduce the rates of major cardiovascular events at 30 days in patients with ACS.

On Monday, the fifth and final late-breaking session of the meeting is dedicated to interventional cardiology. Topics include a phase II study testing a DNA plasmid (JVS-100, Juventas Therapeutics) for wound closure following endovascular procedures for critical limb ischemia and a Korean trial of PFO closure for cryptogenic stroke. There’s also SMART-DATE looking at the safety of 6-month dual antiplatelet therapy after PCI in patients with ACS. ANNEXA-4 is also included in this block of trials.

In addition, Saturday’s featured clinical research session spans some hot topics in interventional cardiology including a cost-effectiveness analysis from the DEFINE-FLAIR iFR/FFR study, 1-year outcomes with the COMBO dual-therapy stent in an all-comers population, and 5-year outcomes from the Nordic aortic valve interventions study (NOTION).

Advances in Cardiometabolic Disease

Several large trials that have made headlines at previous major meetings are making an appearance this year. These include separately presented analyses of patients with type 2 diabetes or kidney disease from the CANTOS trial of canakinumab (Novartis) and updates from two studies of SGLT-2 inhibitors, CVD-REAL and CANVAS.

Beyond the late-breaking and featured clinical research blocks, the 3-day meeting is organized into 10 different “learning pathways.” Descriptions of each on the ACC’s “plan your program” page include some suggestions for hot-button topics within each subspecialty. For example, Acute and Stable Ischemic Heart Disease has a session devoted to the ISCHEMIA and ORBITA trials. The Prevention pathway has a symposium on “hitting the moving targets” in hypertension guidance.

In a new twist, the ACC is taking pains to be more “proactive” about social media—differentiating itself from professional meetings that have discouraged or prohibited the dissemination of meeting content on Twitter and other platforms. This year the ACC has designated two “pathway tweeters”—many of them familiar to #CardioTwitter—will be using designated hashtags for each of their subspecialty topics.

“We’ve seen a growing use of social media in each meeting through the years,” Walsh said, with it becoming one of the ways that attendees get the most out of the sessions. “But we do know that not every college member can attend, so it’s a great way to be able to share science even for people who are not attending.”

The @TCTMD news team will also be tweeting at #ACC18. Follow @TCTMD_Yael, @ToddNeale, @MichaelTCTMD, @TCTMD_Caitlin, and @ShelleyWood2 for news and views from Orlando. Breaking news, big and small, can be found on our conference coverage page. Got a tip to tell me about? Let me know.