ORLANDO, FLA — An experimental drug for stabilizing irregular heart rhythms wasn’t more effective than placebo in preventing sudden cardiac death and unnecessary firings of implanted defibrillators, according to late-breaking research presented at the American Heart Association’s Scientific Sessions 2011.
The study is simultaneously published in Circulation: Journal of the American Heart Association.
“It’s somewhat disappointing because we thought we had something promising for a very serious problem,” said Peter R. Kowey, M.D., lead author of the study and chief of cardiology at Main Line Health, a Philadelphia-area hospital. “But we are very pleased with the quality of the data.”
Implantable cardioverter defibrillators (ICDs) can send electric shocks to the heart to normalize potentially fatal irregular heart rhythms that can cause the heart to stop effectively pumping blood.
Many patients also receive amiodarone or sotalol to prevent irregular rhythms, but the drugs aren’t always effective and can have side effects. No drug has gained regulatory approval in the United States for this particular indication. Celivarone is biochemically similar to amiodarone and another heart rhythm drug called dronedarone.
Kowey and his colleagues conducted the 486-patient ALPHEE trial after a smaller study of ICD patients called ICARIOS, completed in 2008, suggested celivarone might be beneficial. They successfully enrolled high-risk patients at 151 centers in 26 countries, including 133 patients at 37 U.S. sites. Patients were 64 years old on average.
The researchers found no meaningful differences among the high-risk patients randomized to placebo or 50, 100 or 300 mg daily doses of celivarone. A fifth group received amiodarone that was used as a “calibrator” to insure the integrity and interpretability of the trial.
Other findings included:
- No real differences in what triggered ICD responses occurred between the groups.
- Differences in patients with an appropriate ICD reaction weren’t significant.
- Six patients died of sudden death, but differences between the groups weren’t significant.
- Those on amiodarone showed a trend toward fewer unnecessary ICD shocks but a slightly higher death rate.
Some benefits of celivarone may have been lost because of the small number of participants in each study group. Women comprised only 11.3 percent and non-whites 7.2 percent, Kowey said.
“It is important for people to know about efforts to find the best therapy for ICD patients, even negative studies,” Kowey said. “We believe that publication of negative trials confirms the integrity of the process.”
The ALPHEE trial is formally named: Double Blind Placebo Controlled Dose Ranging Study of the Efficacy and Safety of Celivarone 50, 100 Or 300 Mg OD with Amiodarone as Calibrator for the Prevention of ICD Interventions or Death.
The ICARIOS trial was formally named: Double Blind Placebo Controlled Dose Ranging Study of the Efficacy and Safety of SSR149744c 100 or 300 mg for the Prevention of ventrICular ARrhythmia-Triggered Icd interventiOnS.
Co-authors are Etienne Aliot, M.D.; Alessandro Capucci, M.D.; Stuart J. Connolly, M.D.; Harry Crijns, M.D.; Stefan H. Hohnloser, M.D.; Piotr Kulakowski, M.D., Ph.D.; David Radzik, M.D.; and Denis Roy, M.D.
Disclosures are here: http://newsroom.heart.org/pr/aha/document/Disclosures_for_LBCT.xlsx.
Sanofi-Aventis funded the study.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding .
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