Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice

Abstract

Abstract:Levosimendan is a calcium sensitizer and adenosine triphosphate–dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.

Postoperative management of patients undergoing cardiac surgery in Austria

“…Shortly after this survey three major trials [19–21] put the expected effect of levosimendan in cardiac surgery into perspective, which prompted a more conservative expert consensus regarding its use in this context [22]. This may have changed the centers’ attitude towards use of this inotrope.…”

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

“…Levosimendan has been studied in more than 40 clinical trials in cardiac [119][120][121][122] Expert advice derived from these new data is that "levosimendan cannot be at the moment recommended for routine use in all cardiac surgery settings". 122 However, there appears to be potential for significant mortality benefit in some subgroups of patients, such as those with low ejection fraction or those undergoing isolated coronary artery bypass grafting (CABG) procedures.…”

“…A recalculation incorporating data from three recent large RCTs (Levosimendan in Coronary Artery Revascularisation [LICORN], Levosimendan to Reduce Mortality in High Risk Cardiac Surgery Patients [CHEETAH] and LEVO-CTS) causes dilution of the effect size of that estimate. [ 119 – 122 ] Expert advice derived from these new data is that “levosimendan cannot be at the moment recommended for routine use in all cardiac surgery settings”. [ 122 ] However, there appears to be potential for significant mortality benefit in some subgroups of patients, such as those with low ejection fraction or those undergoing isolated coronary artery bypass grafting (CABG) procedures.…”

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

“…A recalculation incorporating data from 3 recent large RCTs [Levosimendan in Coronary Artery Revascularisation (LICORN), Levosimendan to Reduce Mortality in High Risk Cardiac Surgery Patients (CHEETAH), and LEVO-CTS] causes dilution of the effect size of that estimate. 119 – 122 Expert advice derived from these new data is that “levosimendan cannot be at the moment recommended for routine use in all cardiac surgery settings.” 122 However, there appears to be potential for significant mortality benefit in some subgroups of patients, such as those with low ejection fraction or those undergoing isolated coronary artery bypass grafting (CABG) procedures. 123 , 124 Whether these findings may be interpreted as a lack of efficacy of levosimendan in patients undergoing valve surgery due to differences in the underlying pathophysiology or dosing, or as a result of procedure-specific differences in surgical and perfusion management (ie, too low a dose applied before cardiopulmonary bypass or use of crystalloid cardioplegia solutions) needs to be addressed in future studies.…”