AHA 2018: New Cholesterol Guidelines, Fish Oil, Diabetes Meds, and Inflammation Blow Into the Windy City

Hold onto your hats if you’re heading to the Windy City for the American Heart Association (AHA) 2018 Scientific Sessions: this year’s program is serving up nearly 30 late-breaking clinical trials (LBCTs), crammed into its new, much-ballyhooed 3-day format.

Joining the American College of Cardiology (ACC), which shortened its annual conference to 3 days back in 2013, the newly “shrunken” AHA meeting is taking place November 10-12.

“We think for both the presenters and attendees, this new format is going to be lively, exciting, and consistent with where news and displays of scientific meetings should be going in the future,” Eric Peterson, MD (Duke Clinical Research Institute, Durham, NC), chair of the AHA’s Scientific Sessions programming committee, told reporters on a telebriefing last week.

“They will be full days, but I think we’ve packed in some really exciting science and a lot of really important clinical information is going to be imparted as well,” committee co-chair Donald Lloyd-Jones, MD (Northwestern University, Chicago, IL), chimed in. “Not only new science but also new management [and] new practice opportunities for clinicians to really hone their skills with.”

Those comments were in part a nod to the two new ACC/AHA guidelines that will be released at this year’s meeting: the 2018 Cholesterol Clinical Practice Guidelines, on Saturday morning, and the Physical Activity Guidelines for Americans, on Monday morning. The cholesterol guidelines represent the first update to this document since the quite controversial 2013 version was released.

According to Lloyd-Jones, who is also a co-author on the cholesterol guidelines, there are two major themes to watch for in the 2018 update. The first involves recommendations specific to the two PCSK9 inhibitors, Food and Drug Administration (FDA)-approved in the intervening years. The second theme concerns how to better select patients for cholesterol-lowering therapies. 

“There’ve been questions about when should we use risk scores, are there some risk scores that are better than others, or are there strategies of risk assessment that we should be deploying beyond risk scores? This is an area of much discussion in the guidelines, and I think you’ll see some pretty significant advances in terms of how we think about patients and who might be appropriate for using statin therapy and who might be appropriate for withholding statin therapy because it’s unlikely they will benefit,” Lloyd-Jones said.

As for the physical activity guidelines, this is their second edition, the first having been issued a decade earlier. “Since 2008 there’s [been] a greater understanding of both the quantity and types of activities that seem to have particular benefits,” Lloyd-Jones observed. “The guideline writers will have specific recommendations that can help guide people in their selection of the types, intensity, and frequency of their physical activity and these will be specifically outlined in that guideline.”

Late-Breaking Clinical Trials

During the press briefing, Peterson zeroed in on perhaps a dozen of the 28 LBCTs spread across six sessions slated for presentation at AHA 2018. “To be honest with you, it was tough to choose which to highlight over the others,” he said.

Of note, the late-breaking sessions will be three per day, Saturday and Sunday, with no late breakers scheduled for Monday.  

Topping Peterson’s list were VITAL, the long-running, 25,000-patient National Institutes of Health study looking at vitamin D and fish oil supplements for cardiovascular disease prevention, plus REDUCE-IT, another fish oil study, this one using the highly purified, “pharmaceutical grade” ethyl ester of eicosapentaenoic acid. Both studies are part of the first late-breaking session, on Saturday afternoon, titled “Answers to Critical Questions in CV Prevention.” Topline results from REDUCE-IT have already been released touting a significant reduction in the risk of hard cardiovascular events among statin-treated patients taking a 4-mg daily dose of the omega-3 pill, as compared with placebo.

“This will be an exciting study, to see the details behind that,” Peterson commented.

Also part of that initial Saturday LBCT session is the Japanese EWTOPIA 75 trial, Peterson noted. This 6,000-patient study is testing ezetimibe to prevent cerebrovascular and cardiovascular events in middle-to-high-risk adults 75 years and older who have elevated LDL cholesterol.

Another AHA late breaker for which topline results have already been released is DECLARE-TIMI 58, part of Saturday’s LBCT 2 grouping (“Novel Approaches for CV Prevention”) and on Peterson’s shortlist. As reported by TCTMD, the trial, conducted in diabetic patients at high risk for CVD, met one of two co-primary efficacy endpoints. It demonstrated a reduction in a composite of CV death or hospitalization for heart failure with the selective sodium glucose co-transport 2 (SGLT-2) inhibitor dapagliflozin (Farxiga; AstraZeneca) versus placebo, but it failed to show a significant difference in MACE (CV death, MI, or ischemic stroke).

As Peterson pointed out during the telebriefing, DECLARE-TIMI 58 is the third trial to examine hard cardiovascular outcomes with this class of diabetes drugs following EMPA-REG OUTCOME and CANVAS—the former being “very positive” and the second “having good results, but also having some side effects that were concerning.” This third trial will provide some clarity for the class as a whole, Peterson continued, particularly since it was conducted in patients with diabetes but without preexisting cardiovascular disease.

