by Heartwire staff

March 27, 2008 (Chicago, IL) - This year's American College of Cardiology (ACC) 57th Annual Scientific Session and i2 Summit, combined for the first time with the Society for Cardiac Angiography and Interventions (SCAI) annual meeting, may set a new record for "late-breaking" presentations and pose a few problems for attendees with the intention of seeing them all. In total, there are 12 late-breaking trials in the main ACC program, 13 smaller "late-breaking abstracts," and a full 24 late-breaking interventional trials, with six presentations per day. On the final day of the meeting, the interventional and main meeting late-breakers overlap for one hour.

What's more, the eagerly awaited details from the controversial ENHANCE trial, barred as a late-breaker after the results were released earlier this year, will form part of a special session on Sunday at 11:30 AM..

ENHANCE data presented in full at ACC

Beginning just after noon on Sunday, principal investigator for ENHANCE Dr John Kastelein (Academic Medical Center, Amsterdam, the Netherlands) will present the full results in a special session moderated by ACC 2008 chair Dr Marc Shelton (Southern Illinois University, Springfield). Immediately following the presentation, an additional panel made up of Drs Harlan Krumholz (Yale University, New Haven, CT), Joseph Messer (Rush University, Chicago, IL), Rick Nishimura (Mayo Clinic, Rochester, MN), and Patrick O'Gara (Brigham and Women's, Boston, MA) will discuss the results.

"The discussion of the study is going to be pretty critical," Dr Steven Nissen (Cleveland Clinic, OH) told heartwire , adding that he knew the ACC had taken pains to select independent commentators. "That's very important, obviously, because the trial is so controversial."

ENHANCE has generated criticism and discussion since the publication of results in a press release two months ago. The study showed no benefit of the combination of ezetimibe and simvastatin, sold together as Vytorin by Merck/Schering-Plough Pharmaceuticals, over simvastatin alone. The study has been surrounded in controversy, with delays in publishing the findings raising questions from the House Committee on Energy and Commerce, as well as from Sen Charles Grassley (R-IA), the ranking member of the US Committee on Finance. Congress even sent the ACC and AHA letters questioning their funding from Big Pharma when they issued a press release urging patients not to overreact to the ENHANCE findings.

Dr Allen Taylor (Walter Reed Army Medical Center, Washington, DC) said the presentation is very important as an opportunity to finally see the data fully disclosed. "This includes not just the primary end point as disclosed in the media in January but also [an opportunity] to examine whether the findings were consistent across other end points and prespecified subgroup analyses," he told heartwire . "This will permit their full impact to be more adequately and fairly judged."

Media reports suggest that in the lead-up to Chicago, new prescriptions of Vytorin are still down. As published in the Wall Street Journal health blog, data from a research firm suggests that while Vytorin sales' reps are still a presence in doctor's offices, the share of new prescription sales written by these doctors is 6%, much less than the 14% share Vytorin had before the ENHANCE results were released in January [1]. Schering-Plough confirms that 2008 prescriptions for Vytorin and Zetia have declined since the ENHANCE results were released.

For the main ACC program, cardiologists who spoke with heartwire observed that while there are not a lot of blockbuster releases this year, there are several large-scale studies that should have an impact on practice.

Leading the pack is ON-TARGET, which enrolled more than 25 000 patients and is attempting to answer the question of whether the angiotensin receptor blocker (ARB) telmisartan combined with the ACE inhibitor ramipril is superior to ramipril alone in reducing the risk of CV death, MI, stroke, and hospitalization for congestive heart failure in high-risk subjects without heart failure (Monday, 10:00 AM, North Hall B1). Commenting on the anticipated importance of the ON-TARGET results, Nissen told heartwire : "The ARBs are being pushed very hard because the ACE inhibitors are mostly off-patent. So ARBs are the drugs now that are promoted, but not everybody is sure that they are as good. Another question the study will answer is what happens when you combine the two classes--do you get incremental benefits?"

Also singled out by cardiologists who spoke with heartwire were ACCOMPLISH and REVERSE. ACCOMPLISH is an 11 000-patient trial comparing CV outcomes in patients randomized to combination treatment with the ACE inhibitor benazepril and a diuretic or to benazepril and a calcium-channel blocker (CCB)--amlodipine. The trial was terminated early, although the reasons for termination will not be disclosed until the results are unveiled at the ACC. Interim data from the trial has been previously reported by heartwire (Monday, 10:15 AM, North Hall B1). The REVERSE trial is the first of several ongoing studies powered to show whether cardiac resynchronization therapy (CRT) on top of optimal medical therapy can improve one-year clinical outcomes in patients with NYHA class 1-2 systolic heart failure and a prolonged QRS interval. The study randomized 610 patients in North America and Europe. With the device therapy now limited to patients in NYHA class 3-4, a positive outcome in REVERSE, especially if confirmed by subsequent trials, could dramatically enlarge the population with an indication for CRT (Tuesday, 10:30 AM, North Hall B1).

Heart-failure trials test new drugs, and new doses

In the heart-failure arena, the randomized, open-label MOMENTUM trial, which had a projected enrollment of 200 patients, is testing the use of an investigational pump for assisted circulation in acute decompensated heart failure unresponsive to standard IV therapy. The twist, compared with conventional assisted circulation, is that the device moves blood in the descending aorta by about only one to one-and-a-half liters per minute. It enhances rather than replaces the natural circulation, according to one of the investigators, Dr William T Abraham (Ohio State University, Columbus). It's hoped that the augmented flow, by promoting flow-mediated vasodilation, will improve renal perfusion and "dampen down the neurohormonal axis," he told heartwire .

