No benefits of statins for sudden cardiac death prevention in patients with heart failure and reduced ejection fraction: A meta-analysis of randomized controlled trials

PLoS One. 2017 Feb 6;12(2):e0171168. doi: 10.1371/journal.pone.0171168. eCollection 2017.

Abstract

Background and objectives: Statins showed mixed results in heart failure (HF) patients. The benefits in major HF outcomes, including all-cause mortality and sudden cardiac death (SCD), have always been discordant across systematic reviews and meta-analyses. We intended to systematically identify and appraise the available evidence that evaluated the effectiveness of statins in clinical outcomes for HF patients.

Design: Systematic review and meta-analysis.

Data sources: We searched, until April 28, 2016: Medline, Embase, ISI Web of Science and EBM reviews (Cochrane DSR, ACP journal club, DARE, CCTR, CMR, HTA, and NHSEED), checked clinicaltrials.gov for ongoing trials and manually searched references of included studies.

Eligibility criteria for selecting studies: We identified 24 randomized clinical trials that evaluated the efficacy of statins for HF patients. All randomized clinical trials were assessed for risk of bias and pooled together in a meta-analysis. Pre-specified outcomes were sudden cardiac death, all-cause mortality, and hospitalization for worsening heart failure.

Results: Statins did not reduce sudden cardiac death (SCD) events in HF patients [relative risk (RR) 0.92, 95% confidence interval (CI) 0.70 to 1.21], all-cause mortality [RR 0.88, 95% CI 0.75 to 1.02] but significantly reduced hospitalization for worsening heart failure (HWHF) although modestly [RR 0.79, 95% CI 0.66 to 0.94]. Nevertheless, estimated predictive intervals were insignificant in SCD, all-cause mortality and HWHF [RR, 0.54 to 1.63, 0.64 to 1.19, and 0.54 to 1.15], respectively. An important finding was the possible presence of publication bias, small-study effects and heterogeneity of the trials conducted in HF patients.

Conclusions: Statins do not reduce sudden cardiac death, all-cause mortality, but may slightly decrease hospitalization for worsening heart failure in HF patients. The evaluation of the risk of biases suggested moderate quality of the published results. Until new evidence is available, this study supports the 2013 ACCF/AHA guidelines to not systematically prescribe statins in "only" HF patients, which should help avoid unnecessary polypharmacy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cause of Death
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology*
  • Death, Sudden, Cardiac / prevention & control*
  • Heart Failure / complications*
  • Heart Failure / physiopathology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Odds Ratio
  • Publication Bias
  • Randomized Controlled Trials as Topic
  • Stroke Volume*
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Grants and funding

MA, the corresponding author, received a financial grant (2014.0193) from The Federal Department of Economic Affairs, Education and Research (EAER), Switzerland. HHL received a financial grant from University Claude Bernard Lyon 1 (scholarship of French Ministry of Higher Education & Research) for a three-year PhD contract (10/2014-09/2017) at the UMR 5558 CNRS. All funding is independent from the study design, data interpretation, writing or the decision to submit the article for publication.