“If this study is as definitive as people have potentially thought it could be, it could make this class of drugs much more standardly used,” in diabetes patients with, or at high risk for, cardiovascular disease, he said.

Peterson additionally highlighted two other trials in this second Saturday session: CIRT, testing low-dose methotrexate for the prevention of atherosclerotic events, and Yoga-CaRe, a 4,000-patient randomized clinical trial evaluating yoga for cardiac rehabilitation in patients following acute MI. CIRT is notable in the wake of news that the FDA had declined to grant a cardiovascular indication to canakinumab (Novartis) , a fully human monoclonal antibody that, like methotrexate, targets part of the inflammatory pathway. Unlike canakinumab, which is an expensive orphan drug, methotrexate is inexpensive and available as a generic. CIRT, funded by the National Heart, Lung, and Blood Institute (NHLBI), was stopped before reaching its target enrollment of 7,000 patients, although no significant safety signals were seen.

LBCT session 3, also on Saturday, groups five trials deemed to be “harnessing technology and improving global health.” LBCT 4, on Sunday morning, includes five trials geared towards “preserving brain and heart in acute care cardiology.” Notable for interventionalists in this batch (although not highlighted by Peterson) are T-TIME, a randomized, double blind, placebo-controlled, parallel group, multicenter clinical trial of low-dose adjunctive alteplase during primary PCI; EARLY, examining early or delayed revascularization for intermediate and high-risk non-ST-elevation acute coronary syndromes; and the Door-to-Unloading pilot trial, looking at mechanically unloading the left ventricle using the Impella CP system (Abiomed) and delaying reperfusion in patients with anterior ST-segment elevation MI.

LBCT 5 is dedicated to “hot” heart failure trials. In this group, Peterson singled out TRED-HF, a small, pilot study testing the safety and feasibility of stopping medical therapy in patients with recovered dilated cardiomyopathy.

LBCT 6 is devoted to late-breaking science in coronary revascularization and includes two CABG studies and one study of intramyocardial mesenchymal cells in heart failure, plus long-term outcomes from both the FREEDOM study (CABG versus PCI in patients with diabetes and multivessel disease) and ISAR-TEST 4, comparing DES with biodegradable versus permanent polymers out to 10 years.

Beyond the Late Breakers

During the press telebriefing, Peterson and Lloyd-Jones offered tips for other agenda items beyond the late-breaking and guidelines sessions.

Peterson noted that this year’s meeting has done away with the traditional presidential address followed by “a long series of awards” and is instead opening “with a bang—a series of TED-like lectures.” These talks will tackle eight of the “hottest things in science” and cardiovascular medicine: everything from whether an individual’s “microbiome” affects cardiovascular disease risk to the potential for vaccines to prevent against cardiovascular diseases.

There is also a whole “health tech track,” Peterson continued, exploring “how health technology—be it electronic medical records, your cell phone, other mobile wearable devices—can help us as clinicians better understand what’s going on with CVD and then help us as individuals actually try to modify our risk factors as a function of time.” Part of the exhibit floor is dedicated to this track as well as programming focused on digital and wearable devices, he added.

Lloyd-Jones, by contrast, zeroed in on sessions dealing less on futuristic themes and more on entrenched problems. A Saturday late-afternoon session entitled: “Are Zip Codes More Important than Genetic Codes?” is addressing issues of social and environmental determinants of health. A Monday morning session called “Unpacking the Cardiovascular Biology of Violence” delves into the impact of physical trauma on the heart.

Lloyd-Jones also gave a shout-out to what the AHA has called a “historic summit” dubbed “Bethesda +40” recognizing the 40th anniversary of the Bethesda Conference on the Declining Mortality from Coronary Heart Disease. As Lloyd-Jones reminded reporters, the NHLBI convened the original Bethesda Conference in 1978 to make sense of the rapidly declining rates of CVD mortality in the US and across the globe, but that decline came to a halt in 2010.

“The NHLBI wants to reconvene a similar conference to understand the loss of that decline and now the stagnation of cardiovascular disease death rates, and to try to get to a place where we can reenergize and reignite these declines by pursuing a research agenda that will help us understand where we are and where we need to go,” he said.

One final novelty worth noting at this year’s AHA: the meeting has severed ties—at least geographically—with the Resuscitation Science Symposium, which will be held at a different location (3 miles away) from November 10 to 11.

TCTMD reporters Todd Neale, Michael O’Riordan, Yael Maxwell, and I will be covering the meeting live from Chicago’s McCormack Place. Bookmark TCTMD on your mobile device or follow us on Twitter for breaking news and updates.

Editor's Note: An earlier version of this story erroneously listed the LEADER trial as one of the first CVD outcomes trial with the SGLT2 inhibitor class of drugs.