New Orleans, LA - With 24 late-breaking clinical trials, 18 "smaller" late-breaking trials, and half a dozen additional "late-breaking" emerging-technology presentations, the American College of Cardiology (ACC) 2007 Scientific Sessions and concurrent i2 Summit will pose some tough challenges for people hoping to catch all of the clinical-trial results and still find time to eat, sleep, and schmooze. The i2 Summit begins Saturday, while the ACC main arena gets going on Sunday.

Some of the trial results, regardless of where the chips fall, will be "practice-changing," outgoing ACC president Dr Steven Nissen (Cleveland Clinic, OH) told heartwire.

One of the trials that has generated the most chatter in the run-up to the meeting is the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, to be presented by Dr William E Boden (University of Connecticut School of Medicine, Farmington). The trial, testing whether PCI plus intensive, guideline-driven medical therapy would be superior to intensive medical therapy alone, enrolled more than 2000 patients with documented myocardial ischemia and angiographically confirmed CAD. The composite primary end point is all-cause mortality or acute MI (time to first event) during a median five-year follow-up.

Nissen called COURAGE "a blockbuster either way."

"This will have a huge impact," he said. "About 40% of patients undergoing coronary interventions today are undergoing them for chronic stable angina. And the question is, how effective is intervention in comparison with just medical therapy alone in those patients?"

Likewise, Dr Salim Yusuf (McMaster University, Hamilton, ON), who will be a discussant following Boden's presentation, recently told heartwire, "If COURAGE shows a clear benefit of angioplasty, that's interesting, but if it shows no benefit compared with medical therapy, it's going to shake the foundation of interventional cardiology."

Earlier in the meeting, Dr Jean-Claude Tardif (Montreal Heart Institute, QC) is presenting results from another much-anticipated study, the Effect of Reconstituted HDL on Atherosclerosis (ERASE) trial. Nissen described ERASE as "a follow-on from the apo-A1 Milano story, which was very important. This is now wild-type, regular HDL, it's a larger study than the Apo-A1 study was, and it has the potential for commercialization more quickly because it's not a recombinant HDL, it's actually reconstituted from blood products. We will want to look at those results very carefully," he said.

Proving that in any story, the plot can be as important as the dénouement, several failed studies are also expected to capture ACC crowds. Three torcetrapib trials will be presented on Monday, hopefully providing some insights into the increased rates of deaths and CV events seen with the experimental HDL-raising drug. Pfizer halted the major study of its novel cholesteryl-ester-transfer-protein (CETP) inhibitor in December, as reported by heartwire.

"Even though we know the drug didn't work, it's so important to see the detailed results in terms of understanding mechanism and how the whole strategy of HDL raising will play out," Nissen said. "Many other pharmaceutical companies have drugs in the CETP-inhibitor class. So Wall Street is very interested and the companies are very interested, because the question we're going to be trying to answer through these imaging trials is whether this is a class effect or a molecular toxicity of torcetrapib alone."

Sponsors of two other clinical trials slated for presentation during the ACC late-breaking-trials session have released results in advance of the meeting, citing Securities and Exchange Commission regulations that require disclosure of any information that could have a major impact on stock price. As reported by heartwire, CV Therapeutics announced March 7, 2007 that its MERLIN TIMI-36 trial of ranolazine had failed to reach its primary end point. Today, AtheroGenics released preliminary results from its ARISE trial of AGI-1067, showing that the study had failed to reach its primary end point. For both ARISE and MERLIN, however, the companies—not surprisingly—are arguing that secondary-end-point and/or safety results that will be unveiled at the ACC meeting are compelling and suggest the drugs still have a future.

On the heart-failure front, Nissen singled out the EVEREST trial of tolvaptan, a vasopressin receptor antagonist being tested for its effects on clinical status, morbidity, and mortality in patients hospitalized with acute decompensated heart failure. While tolvaptan first showed promise in the phase 2 Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF) trial, the drug had no beneficial effects on LV remodeling and was not significantly different from placebo for the primary or secondary end points in the METEOR trial. Dr Marvin A Konstam (Tufts University, Boston, MA) is presenting the EVEREST results on Sunday.

Nissen also pointed to the Follow-Up Serial Infusions of Nesiritide for the Management of Patients With Heart Failure (FUSION II) trial. The study, a follow-up on FUSION I, is evaluating once- or twice-weekly treatment with nesiritide vs placebo as part of a posthospitalization treatment strategy in patients with end-stage heart failure. The primary end point for this study is mortality and cardio-renal rehospitalization; the study aims to determine whether the drug is safe for outpatient "tune-ups," a practice that was widely in use, off-label, before safety questions were first raised about the drug several years ago following its approval for use in an inpatient setting for patients with acute decompensated CHF.

"FUSION II could hit a home run, potentially," Nissen told heartwire. "I think it's an important trial."

In addition to COURAGE, several DES clinical-trial and registry results are slated for presentation during the i2 Summit.

"There's going to be a lot more information on stent thrombosis from DES, and there's going to be a lot of interesting new information on the merits of bypass surgery vs stenting vs medical therapy," i2 program chair Dr William Knopf (Atlanta Cardiology Group, GA) told heartwire. "Those will all be very exciting presentations."

The opening day of the i2 Summit will include nine-month clinical, angiographic, and IVUS results from the pivotal US SPIRIT-III Trial of Abbott's Xience V everolimus-eluting stent vs Boston Scientific's Taxus stent in more than 1300 patients and six-month angiographic and IVUS results from the ABSORB trial. ABSORB is a first-in-human, nonrandomized study of Abbott's fully bioabsorbable stent in 60 patients in Europe. Also on the first day of the meeting, Dr Michael Maeng (Aarhus University Hospital, Denmark) is presenting new registry data examining stent-thrombosis rates following DES implantation in western Denmark.

Knopf also highlighted presentations in the peripheral vascular arena, in particular "some interesting debates in carotid stenting vs carotid surgery, which is always a hot topic." Results from the 1500-patient EXACT carotid stenting registry is slated for presentation on Monday.