JAMA reported on two important “negative” trials: The results of the EVEREST trial, comparing tolvaptan (a novel vasopressin V2 receptor blocker) to placebo for the treatment of acute CHF exacerbation, indicate that this agent had no effect on the primary endpoint of all-cause mortality or the composite endpoint of cardiovascular death, hospitalization for heart failure; secondary endpoints were also not effected. The TRIUMPH trial looked at the effect of tilarginine (an isoform-nonselective NOS inhibitor) in patients with MI and refractory cardiogenic shock and found no reduction in mortality rates in this patient-group. Enrollment was terminated early based on prespecified futility analysis.
An early release article available online published the results of a treatment intervention trial in patients with COPD: 449 patients with mod to severe COPD were randomized to one of three arms: tiotropium plus placebo; tiotropium plus salmeterol; or tiotropium plus fluticasone-salmeterol. Although the proportion of patients in each group who experienced an exacerbation of COPD did not differ, the last group demonstrated an improvement in lung function and disease-specific quality of life and reduced the number of hospitalizations for COPD exacerbation as well as all-cause hospitalizations as compared to the first group. Annals Link
2 Drugs discontinued:
The U.S. Food and Drug Administration (FDA) announced that manufacturers of pergolide drug products, which are used to treat Parkinson’s disease, will voluntarily remove these drugs from the market because of the risk of serious damage to patients’ heart valves. Two recent New England Journal of Medicine studies confirmed previous findings associating pergolide with increased chance of regurgitation of the mitral, tricuspid, and aortic valves of the heart. See: http://www.fda.gov/cder/drug/advisory/pergolide.htm
FDA also announced the withdrawal of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events associated with use of the drug. Novartis has agreed to voluntarily suspend marketing of the drug in the United States. The analysis included more than 11,600 patients treated with Zelnorm and over 7000 patients treated with placebo. The data showed that the risk of serious cardiovascular adverse events (e.g., angina, heart attacks, and strokes) associated with use of Zelnorm is higher than with placebo treatment. Thirteen Zelnorm-treated patients (or 0.1%) had confirmed cardiovascular ischemic events, and only 1 placebo-treated patient (or 0.01%) with an event. See: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01597.html
-Sean Cavanaugh, MD Associate Internal Medicine Residency Program Director