Objectives To summarise and synthesise the current evidence regarding the effectiveness of drug interventions to prevent sudden cardiac death (SCD) and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF).
Design Overview of systematic reviews.
Data sources MEDLINE, Embase, ISI Web of Science and Cochrane Library from inception to May 2017; manual search of references of included studies for potentially relevant reviews.
Eligibility criteria for study selection We reviewed the effectiveness of drug interventions for SCD and all-cause mortality prevention in patients with HFrEF. We included overviews, systematic reviews and meta-analyses of randomised controlled trials of beta-blockers, angiotensin-converting enzyme inhibitors (ACE-i), angiotensin receptor blockers (ARBs), antialdosterones or mineralocorticoid-receptor antagonists, amiodarone, other antiarrhythmic drugs, combined ARB/neprilysin inhibitors, statins and fish oil supplementation.
Review methods Two independent reviewers extracted data and assessed the methodological quality of the reviews and the quality of evidence for the primary studies for each drug intervention, using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) and Grading of Recommendations, Assessment, Development and Evaluation(GRADE), respectively.
Results We identified 41 reviews. Beta-blockers, antialdosterones and combined ARB/neprilysin inhibitors appeared effective to prevent SCD and all-cause mortality. ACE-i significantly reduced all-cause mortality but not SCD events. ARBs and statins were ineffective where antiarrhythmic drugs and omega-3 fatty acids had unclear evidence of effectiveness for prevention of SCD and all-cause mortality.
Conclusions This comprehensive overview of systematic reviews confirms that beta-blockers, antialdosterone agents and combined ARB/neprilysin inhibitors are effective on SCD prevention but not ACE-i or ARBs. In patients with high risk of SCD, an alternative therapeutic strategy should be explored in future research.
Systematic review registration PROSPERO 2017: CRD42017067442.
- cardiac failure
- sudden death
- umbrella review
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Contributors Design and conception: MA, FG and BB. MA is the guarantor. Project administration: BB. Writing original draft: MA. Critical analysis: all authors. Data curation: MA and SA. Statistical analysis: MA. Proofread and approved the final draft: all authors.
Funding MA, the corresponding author, received a financial grant (2014.0193) from The Federal Department of Economic Affairs, Education and Research (EAER), Switzerland, also from Département universitaire de médecine et santé communautaires (DUMSC), Lausanne university hospital (CHUV), Switzerland.
Disclaimer The former funders had no role in study design or conception, study analysis, writing or preparation of the manuscript.
Competing interests We declare that some authors of this overview are also authors of some of the included reviews. However, at least two reviewers systematically checked and validated the extracted data including study qualities. We declare that no other competing interests exist.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data are available in the manuscript and its supported files. Any more information can be requested from the corresponding author.