Effect of Levosimendan on the Short-Term Clinical Course of Patients With Acutely Decompensated Heart Failure

Abstract

In patients with ADHF, intravenous levosimendan provided rapid and durable symptomatic relief. As dosed in this trial, levosimendan was associated with an increased risk of adverse cardiovascular events. (Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure; NCT00048425).

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure

“…However, the larger SURVIVE14 and REVIVE15 trials were not confirmatory, and levosimendan is not licensed in the USA. Early enthusiasm led to rapid adoption in Europe, and although European guidelines do not give preference among different inotropes,2 in the Swedish Heart Failure Registry, levosimendan is the overwhelming inotropic agent of choice by cardiologists 21.…”

“…In early studies in ADHF, levosimendan improved haemodynamics and mortality compared with dobutamine12 and placebo 13. In later studies, it was not superior to dobutamine,14 and it improved symptoms but increased hypotension and arrhythmia compared with placebo 15…”

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study

“…Enrolling patients with normal‐to‐elevated blood pressure (SBP ≥125 mmHg) selects patients most likely to benefit from the vasodilatory properties of serelaxin and those less likely to suffer from the untoward effects of hypotension. Drug‐induced hypotension has been a major cause of failure in previous AHF trials 9, 26. Whether serelaxin could provide benefit to patients with lower blood pressures or initial evidence of compromised perfusion can be addressed in future clinical studies and clinical practice.…”

“…The clinical importance of WHF has been demonstrated in retrospective analyses of patient databases and intervention trials, as well as in a recent pooled analysis of 3691 patients from AHF trials 42. The occurrence of WHF is also sensitive to treatment as it may be reduced by drugs active on symptoms in the patients with AHF,9 and serelaxin treatment in RELAX‐AHF was associated with a 30% decrease in WHF within 14 days. Due to these encouraging results and the importance of this event to patients, RELAX‐AHF‐2 was designed from its initiation to include robust report forms and detailed documentation to appropriately collect and characterize WHF events, an endpoint elevated from exploratory in RELAX‐AHF to key secondary in RELAX‐AHF‐2 since the trial initiation.…”

“…In part due to the ageing of the population and more effective treatment of chronic heart failure (HF), its prevalence is expected to increase by 25% over the next 20 years 3 and the problem has expanded worldwide 4, 5. Patients hospitalized for HF have a 40–50% rate of HF exacerbation, of which 10–15% is in‐hospital worsening heart failure (WHF)6, 7, 8, 9, 10 and 30–40% is rehospitalization, within the first 6 months after discharge as well as a 10–15% mortality rate 11. Compared with ambulatory patients with stable chronic HF, patients hospitalized for AHF have a dramatic increase in their risk of death, similar or worse than that after a hospitalization for acute myocardial infarction or stroke 12.…”