"It's really a neat study because it's not only looking at the effects of a pump per se, but it's looking at the effects of this physiology to see if the vicious cycle can be broken by it." (Tuesday, 1:45 PM, North Hall B1.)

Also among the Tuesday afternoon late-breaking trials are explorations of the adenosine-A1-receptor antagonist rolofylline (which has gone by the name KW-3902 in recent literature and heartwire coverage) and the sodium-potassium-ATPase inhibitor istaroxime in acute decompensated heart failure. The PROTECT pilot study of rolofylline sought to confirm earlier research suggesting the drug can enhance diuresis and thereby allow clinicians to pull back on administration of potentially renotoxic IV diuretics (Tuesday, 2:00 PM, North Hall B1).

"I think of acutely decompensated heart failure as being a sort of cardiorenal, neurohormonal, and hemodynamic storm, where everything is out of kilter, and you have to bring it back. But it's very complex. You can't treat just the hemodynamics without treating the kidneys, and you can't treat the kidney without treating the neurohormones. And so it really will take some exceptional agent or combination of agents to really add incremental value and improve outcomes. But we're starting to see some promise with some of these agents that are going to be discussed at the meeting," Abraham said.

Finally, the phase 2 HORIZON-HF study is looking at the effects of three different dosage levels of istaroxime on hemodynamics, neurohormones, and ventricular remodeling; the drug stands out among heart failure drugs for having positive inotropic effects and improving diastolic function (Tuesday, 2:15 PM, North Hall B1).

i2 Summit/SCAI program highlights

Despite the sheer number of interventional late-breakers and the high-profile involvement of the SCAI, cardiologists polled by heartwire said the line-up of interventional trials this year was not, in the words of one cardiologist, "particularly earthshaking," although much of it will be of interest to specialists in this field.

The four late-breaking interventional trial sessions have a different theme each day: PCI, AMI, DES, and "new frontiers." Interventionalists who spoke with heartwire identified several trials on day one (PCI) as "potentially important," in particular the 4500-patient ISAR-REACT 3 trial slated for presentation first thing on Saturday. The trial will hopefully answer the question of whether bivalirudin is superior to unfractionated heparin in troponin-negative patients who have been pretreated with 600 mg of clopidogrel. Later in this session, the stent analysis from the much-discussed TRITON-TIMI 38 will compare prasugrel with clopidogrel in ACS patients undergoing PCI (Saturday, 8:00 AM and 9:00 AM, Grand Ballroom S100).

AMI late-breaking clinical trials include longer follow-up data from the Massachusetts registry--first reported by heartwire at the American Heart Association meeting in 2007--comparing DES with bare-metal stents in AMI patients; two filter-protection/thrombus-aspiration trials; and results from the Canadian TRANSFER-AMI trial comparing a strategy of rapid transfer for PCI after fibrinolysis with fibrinolysis plus usual care (Sunday 8:00-9:30 AM, Grand Ballroom S100).

DES late-breakers include updates on the Xience stent, the Excel stent (with biodegradable polymer), the Conor stent (loaded for the first time with two different drugs in its novel "reservoir" design), and results from the MATRIX trial, examining duration of dual antiplatelet therapy after off-label DES use (Monday 8:00-9:30 AM, Grand Ballroom S100). Of the "new-frontiers" trials, experts who spoke with heartwire highlighted the one-year results from the EVEREST trial of the percutaneous MitraClip device to treat mitral regurgitation (Tuesday 10:30 AM, Grand Ballroom S100bc). Commenting on the i2/SCAI program during an ACC media preview, Dr David R Holmes (Mayo Clinic) observed: "One of the nice things about this meeting is the chance to interact between general cardiology and interventional cardiology. Most patients come to interventional cardiology through general cardiology, and so a meeting like this, which has a large number of general cardiologists . . . provides the chance to interact with the interventional cardiologists for problem-solving and discussing specific issues that everyone in cardiovascular disease faces."

Other news-generating drugs featured

Two glitazone trials are slated for presentation during the main ACC late-breaking trials/abstracts sessions, potentially offering insights into a field that was embroiled in controversy in 2007. PERISCOPE is comparing the impact of pioglitazone vs glimepiride on progression of coronary atherosclerosis, using intravascular ultrasound (IVUS), in patients with type 2 diabetes (Monday 11:00 AM, North Hall B1). The second study, a late-breaking abstract, is addressing the safety and efficacy of rosiglitazone in type 2 diabetics who have undergone CABG surgery (Tuesday 1:15 PM, North Hall B1).

Another drug that has both basked and burned in the limelight in recent years--rimonabant--will also be featured in a late-breaking session. The STRADIVARIUS trial is evaluating whether patients with abdominal obesity and coronary artery disease randomized to rimonabant instead of placebo show greater changes in atheroma volume at 18 months (Tuesday 10:00 AM, North Hall B1).

"Obviously, this is very interesting, because nobody has been able to show whether treating obesity has an impact on what happens in the coronaries; it's never been shown," Nissen commented to heartwire . "In fact, you really can't say to a patient, if you lose weight, your heart disease is going to be better. We just don't have the data."

  1. Rubenstein S. Vytorin languishes as cardiology meeting looms. Wall Street Journal health blog, March 19, 2008. Available at: http://www.wsj.com .

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