This year's gathering of the American Heart Association happens in New Orleans, LA. It's been a while since cardiology has visited this iconic American     city.

AHA is known for its broad scope into all aspects of heart-disease treatment—from basic science through public health. Studies range from intracellular     molecules to sugary drinks.

Day 1: "Big Trials for Big Questions"

A huge question is whether there exists a cardiovascular safety difference among NSAIDs. Dr Steven Nissen (Cleveland Clinic, OH) will present the     10-year long PRECISION trial,[1] a multinational double-blind and triple-dummy randomized controlled trial (RCT) that compares     celecoxib, ibuprofen, or naproxen in more than 24,000 subjects with osteoarthritis or rheumatoid arthritis and a known history of CV events or CV risk     factors. Even if the between-drug differences are small, the large numbers of people with both heart disease and orthopedic disease make these results     important from a public-health perspective.

Cognition is a massively patient-centered outcome. Little talked about when the HOPE-3 trial,[2]     an RCT that studied primary-prevention therapy of intermediate-risk subjects (n=12,705) with statins and/or blood-pressure–lowering agents, was presented     earlier this year was its cognition arm, which we’ll learn about at the AHA meeting. HOPE-3 showed that blood-pressure therapy did not alter outcomes, but     treatment with rosuvastatin at a dose of 10 mg per day reduced cardiovascular events more than placebo. Reasonable people worry that excess lowering of     cholesterol and blood pressure might worsen brain function. We shall see. Good on the Canadian investigators for including this end point.

One of the first lessons in cardiology is that early and brisk decompression of the heart during acute heart failure—preload and afterload reduction, if     you will—is key. The novel compound ularitide is a chemically synthesized form of the human natriuretic peptide urodilatin. And urodilatin is produced in     humans by differential processing of pro-atrial natriuretic peptide in distal renal tubule cells. In the last late-breaker of the first day, Dr Milton Packer (University of Texas Southwestern Medical Center, Dallas) will present results of the phase 3 study called    TRUE-AHF—an RCT performed in 190 centers in the US, Europe, Canada     and Latin America—that will compare placebo or ularitide for 48 hours in addition to standard care in more than 2000 patients with acute heart failure.[3]

Day 2: Pioneering the Future of Heart Interventions

Although my interventional colleagues relentlessly reduce the number of patients requiring CABG, surgery remains a vital option: witness the    EXCEL and NOBLE trials.[4,5] If your patient chooses or is best suited for bypass surgery, should the surgeon use a single or bilateral mammary artery conduit? The Arterial Revascularization Trial (ART) is a randomized comparison of bilateral internal mammary artery     vs single internal mammary artery grafting in CABG, and it is one of the largest randomized trials of surgery ever conducted. At the AHA, we will learn the     5-year results of more than 2100 patients.[6] I love RCT data from cardiac surgeons. Please keep it coming.

In the cath lab, injection of contrast does a good job of showing the lumen of arteries. The problem is that monitors are one-dimensional and the artery is     three-dimensional. French investigators decided to test the strategy of using fractional flow reserve (FFR) to guide the decision to intervene. The             FUTURE         trial compared clinical outcomes and cost-effectiveness of two therapeutic strategies, one based on coronary angiography guidance and the other based on     coronary angiography with FFR in patients with multivessel coronary artery disease.

Dr Michael Gibson (Beth Israel, Boston, MA) will present the    PIONEER AF-PCI trial—an RCT that studies the increasingly     relevant question of treating patients with AF who undergo PCI. This trial evaluates the safety of two rivaroxaban (Xarelto, Bayer/Johnson &     Johnson) treatment strategies and one vitamin K antagonist (VKA) treatment strategy utilizing various combinations of dual antiplatelet therapy (DAPT) comprising low-dose aspirin with clopidogrel (or prasugrel [Effient, Daiichi Sankyo] or ticagrelor [Brilinta, Brilique, AstraZeneca]). Good. I'm glad. We need more evidence in this     scenario.

