Shelley Wood

November 09, 2010

November 9, 2010 (Chicago, Illinois) — Major cardiology meetings in recent years have seen one or two specializations grab the limelight with blockbuster trial results: this year, the lineup of trials at the American Heart Association (AHA) 2010 Scientific Sessions seems to have something big for everyone. Depending on how they play out, trials across the spectrum of cardiovascular care carry the potential to change practice.

Late-Breakers: Sunday

Dr Mariell Jessup

On Sunday, the first of the four late-breaking clinical-trial sessions is dedicated to heart failure. In an interview with heartwire , program chair Dr Mariell Jessup (University of Pennsylvania School of Medicine, Philadelphia) predicted that, if positive, all four trials in the session could have a profound impact in the field.

Leading off is the RAFT trial, looking at resynchronization and defibrillation devices in patients with mild to moderate HF. "People are really going to be looking at this trial to see if there is an impact on mortality, because REVERSE and MADIT CRT didn't, they were positive, but the primary end point was driven by HF events, rather than mortality. In RAFT, if there is an impact on survival, I think that will probably push more people to start to expand the indication."

The other "big one" in this first session is ASCEND HF, looking at nesiritide in decompensated HF, which, Jessup says, "we've been waiting for a long time.

"This is a drug that's already out there: not only is this [trial] potentially going to change the outcomes of patients with acute decompensated HF, but it will tell us what the safety is with particular respect to renal function."

Also in this session is EMPHASIS HF, looking at eplerenone in NYHA class 2 heart failure--as previously reported by heartwire , this trial was suspended before reaching its target enrollment after an interim analysis showed that those treated with the selective aldosterone inhibitor had a significant reduction in risk of the primary end point, cardiovascular death or HF hospitalization, compared with those on placebo. With full details now at AHA 2010, this trial "could change guidelines," Jessup said.

Finally, the ADVANCE trial of the HeartWare left ventricular assist device (VAD) is one that the advanced heart-failure community is very interested in, she said. "We are looking for a second nonpulsatile VAD, and surgeons in particular really like this VAD because it is implanted directly into the heart, rather than the pump itself being implanted in the abdominal cavity."

Late-Breakers: Monday and Tuesday

Monday's late-breaking sessions include two trials for which top-line results were released early by the companies: ROCKET AF, looking at rivaroxaban for stroke prevention in nonvalvular atrial fibrillation, and CLOSURE I, looking at PFO closure for prevention of stroke and transient ischemic attack (TIA). According to early results, ROCKET AF met its primary end point, whereas CLOSURE I did not. "We really want to know the details," Jessup said.

Also on Monday is theSMART AV trial, looking at how best to program CRTs, and a study looking at prescription omega-3-acid ethyl esters, P-OM3, to prevent recurrent atrial fibrillation.

For Tuesday, Jessup highlighted the ACT and GRAVITAS trials. ACT addresses the use of acetylcysteine for prevention of contrast-induced nephropathy in patients with reduced renal function--an agent Jessup notes is already commonly used. "This is the first real clinical trial to look at whether this is something that will actually reduce renal failure."

GRAVITAS, she notes, addresses two topics: "One, is it worth doing platelet-function testing? That's been in the news, and there's been a lot of [debate] as to whether we need to do this and whether it would have impact on outcomes. And two, if you see something based on platelet testing and you give a higher dose, is that going to have an effect? That's another piece of that puzzle."

Late-Breakers: Wednesday

Leading off the last day of late-breakers is an ASCOT analysis looking at baseline and on-treatment C-reactive protein (CRP) as both a target for treatment and a predictor of events. "We've heard so much about CRP in the past: this is really asking, if we know CRP at baseline and we use it as a target for treatment . . . is that going to change outcomes? And that's a critically important question that lots of people want the answer to. Also, how often do you need to measure it, and if it doesn't go down, what are you supposed to do? I suspect there will be huge discussion around this trial."

Another trial "people are excited about" is the SYMPLICITY HTN-2 trial, looking at endovascular ablation of the renal sympathetic nerves. "This is a fairly straightforward intervention that ideally would reduce the need for so many antihypertensives and lead to better compliance and better BP control," Jessup said. If it works, she said, "We will want to look at side effects, ease of ablation, and how many drugs the patients still need to take."

In Europe, she notes, renal-nerve ablation is primarily performed by interventionalists, although vascular surgeons are also interested. "If this turns out to be an interesting approach, I think it will also be interesting to see who grabs this," she said.

Finally, Jessup predicts the DEFINE trial of a new cholesteryl-ester-transfer-protein (CETP) inhibitor, anacetrapib, will also garner a lot of attention, coming as it does four years after the dramatic demise of the first drug in this class, torcetrapib. DEFINE, says Jessup, is "a pretty early trial, and of course everybody is looking to see whether this has a better safety profile than the CETP inhibitor in the past. . . . These are the primary results, so I expect we are going to hear more about this."

Beyond the Late-Breaking Clinical Trials

Jessup also pointed out that other late-breaking data will also be unveiled in what the AHA this year is calling "Clinical Science: Special Reports," which focus on new approaches to "systems of care."

"There are some really important things in here," she noted, including two big studies of telemonitoring for heart failure, one on emergency-department response times for AMI reperfusion, and one study looking at telephone-based approaches to improving hypertension care.

Other program highlights include:

  • This year's Nobel Laureate presentation--a joint lecture by Drs MichaelS Brownand Joseph LGoldstein.

  • The International Symposium, focused this year on cardiorenal syndrome.

  • Special sessions on the evolution of CPR, which celebrates its 50th anniversary this year.

  • An international luncheon honoring the 10 countries that had the most abstracts accepted.

This year's program is organized by seven multidisciplinary cardiovascular cores: cardiovascular imaging; epidemiology and prevention; genetics, genomics, and congenital CV disorders; heart-rhythm disorders and resuscitation science; myocardium function and failure; catheter-based and surgical interventions; and vascular disease biology and clinical science.

Each core will include topics tagged as clinical, basic, population, or translational science, and content will also be grouped by clinical "tracks."

According to Jessup, meeting organizers received almost 10 000 abstracts and accepted about 37%; roughly 50% of submissions came from outside the US.