Big news awaits the cardiology community when we gather during the American College of Cardiology (ACC) 2017 Scientific Sessions in Washington, DC.

Day 1 and the Joint ACC/JACC Late-Breaking Clinical Trials

More than a decade has passed since the discovery of the gene for the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme.

During the opening showcase of late-breaking clinical trials, we will hear details of the Amgen-sponsored FOURIER[1] trial, a 27,500-patient multicenter randomized controlled trial, which assessed hard clinical outcomes for the PCSK9-inhibitor evolocumab (Repatha) in patients with established heart disease who were already taking statin drugs.

We know from a February press release that FOURIER met both its primary end point, a composite of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina or revascularization, and its secondary composite end point of cardiovascular death, nonfatal MI, or nonfatal stroke.

As if that anchoring point was not enough, Amgen has also announced that the neurocognitive substudy called EBBINGHAUS[2], after the German psychologist who pioneered the experimental study of memory, met its noninferior end point for cognitive function. Lack of cognitive impairment with super-low LDL-C levels would be a reassuring finding, but I want to see the credible intervals and the actual numbers.

FOURIER will require serious statistical translation. I see three simple questions: Are the absolute reductions in event rates clinically significant at the patient (not population) level? With 27,500 patients, a 0.5% to 1% reduction in a composite outcome will make for an impressive P value, but an NNT of more than 100 may not be persuasive to an individual patient. Second, will the drug be cost-effective? Third, and by far the more provocative, question is, will the FOURIER results settle the debate between the titrate-to-lower-LDL-C and treat-to-risk camps?

Behind the shadow of FOURIER lurk some smaller but interesting studies from day 1.  

The RESET-HCM study explores the role of exercise training in patients with hypertrophic cardiomyopathy. Good. If exercise helps people with this disease, well, that about cinches its title as the best medicine of all time.

In the matter of screening before sports participation, American doctors still wrestle over the merits of the mere ECG. No matter, the S2P Study investigators will present the results of an MRI-based screening study of more than 5000 young people.

Much noise is made about the nudge value of food-labeling formats. Whether tweaked food labels influence healthy food purchases meets a strong test at ACC—the randomized trial.

Did you know the "native South American Tsimane have the lowest levels of coronary atherosclerosis ever reported"? I did not. But that's the title of a study from St Luke's Mid America Heart Institute. Remember: the spark for PCSK9-inhibitor drugs came from the observation that people with the mutation had low levels of LDL-C and heart disease. Important clues to new therapies may be found in descriptive studies of people who do not get heart disease.

Day 2 and the Joint ACC/JAMA Late-Breaking Clinical Trials

First up on day 2 is prevention of clots in veins: The EINSTEIN CHOICE[3] study compares two doses of rivaroxaban vs aspirin for the prevention of recurrent venous thromboembolism (VTE) in patients who completed 6 to12 months of anticoagulant therapy for their index acute-VTE event.

Then we move to prevention of clots in arteries: We know triple therapy with rivaroxaban, aspirin, and P2Y12 inhibitors after acute coronary syndrome (ACS) leads to excess bleeding.[4] How about double therapy? The GEMINI-ACS-1[5] trials will estimate the bleeding risk of rivaroxaban given at low dose vs aspirin in addition to P2Y12 inhibition for patients after ACS.

Given the recent termination of the secondary-prevention COMPASS trial for benefit in one of the rivaroxaban arms, I would not bet against rivaroxaban at ACC 2017.

Of the five interventional cardiology late-breakers on day 2, my pick for most interesting is the Korean DECISION-CTO randomized trial comparing the use of drug-eluting stents vs optimal medical therapy in patients with chronic total occlusion (CTO). I worry about increasing levels of exuberance for CTO interventions. This area needs more data, and perhaps a relook at the words of Dr Bernard Lown:

"Medicine as a calling would be far better served if criteria for coronary-artery interventions were determined by issues that truly matter to patients, such as survival and long-term well-being."[6]

Day 3 Aortic-Valve Disease


ACC 2017 features many studies on the treatment of aortic-valve disease.

The issue of leaflet thrombosis remains: In 2015, publication of data from the RESOLVE and SAVORY registries[7] provoked cardiologists to consider the possibility that subclinical leaflet thrombosis in bioprosthetic aortic valves may be an underrecognized problem. We get an update on these registries on the last day of the meeting. Subclinical leaflet thrombosis is important because the turbulence it creates may shorten valve longevity. If warfarin improves the problem, bioprosthetic valves lose one of their great advantages over mechanical valves—namely, avoidance of anticoagulation.

Protecting the brain: Two studies consider neural consequences during aortic-valve interventions. One will test the value of cerebral embolic-protection devices during surgical aortic-valve replacement (SAVR). The recently published SENTINEL trial[8] found that cerebral protection used during transcatheter aortic-valve replacement (TAVR) did not lead to statistically lower neural outcomes, but the device did visually impress FDA reviewers with its ability to catch debris. Another study in this New England Journal of Medicine­–cosponsored session reports on the presence of silent cerebral microbleeds during TAVR. 

Throughout the meeting, we will hear details on real-world registry data on the treatment of valvular heart disease. These include outcomes of TAVR vs SAVR in two US registries linked to Medicare data, comparison of in-hospital and 1-year mortality for TAVR in patients with failed surgical bioprosthesis vs native aortic stenosis, and TAVR for bicuspid vs tricuspid aortic stenosis. The Medtronic-sponsored SURTAVI trial, which compared TAVR with the CoreValve system vs SAVR in patients with intermediate-risk AS, is slated for presentation as well.

Nonvalvular Disease Topics

Nonvalvular disease topics addressed in the late-breaking and featured clinical research session on day 3 include randomized clinical trials of the calcium-sensitizing agent levosimendan (Simdax, Orion) to reduce adverse cardiac events in patients with reduced ejection fraction undergoing heart surgery (the LEVO-CTS trial); uninterrupted dabigatran vs warfarin for AF ablation (RE-CIRCUIT) and a proprietary closed-loop pacing-stimulation algorithm to prevent recurrent vasovagal epidsodes (SPAIN study).

On the matter of digoxin and mortality in AF patients with and without heart failure, ARISTOTLE investigators dig into their data to tell us whether serum digoxin levels matter. My wild guess: yes, they do. We also hear news on Impella-supported outcomes of interventions in patients with acute MI and cardiogenic shock.

Two Keynote Lectures Caught My Eye

Dr David Skorton, a cardiologist by training, but now the secretary of the Smithsonian Institution, will give the Simon Dack Lecture during the opening showcase. In an era of plummeting morale among clinicians, his topic could not be more timely: "Values: How the Arts and the Humanities Nurture our Careers and Our Lives."

I am pleased that ACC organizers chose Steven Bradley from the University of Colorado to give the Douglas Zipes Distinguished Young Scientist Awardee Lecture. Dr Bradley, a cardiologist with training in epidemiology, is interested in the determinants of high-quality and high-value cardiovascular care. His lecture, "Ensuring Patients Receive the Right Therapy at the Right Time," is also timely precisely because overtreatment and waste of resources is a core cause of undertreatment and inequity of healthcare.

Our theheart.org | Medscape team will work hard to deliver the best coverage. Stay tuned.

Follow us on Twitter and Facebook. Meeting hashtag: #ACC17

 

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