麻豆传媒

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WASHINGTON -- Giving heart surgery patients the investigational calcium sensitizer levosimendan pre- and perioperatively did not reduce the risk for poor outcomes, researchers reported here.

Patients who received the drug prior to surgery were just as likely to experience heart attack, kidney failure, need for a mechanical assist device, or death as those in the control group, said , of the Duke Clinical Research Institute at Duke University in Durham, N.C., in a late-breaking clinical trials session at the American College of Cardiology (ACC) annual meeting. The study was simultaneously published online in the New England Journal of Medicine.

The placebo-controlled study recruited 882 patients with reduced ejection fraction (<35%) and evenly randomized them to "either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery."

There were two primary endpoints: a four-point composite of death or renal replacement therapy at 30 days, myocardial infarction at 5 days, or use of a mechanical assist device through day 5 and a two-point composite of 30-day mortality or use of a left ventricular assist device through day 5.

For the four-point composite endpoint, about one in four patients assigned to levosimendan reached it (105 of 428), as did 103 of the 421 control patients; thus there was clearly no benefit. Likewise, when considering just 30-day mortality and 5-day left ventricular assist device use, 56 levosimendan patients reached the endpoint as did 48 controls -- again no difference.

Drilling down to secondary outcomes, there were a few measurable differences: fewer patients in the active therapy group developed low-cardiac output syndrome -- 18.2% versus 25.7% of controls -- and the levosimendan patients were less likely to require inotropes.

During his ACC podium presentation, Alexander was clearly trying to make lemonade out of lemons as he summed up the negative trial this way: "Given its effect on cardiac output, low-cardiac output syndrome, and other inotrope use, and the absence of adverse safety signals, levosimendan is a reasonable option to consider in patients undergoing cardiac surgery where increased cardiac output is the desired objective."

But the trial was not designed as a safety study.

Alexander's colleague, also at Duke, admitted that the findings from the trial did not offer "really compelling evidence to use levosimendan. The trial was very neutral."

Nonetheless, Granger also sought to look on the bright side, adding, "But on the other hand, we need to use positive inotropic agents when patients have life-threatening hypoperfusion, and this trial then does provide some reassurance that levosimendan may be a safe, relatively safe, option for this population of patients. That's extrapolating the results some."