Left ventricular dysfunction following cardiac surgery remains a significant perioperative challenge, one often treated with inotropic support, however practice patterns vary widely and there are few outcome data to support a standardized practice. Levosimendan represents a newer class of “inodilators”, calcium sensitizers, thought to improve cardiac output without increasing myocardial oxygen consumption.
In the Levosimendan to Reduce Mortality in High Risk Cardiac Surgery Patients (CHEETAH) randomized trial, 506 patients with a preoperative ejection fraction < 25%, a preoperative need for intraaortic balloon pump (IABP) support, or post-operative need for support with IABP or high-dose inotropes within 24 hours of cardiopulmonary bypass were randomized 1:1 to receive either levosimendan infusion or placebo plus standard medical therapy in a double-blinded fashion.
The primary outcome of the study was 30-day mortality. No difference in the primary outcome was found between the levosimendan group (12.9% mortality) and the placebo group (12.8% mortality) (ARR 0.1%, CI -5.7-5.9, P 0.97), leading to early interruption of the trial for futility. There were also no significant differences in secondary outcomes or adverse events.
Notably the mean levosimendan dose was 0.066 +/- 0.031 mcg/kg/min, lower than all previous trials which used at least 0.1 mcg/kg/min.
This study challenges prior trials and meta-analyses suggesting a higher rate of survival with levosimendan. Though lower doses of the study drug were employed in this trial, leaving open the door for further study on dose-response relationships, these data clearly represent a setback when it comes to management of higher-risk cardiovascular surgery patients.
Landoni G, Lomivorotov VV, Alvora G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2021-2031.
Tara Jones, MD PharmD and James M. McCabe, MD
University of Washington, Seattle, USA