Germany has led the way in use of the transcatheter aortic-valve replacement (TAVR). The    German Aortic Valve Registry (GARY) reported     acute results and complications of nearly 16,000 TAVR recipients in the Journal of the American College of Cardiology in 2015.[7] At the AHA     meeting, we will hear about the 1-year outcomes of intermediate surgical risk patients in this large registry. You know the story: as TAVR is gradually     performed on lower-risk patients, patients who do beautifully with surgery, outcomes and valve durability with TAVR will have a higher bar to exceed.

Day 3: Insights From New Therapeutic Trials for Lipids

PCSK9si is a first-in-class investigational medicine that acts by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis in the liver     via RNA interference. The drug can be given quarterly or biannually. On October 18, in a press release, the Medicines Company announced top-line results from the interim analysis at day 90 follow-up for 501 patients enrolled in the ongoing    ORION-1 study. We will hear these results during the third day of late-breaking science.

Evolocumab (Repatha, Amgen) dramatically lowers LDL cholesterol. This we know. What about other surrogates? Dr Nissen will present the results of the    GLAGOV study, which is the first     trial to assess the effects of a PCSK9 inhibitor on the regression or progression of atherosclerosis in subjects undergoing cardiac cath. Subjects will be     assessed by intravascular ultrasound at baseline and then again at 78 weeks. Top-line results show     that evolocumab met the primary end point of change in percent atheroma volume from baseline to week 78 compared with placebo. It’s still not an outcomes     trial, but  the drug shows regression of arterial disease as measured by actually looking at the vessel, which is notable.

Like Dr Nissen, Dr Gibson has another trial to present. AEGIS-1 is a phase     2b multicenter, randomized, placebo-controlled, dose-ranging clinical trial that studies the safety and tolerability of multiple administrations of two     dose arms of CSL112 in patients who had MI. CSL112 is a reconstituted formulation of apoA1, the     main component of HDL, derived from human plasma and reconstituted to form HDL particles suitable for infusion. The hope is that by rapidly raising HDL     levels, CSL112 will quickly reduce cholesterol-loaded plaques that contribute to cardiovascular events.

Genetics seems to lead the way in new lipid studies. ANGPTL3 is an interesting target for the management of both plasma triglycerides and cholesterol. We     know from genetic studies of patients who are heterozygous for loss-of-function mutations in their ANGPTL3 gene that they have half-normal levels     of plasma ANGPTL3 and, correspondingly, lower levels of plasma triglycerides and cholesterol. In the fourth late-breaking sessions, Dr Teresa Brandt from Ionis Pharmaceuticals will present an early study on the safety, tolerability, pharmacokinetics, and pharmacodynamics of    IONIS ANGPTL3-LRx (antisense inhibitor against ANGPTL3) in healthy volunteers with elevated     triglycerides.

The final study in this session takes as its goal the mimic of residents of a Northern Italian village who remarkably have little atherosclerotic buildup     despite exceptionally low levels of HDL and elevated levels of triglycerides. South Australian researcher Dr Stephen Nicholls will present the results of     the MILANO-PILOT trial, a proof-of-concept, double-blind,     placebo-controlled, randomized study utilizing intravascular ultrasound (IVUS) to measure the effect of MDCO-216 on atherosclerotic plaque burden and to     evaluate MDCO-216's impact on cholesterol efflux. In case you didn't know, I surely did not: MDCO-216 is a complex of dimeric recombinant apolipoprotein A1     Milano that mimics pre-beta HDL and induces cholesterol efflux, which is the first step in the reverse cholesterol transport, a process of removal of     deposited cholesterol from vessel walls. All this biology could have the potential to reduce plaque burden in patients with coronary artery disease.

Day 4: Guiding the Momentum to Effect HF Outcomes: Ironing Out the Wrinkles

A trend from major cardiology meetings: the last day of late-breaking trials tend to deal with heart-failure outcomes, this one moderated by Dr Clyde Yancy (Northwestern University, Chicago, IL).

