A recent clinical trial investigated the use of Levosimendan (a drug used for the management of congestive heart failure) for reducing mortality rates amongst patients with perioperative heart dysfunction, a major complication associated with heart surgery. Previous small trials have suggested this therapeutic may result in a high rate of survival for patients undergoing heart surgery.
More than 1 million patients annually undergo heart surgery in the United States and Europe alone. A major complication that contributes to mortality and affects approximately 20% of patients is acute perioperative (which includes the three phases of surgery; preoperative, intraoperative and postoperative) left ventricular dysfunction. Left ventricular dysfunction (LVD) and subsequent congestive heart failure is the end result of a number of heart disorders. Typically, the left ventricle (heart chamber) is damaged, resulting in trouble pumping blood through the aorta and to the body.
Previous small trials have suggested that levosimendan could potentially be used for hemodynamic (blood flow around the body) support. Levosimendan is an inotropic agent that affects muscle contraction in the heart. It has also been shown to be cardioprotective, antioxidant and anti-inflammatory, properties thought to protect patients undergoing heart surgery.
The results of the multicentre (14 centers in Italy, Russia and Brazil), randomized, double-blind, placebo-controlled trial by Landoni and colleagues were published recently in the New England Journal of Medicine. The trial included 506 patients, of which 248 patients were randomly assigned to receive levosimendan and 258 to receive placebo.
The patients involved in the trial were selected based upon their need for perioperative blood flow support after heart surgery. Patients were excluded if they had previously shown an adverse reaction to levosimendan, were included in another trial, had received a kidney or liver transplant or the presence of a do-not-resuscitate order.
After 30 days, no significant difference was observed between groups, with the death of 32 (12.9%) patients in the levosimendan group and 33 (12.8%) in the placebo group. In addition, there was no significant difference in the causes of death between the two groups, nor was there any difference in the incidence of secondary outcomes such as hypertension or arrhythmias.
This trial differed from previous investigations which looked at the use of levosimendan in coronary-artery bypass grafting. Increasing the dose may have been effective in reducing mortality but it is not known if a higher dose would increase the risk of secondary outcomes.
These findings do not support administration of levosimendan, in addition to standard care, to reduce mortality rates after heart surgery in patients requiring perioperative hemodynamic support.
Written By: Lacey Hizartzidis, PhD