Rehospitalization after intermittent levosimendan treatment in advanced heart failure patients: a meta‐analysis of randomized trials

Abstract

AimsIntermittent levosimendan administration has been suggested to improve survival in patients with advanced heart failure (AdHF). Quality of life is a key issue for AdHF patients and is negatively affected by frequent hospitalizations.Methods and resultsCENTRAL, Google Scholar, MEDLINE/PubMed, Scopus, and the Cochrane Central Register of clinical trials (updated 15/1/2017) were searched for randomized controlled trials investigating the effect of intermittent levosimendan administration in patients with AdHF. The primary outcome was the number of patients requiring rehospitalization 3 months after the end of treatment. A total of 319 patients from six trials were included. Overall pooled analysis showed that the use of levosimendan was associated with a significant reduction in the number of rehospitalizations at 3 months: 33/207 (16%) vs. 39/113 (35%), risk ratio 0.40, 95% confidence interval 0.27–0.59, P < 0.001, I 2 = 0%. This result was confirmed by sensitivity analyses.ConclusionsWithin the limitations of this meta‐analysis including also studies in which endpoints were not independently adjudicated and not clearly specified, repetitive or intermittent administration of levosimendan for patients with AdHF was associated with a reduction in the rehospitalization rate at 3 months. Large, high‐quality randomized controlled trials are needed to confirm this finding.

Repetitive levosimendan for a LION's heart?

“…The LION‐HEART data are in line with previous studies investigating the effect of repetitive administration of levosimendan and recent meta‐analyses, which demonstrated a reduction in hospitalization rate and mortality . Remarkably, LION‐HEART is the first multicentre trial in this field with positive results in both primary and secondary endpoints.…”

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge period

“…15,16 Individual studies, including the LevoREP trial, 17 were, however, underpowered to provide definite conclusions regarding these endpoints. 15,16 Individual studies, including the LevoREP trial, 17 were, however, underpowered to provide definite conclusions regarding these endpoints.…”

“…2,7 Strategies to prevent rehospitalizations during this vulnerable period have not been consistently successful so far, although adherence to well-established medical therapies at optimal doses is considered essential. [15][16][17] However, some of these studies were open-label, single-centre studies, and even the largest, double-blind trial performed to date-LevoRep (NCT01065194) 17 -was limited to 120 patients. Intermittent or continuous inotropic therapy has also been tested, but, despite favourable haemodynamic and symptomatic improvement in pilot trials, 11 no positive effect on hospitalizations has been observed, and, in fact, there has been a trend towards a higher mortality risk.…”

“…levosimendan have suggested that such a strategy may benefit patients with advanced HF by reducing hospitalization and mortality. [15][16][17] However, some of these studies were open-label, single-centre studies, and even the largest, double-blind trial performed to date-LevoRep (NCT01065194) 17 -was limited to 120 patients. Therefore, a larger study is needed to verify these favourable preliminary results.…”

Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology

“…Intermittent use of inodilators for long‐term symptomatic improvement or palliation has gained popularity, especially use of levosimendan, since the haemodynamic effect may last for >7 days after a 12–24 h infusion because of the pharmacologically active metabolite with a long half‐life . While meta‐analyses of several heterogeneous small trials of a repeated infusion strategy have suggested a positive effect on survival and a reduction in hospitalizations, such a survival effect has not been demonstrated in a single, adequately sized, prospective study. The LION‐HEART pilot study randomized 69 patients with advanced heart failure to placebo or levosimendan 0.2 µg/kg/min over 6 h every 2 weeks for 12 weeks .…”