I've already spoken about reducing pressure in the heart during acute heart failure. But that was with drugs.    Corvia Medical has another idea. It has designed a device that creates and maintains a permanent atrial     shunt device—so that blood is shunted from the high-pressure LA to the RA. I know, this sounds dodgy; what could go wrong? But let's keep an open mind. Researchers have already published encouraging results of a phase 1 feasibility study in the Lancet this year.[8] At the AHA meeting, Dr David Kaye (Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne, Australia) presents the 1-year results of the    REDUCE LAP-HF trial in patients with preserved or     mildly reduced ejection fraction.

Everyone agrees spironolactone is extremely useful and probably underused in the treatment of patients with heart failure. One issue with the inexpensive     drug is dosing. The ATHENA-HF[9] trial will test the hypothesis     that high-dose spironolactone will lead to greater proportional reduction in NT-proBNP levels from randomization to 96 hours over standard of care. Good.     We need more data on this. I suspect we often underdose the drug.

Endurance athletes perform better with more oxygen-carrying capacity in the blood. Why wouldn't patients with heart failure? Researchers from Boston and the Netherlands will present two separate studies addressing the potential benefit of iron supplementation for patients with heart failure. The    IRONOUT HF trial studies the effect of oral supplementation on change in peak VO2 in a broad population of patients with HFrEF while the Dutch study,    EFFECT-HF , looks at the effect of IV iron therapy     in patients with chronic heart failure.

In the MOMENTUM-3 trial, Dr Mandeep Mehra(Brigham and Women's Hospital,     Boston, MA) will present data comparing HeartMate 3 with HeartMate II at 6 months for stroke-free (modified Rankin scale >3) survival without pump     replacement. I'm no LVAD expert, but I wouldn't bet against the newer device looking better.

Some other studies to keep an eye on:

Heart-failure outcomes: In a session titled "Hospitalization and Readmission for Heart Failure: Rethinking Recurrent Events,"authors with the Get With the     Guidelines-Heart Failure program will present data on the association of     risk-adjusted 30-day heart-failure readmission under the hospital-readmissions–reduction program. There's going to be a lot of talk about     heart-failure-outcome measures. I, for one, think worshiping readmissions as a measure distracts us from other patient-centered outcomes—say, for instance,     symptom relief, reduction of pill burden, and overall burden of medical care.

Generic drug prices:When a drug goes generic, it's supposed to be low cost—predictably and consistently low cost. A group of researchers from St Louis     University, led by Dr Paul Hauptman, will present data looking at the retail     pricing for three generic CHF drugs. Their findings could have important implications—both for individual and public health—as adherence to heart-failure     drugs is associated with improved outcomes. While the late-breaking trials focus on new science, this sort of research informs basic patient care—the kind we     do today and tomorrow.

Does diagnosing coronary disease change outcomes?     Coronary CT angiography (CCTA) sounds like a good idea, right? It's noninvasive and quite sensitive. You see the disease, and that's good. Dr Andrew Foy is a rising star in cardiology and outcomes research. He and colleagues, including this opinion writer, will present a    meta-analysis of published studies that show CCTA increases invasive procedures     but does not improve clinical outcomes. This is a crucial concept because it supports the oft-forgotten truth that atherosclerosis is a systemic not focal     disease.

Nutrition: I was serious about sugary drinks. Researchers from my medical school alma mater, the University of Connecticut, will present the    results of a public-health advocacy movement to promote better beverage     choices. This is an important topic because sugary drinks are a leading contributor to the diseases of the next generation—obesity, diabetes, hypertension,     immobility, and atrial fibrillation. There's a lot of wrangling in the nutrition world about low-fat or low-sugar diets. I see this as fine tuning. The big     returns will come with reducing consumption of processed food and sugary drinks—ie, junk food.

We will see you in New Orleans. The news and feature team from the theheart.org on Medscape will provide complete and timely news     coverage.

JMM

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