Can a meta-analysis that mixes apples with oranges be used to demonstrate that levosimendan reduces mortality after coronary revascularization?

Abstract

We read with a great deal of interest the recently published meta-analysis of Maharaj and Metaxa [1] describ ing the eff ects of levosimendan on mortality after coronary revascularization. Th e authors concluded that levosimendan is able to reduce mortality in patients undergoing myocardial revascularization. Th eir conclu sion, however, is unreliable and misleading for several reasons. Th e basic reason is that their meta-analysis did not include comparable studies, thus violating the basic principle of meta-analysis. We believe that the inclusion in meta-analyses of studies so radically diff erent is a methodological bias: characteristics of patients, doses used and timing of drug administration were discordant enough to make a true meta-analysis impossible. What is missing is a critical analysis of individual studies: the authors have only tried to give a pooled estimate of eff ectiveness of levosimendan administration. As Green [2] points out about meta-analyses: ‘Metaanalysis should only be performed when the studies are similar with respect to population, outcome and intervention.’ Th e article of Moharaj and Metaxa does not follow these simple principles. We believe it is not correct to include in the same analysis studies where levosimendan is used for the treatment of postoperative cardiogenic shock and studies where it is used as ischemic preconditioning before cardiopulmonary bypass [3,4]. For example, the study of Tritapepe and colleagues [5] included in this meta-analysis describes the eff ects of a single low dose (24 mcg/kg) of levosimendan infused before cardiopulmonary bypass in patients under going surgical myocardial revascularization only for the assess ment of the possible preconditioning eff ect of the drug. Although we believe that levosimendan is an eff ective drug for the treatment of cardiogenic shock, we also believe this meta-analysis does not provide enough evidence that levosimendan can decrease mortality after myocardial revascularization.