Shelley Wood

October 30, 2012

LOS ANGELES — The City of Angels has seen its share of shake-ups in recent years--not the least of them being attempts to make over its downtown core. Organizers of the American Heart Association (AHA) 2012 Scientific Sessions, held in Los Angeles for the first time (and in the heart of refurbishment efforts), say there are plenty of changes and fresh ideas they hope will transform this year's meeting as well.

For starters, the program boasts a whopping 27 late-breaking clinical trials (LBCT) split across six dedicated sessions, two sessions per day, Sunday through Tuesday. In a departure from recent major meetings, very few of the studies have seen their top-line results released early for Securities and Exchange Commission purposes.

According to Dr Elliott Antman (Brigham and Women's Hospital, Boston, MA), chair of the scientific sessions program committee, a "substantial" number of LBCTs will also be simultaneously published in major scientific journals. In another departure from previous years, news embargoes for all of the late-breakers lift at the time of the individual presentations--not at the start of the session or at press conferences earlier in the day.

Grouped by theme, the first session on Sunday is dedicated to coronary artery disease and venous thromboembolism, while the second includes trials addressing health economics and quality of life (QoL). Two of the hot-button trials to watch on Sunday, according to Antman, will be featured in both of the Sunday sessions. Dr Valentin Fuster (Mount Sinai School of Medicine, New York, NY) will present the much-anticipated main results from the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, comparing PCI to CABG in patients with diabetes, in the first Sunday session at 3:30 pm PST. Then Dr Elizabeth Magnuson (St Luke's Mid America Heart Institute, Kansas City, MO) will present the cost-efficacy analysis from the same study in the second session, at 5:30 pm PST. Likewise, Dr Gervasio Lamas (Mount Sinai Medical Center, Miami, FL) will present the results from TACT, the controversial NIH trial studying chelation therapy, in the 3:30 pm PST session, while Dr Daniel Mark (Duke University, Durham, NC) will present the QoL outcomes in the later session.

Don't make the mistake of thinking the LBCT sessions will take place at the same time each day. Following hot on the heels of Sunday's late afternoon/evening sessions, Monday's LBCTs are scheduled for 9:00 and 10:45 am PST, while Tuesday's late-breakers will be unveiled at 10:45 am and 3:45 pm PST. There are no late-breaking clinical trials on Wednesday.

Omega-3s, Vitamins, and a Polypill

The first session on Monday tackles prevention of CVD, with two studies looking at omega-3 fatty acids and atrial fibrillation (Fish Oil Research with Omega-3 for Atrial Fibrillation Recurrence Delay [FORWARD] and Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation [OPERA]). The third trial in the session is the Physicians Health Study II (PHS II), looking at a multivitamin for preventing CVD. 

"Patients are attracted to this approach, because [vitamins] are over the counter, and patients somehow feel that this is less risky or toxic than a drug," Antman told heartwire . "If they turn to this and it is helpful that's a good thing, but if it's not helpful and they've [taken vitamins or supplements] to the exclusion of drugs, we need to inform them that that's not a good decision."

The fourth and final trial in the session is the Use of a Multidrug Pill in Reducing Cardiovascular Events (UMPIRE), looking at a "polypill" combination of aspirin, simvastatin, atenolol, and lisinopril or hydrochlorothiazide in patients with a previous MI or stroke.

Lipids are the focus of LBCT session 4 on Monday, with a heavy focus on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. "You are not going to see big phase 3 trials here," Antman told heartwire . "What you are going to see are new treatments for PCSK9, a completely novel way of lowering LDL quite dramatically, with antibodies to PCSK9. Are these useful in patients at very high risk--for example, those with familial hypercholesterolemia? What about in patients who are already taking statins and are well controlled? What about patients who can't take statins?" These are "difficult and subtle questions," and this group of trials "will provide information on those questions," Antman said.

Also in the lipid LBCTs is the Trial for Efficacy of Capre on Hypertriglyceridemia (TRIFECTA), looking at omega-3 supplementation in patient with hypertriglyceridemia, and dal-OUTCOMES, the 16 000-patient study of the novel cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib in patients with recent ACS. dal-OUTCOMES was stopped earlier this year after an interim analysis showed the drug did not significantly reduce CV events.

