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

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.

Fig 1. Flow chart for search result.

Fig 2. Risk of bias for included studies.

A) Risk of bias graph for statin trials in heart failure patients: review authors' judgments about each risk of bias item presented as percentages across all included studies. B) Risk of bias summary for statins in heart failure patients: review authors' judgments about each risk of bias item for each included study.

Fig 3. GRADE summary of findings table.

Fig 4

Efficacy of statins compared with control in heart failure for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF).

Fig 5

Efficacy of statins compared with control in heart failure stratified by follow-up duration for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF).

Fig 6. Sensitivity analysis without corona and GISSI-HF.

Fig 7. Sensitivity analysis without less powered studies.

Fig 8

Efficacy of statins compared with control in heart failure stratified by sample size (more than 100 or less than 100) for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF).

Fig 9

Efficacy of statins compared with control in heart failure stratified by population type (ischaemic or non-ischaemic) for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF).

Fig 10

Efficacy of statins compared with control in heart failure stratified by endpoint (those with against without mortality and/or HWHF) for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF). [Random-effects model].

Fig 11

Funnel plots of SE (log odds ratio) by odds ratio to evaluate publication bias for the effect of treatment for prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF). (Fixed-effects model).

Fig 12

Efficacy of statins compared with control in heart failure stratified by statin type (lipophilic versus hydrophilic) for the prevention of (A) sudden cardiac death (SCD) (B) all-cause mortality, and (C) hospitalization for worsening heart failure (HWHF).