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      Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews

      systematic-review

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          Abstract

          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.

          Related collections

          Most cited references51

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          Declining Risk of Sudden Death in Heart Failure.

          Aldo P Maggioni, Milton Packer, Bertram Pitt … (2017)
          The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail.
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            Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients.

            Akshay S Desai, John J V McMurray, Milton Packer … (2015)
            The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death.
            Article 0 comments Cited 129 times – based on 0 reviews     Review now
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              Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials.

              S Yusuf, R Garg (1995)
              To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure. Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms. Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm. The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88; P < .001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74; P < .001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant. Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients.
              Article 0 comments Cited 114 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2018
                Publication date (Electronic): 28 July 2018
                Volume: 8
                Issue: 7
                Electronic Location Identifier: e021108
                Affiliations
                [1 ] departmentInstitute of Social and Preventive Medicine (IUMSP), Cochrane Switzerland , Lausanne University Hospital (CHUV) , Lausanne, Switzerland
                [2 ] departmentClinical Pharmacy Department , College of Pharmacy, King Saud University , Riyadh, Saudi Arabia
                [3 ] departmentLaboratoire de Biologie et Biométrie Evolutive-Equipe Modélisation des Effets Thérapeutiques , UMR 5558 Université Claude Bernard Lyon1 , Lyon, France
                Author notes
                [Correspondence to ] Dr Muaamar Al-Gobari; muaamar.algobari@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-1522-9812
                http://orcid.org/0000-0003-0571-7230
                Article
                Publisher ID: bmjopen-2017-021108
                DOI: 10.1136/bmjopen-2017-021108
                PMC ID: 6067373
                PubMed ID: 30056380
                SO-VID: 0b1330fe-2667-4805-8ff9-480d30667f9c
                Copyright © © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.
                License:

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 11 December 2017
                Date revision received : 12 June 2018
                Date accepted : 26 June 2018
                Funding
                Funded by: Département universitaire de médecine et santé communautaires (DUMSC);
                Funded by: The Federal Department of Economic Affairs, Education and Research (EAER), Switzerland;
                Categories
                Subject: Cardiovascular Medicine
                Subject: Research
                Subject: 1506
                Subject: 1683
                Custom metadata
                special-feature unlocked

                ScienceOpen disciplines: Medicine
                Keywords: cardiac failure,sudden death,umbrella review,meta-analysis,guidelines,treatment
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: cardiac failure, sudden death, umbrella review, meta-analysis, guidelines, treatment

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