Stem Cells and LV Dysfunction

Antman pointed to a new initiative introduced by the AHA for LBCT session 4 as well as LBCT session 5, the first of Tuesday's late-breakers, on cell-based therapies in heart disease. Both sessions will open with presentations offering an introduction to the science underpinning the studies. "This will really be a state-of-the-art overview, putting things in perspective to begin the whole session," he said. As well, rather than having discussants for every trial, many of the late-breakers addressing a similar drug or topic will be discussed by a single discussant, "a departure from the standard structure" that "just makes sense," Antman said.

All five late-breakers in LBCT 5 examine stem-cell approaches in the setting of acute MI and ischemic cardiomyopathy and include both new as well as longer-term results from previously reported studies, such as Stem Cells in Patients with Ischemic Cardiomyopathy (SCIPIO).

Finally, the sixth and final LBCT session, on Tuesday, looks at drug and device therapies in heart failure. Antman made special note of the Multicenter Automatic Defibrillator Implantation Trial--Reduce Inappropriate Therapy (MADIT RIT) trial looking at high-rate cutoff and/or long delay to reduce inappropriate implantable cardioverter-defibrillator (ICD) or defibrillator-cardiac resynchronization therapy (CRT-D) responses, compared with standard programming. Also in the line-up is RELAX-AHF of RLX030 (serelaxin) in acute heart failure. In late September the trial sponsor, Novartis, announced top-line results, noting that the first-in-class agent had successfully reduced shortness of breath and all-cause mortality compare with placebo in addition to standard of care.

Special Reports and Special Sessions

Antman also highlighted the Clinical Science and Special Reports (CSSR), four sessions of 19 studies that are first-in-human or phase 2 studies of drugs and devices or registry studies. There are two CSSR sessions on Monday, one on Tuesday, and one on Wednesday. The early bird will get the worm for the first CSSR sessions on Monday and Tuesday--they start at 7:30 am PST and cover several high-interest therapies, including the EnligHTN I (St Jude Medical, St Paul, MN) first-in-human renal denervation in resistant hypertension study, on Monday, and, on Tuesday, three more studies of PCSK9 inhibition. Wednesday, when there are no late-breakers in the line-up, six CSSR studies will share the limelight, including new data from Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) and GARFIELD.

Outside the late-breaking and clinical-science sessions, Antman pointed out several "special" sessions, including a Monday 3:45 pm PST series "A Vision of the Future" on care of CVD patients. Another special session, Tuesday at 3:45 pm PST, will look at controversies in presenting and publishing data. Among the topics in this session are independent control of clinical-trial data, managing conflicts of interests, news embargoes, and open-access journals and peer review. Included on the panel for this session is Wall Street Journal reporter Ron Winslow (New York, NY).

For the first time, said Antman, the AHA meeting will host a "case theater" offering seven prerecorded procedures that can be presented and discussed, as if live, the difference being, of course, that "tapes can be stopped for an interactive discussion with the person who performed the procedure," Antman said. "In my personal opinion, this captures the key pedagogic points of the case-based teaching method in a way that doesn't put the patient at risk. [During] a live case--no matter how well you do it--you are already doing something different because you know it's live."

And, once again, the AHA is also extending scientific programming into the evening on Saturday, Sunday, and Monday nights. A light dinner is served at these events, which have unrestricted grant funding from a number of drug- and device-company sponsors. Antman emphasized that the topics and speakers are selected by the AHA program committee before sponsors are sought.

Keeping Busy and Connected

In all, this year's AHA meeting will feature over 850 sessions, up more than 100 from last year, Antman said. Of these, 376 are invited sessions and 477 are sessions dedicated to original research, both oral and poster presentations. Poster presentations will include QR codes that can be scanned by mobile devices, enabling visitors to download the poster for later viewing, listen to a short audio presentation of the data, and even participate in an online question-and-answer session with the authors.

Also on the digital front, attendees now have multiple ways of viewing and organizing this year's program, including various e-readers, Epub devices, smartphones, flip-books, and old-school PDFs.

Antman also reminded heartwire of two issues beyond the program itself. This year's meeting coincides with Election Day in the US: the Scientific Sessions homepage includes a link to the RockTheVote website, where US citizens can get information on absentee voting. According to an AHA spokesperson, the only official AHA events on Tuesday night are nine scientific council dinners, attended by about 1800 AHA volunteers. The AHA is planning to have viewing screens set up so that attendees "have the option of watching election returns."

As well, a return to standard time occurs Sunday, November 4, with the clocks falling back. "The good news is, if you forget, you won't be late," Antman said. "You'll be an hour early."