Vytorin study steals show at American College of Cardiology meeting

May 12, 2008

The American College of Cardiology meeting spotlights ENHANCE study on Vytorin

Even prior to the recent American College of Cardiology (ACC) annual meeting, held in Chicago, previews of the data from the ENHANCE trial had already attracted intense media attention. This was largely because of unexpectedly disappointing results and a congressional investigation into delays in data presentation.

Representing a panel appointed to discuss ENHANCE results, Harlan M. Krumholz, M.D., professor of medicine at Yale University, commented: "For clinicians who may have employed this medication [i.e., EZE] before exhausting the options with statins, the strongest recommendation we can make on this panel is, 'Turn back to statins, especially those with favorable outcomes data.'"

Outcomes data for Vytorin, considered to be the true test of efficacy (as opposed to the surrogate endpoint of ENHANCE), are expected in 2012 with results of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial), a trial comparing EZE/SMV with SMV alone among 18,000 patients recovering from acute coronary syndromes.

In other news from the meeting, researchers reported that when orthopedic issues or age preclude active exercise testing, adenosine is widely used as a vasodilating stressor in myocardial perfusion imaging (MPI) evaluations (SPECT) of heart disease. Adenosine has the drawback, however, of producing flushing, chest pain, shortness of breath, nausea, and atrio-ventricular block (AVB) in up to 80% of patients, stated James E. Udelson, M.D., Tufts-New England Medical Center, Boston. Also, adenosine requires a cumbersome six-minute pump infusion.

Udelson presented what he described as "...significant practice-changing results for binodenoson (BINO), a selective adenosine A2A receptor agonist delivered in a 30-second bolus. BINO was tested in two Phase III trials (VISION 302/VISION 305) among 852 patients referred generally for chest pain to pharmacologic stress MPI. Investigators wished to see if BINO and adenosine detected similar magnitudes of ischemia in the same patients, and compared side effects, particularly second- or third-degree AV block. Patient preference was also evaluated.

Udelson reported that no second- or third-degree AV block occurred with BINO. AV block, flushing, chest pain, and dyspnea were all reported at significantly higher rates with adenosine. No side effects were significantly greater with BINO than with adenosine. About 70% of patients preferred BINO. Udelson said, "BINO provides similar clinical information as adenosine, but is associated with a significant reduction in the incidence and intensity of many side effects."

The ISAR REACT3 (Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment) trial compared unfractionated heparin (UFH) and bivalirudin (Angiomax, The Medicines Co.) among 4,570 patients (mean age 67 years, 76.5% male, 80% with multivessel disease) undergoing PCIs (percutaneous coronary interventions). All patients were biomarker- (troponin T and CK-MB) negative with stable or unstable angina and had been treated with aspirin >325 mg and clopidogrel 600 mg for ≥ two hours before the procedure. "The hypothesis," stated Adnan Kastrati, M.D., Deutsches Herzzentrum, Munich, Germany, "is that bivalirudin is superior to UFH for biomarker-negative patients undergoing PCI after optimal pretreatment with clopidogrel."