Cardiovascular disease remains a leading cause of death globally, with coronary artery disease the most prevalent form. Among survivors of acute myocardial infarction (MI), sudden cardiac death (SCD) is a major and often fatal complication, accounting for the largest proportion of deaths in this population. Implantable cardioverter-defibrillators (ICDs) are widely used as a strategy for primary prevention of SCD. However, available studies differ substantially in design and reporting, producing heterogeneous evidence about the magnitude and consistency of benefit after MI.
Key uncertainties in the literature include the optimal timing for ICD implantation after MI, the approaches used for risk stratification when selecting patients for prophylactic ICDs, and inconsistent reporting of non-rhythmic causes of death following ICD implantation. These issues complicate interpretation of trial results and limit clear clinical recommendations.
This protocol describes a systematic review and meta-analysis that will pool randomised controlled trials (RCTs) comparing prophylactic transvenous ICD (TV-ICD) implantation to other medical therapies for the primary prevention of SCD after MI. The review will follow established evidence-synthesis and reporting standards and will be conducted according to a predefined analysis plan.
A comprehensive literature search will be performed across multiple electronic databases: Scopus, Ovid MEDLINE, EMBASE (Ovid Platform), Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, ProQuest (Health and Medicine), and CINAHL (EBSCO). The search timeframe spans January 1980 through June 2025. The search will be restricted to peer-reviewed original studies conducted in human subjects and published in English.
Study design eligibility is limited to randomised controlled trials that examine prophylactic TV-ICD implantation for primary prevention of SCD in patients who previously experienced MI. Details such as participant characteristics, timing of implantation relative to MI, comparator medical therapies, and outcome ascertainment will be extracted when reported in the source trials.
The primary outcome for this review is all-cause mortality. Effect measures for the primary outcome will be reported using Hazard Ratios (HRs) with 95% confidence intervals, where available from included trials. Secondary outcomes and additional endpoints are not specified in the protocol summary; any further reported outcomes will be described and synthesized according to the available trial data.
Pooled effect sizes will be estimated using a random-effects model to account for between-study variation. Analysis will adhere to a structured and predetermined statistical plan. Where trials report time-to-event outcomes, HRs will be used as the principal measure of effect. Heterogeneity across studies will be assessed and reported, and sensitivity analyses may be applied based on study quality and other design features.
Based on data availability from included RCTs, subgroup analyses will be performed. Prespecified subgroup categories are not detailed in the protocol summary; however, the review will employ subgroup and sensitivity approaches to explore sources of heterogeneity such as timing of ICD implantation after MI, different patient risk profiles, and variations in comparator medical therapy.
The systematic review and meta-analysis aim to provide primary evidence regarding the effectiveness of prophylactic TV-ICD implantation on all-cause mortality in patients after MI, with the goal of informing primary prevention of SCD. Demonstrating benefit could influence strategies to reduce the community incidence of out-of-hospital cardiac arrests, potentially improving survival and post-MI quality of life. The protocol notes that out-of-hospital cardiac arrests currently have a survival rate of less than 10% and that survivors may incur long-term neurological damage.
This review protocol is registered on PROSPERO (CRD42023456995). The systematic review and meta-analysis will be developed according to the Joanna Briggs Institute Manual for Evidence Synthesis (2024 edition) and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.
The protocol acknowledges heterogeneity across existing trials as a major limitation in the evidence base. Specific contributors to heterogeneity include variability in the timing of ICD implantation after MI, differences in risk stratification methods used to select patients for ICDs, and inconsistent reporting of non-rhythmic causes of death post-implantation. Where trial reports lack detail, the protocol specifies that data extraction and analyses will be limited to reported information.