What are potential ideas for meta-analysis in cardiology?

Potential Meta-Analysis Topics in Cardiology

High-Priority Areas with Existing Evidence Gaps

Antiplatelet Therapy Optimization

Dual antiplatelet therapy duration after drug-eluting stent placement remains incompletely defined, particularly in specific subgroups. 1 A meta-analysis comparing optimal duration (1 year vs. extended therapy beyond 1 year) stratified by bleeding risk, diabetes status, and complexity of coronary disease would address current clinical equipoise. 1

• Clopidogrel versus aspirin monotherapy for long-term secondary prevention represents an emerging area, with recent individual patient data suggesting superiority of clopidogrel for major adverse cardiovascular events without increased bleeding. 2 A comprehensive meta-analysis incorporating real-world data alongside randomized trials could definitively establish optimal antiplatelet choice.

• Antiplatelet therapy in systemic left ventricular dysfunction without atrial fibrillation shows conflicting evidence, with the WARCEF trial demonstrating nonsignificant trends. 1 Pooling data across trials examining aspirin alone, dual antiplatelet therapy, and vitamin K antagonists could clarify optimal antithrombotic strategy in this population.

Novel Oral Anticoagulants in Special Populations

Direct oral anticoagulants (DOACs) demonstrate favorable risk-benefit profiles compared to warfarin in atrial fibrillation, but subgroup analyses reveal important heterogeneity. 3, 4 Meta-analyses are needed for:

• DOACs in atrial fibrillation patients with heart failure and reduced ejection fraction (<40%), as existing data show no interaction between heart failure status and DOAC efficacy, but mortality differences persist. 5 A focused analysis on heart failure severity (NYHA class III-IV vs. I-II) and ejection fraction strata would inform clinical decision-making.

• DOAC dosing strategies based on time in therapeutic range (TTR) with warfarin, given that relative bleeding reduction with DOACs is greater when center-based TTR is <66% versus ≥66%. 3 This could identify populations where DOACs provide maximal benefit over well-managed warfarin therapy.

• Comparative effectiveness of individual DOACs using network meta-analysis with updated real-world data, as indirect comparisons show apixaban may have superior bleeding profiles compared to rivaroxaban and dabigatran 150 mg. 3, 4, 6

Revascularization Versus Medical Therapy in Stable Ischemic Heart Disease

The optimal management strategy for stable ischemic heart disease with moderate-to-severe ischemia remains controversial, with 16 published meta-analyses reaching contradictory conclusions. 1 A definitive meta-analysis is needed that:

• Includes only contemporary trials (post-2010) to reflect modern guideline-directed medical therapy and current-generation drug-eluting stents, as older studies have questionable relevance to current practice. 1

• Stratifies by quantitative ischemia burden (10-15% vs. >15% myocardium) and anatomic complexity (SYNTAX score), as outcomes may vary substantially based on these factors despite current data limitations. 1

• Analyzes per-protocol populations separately from intention-to-treat, given that crossover rates in strategy trials reduce power to detect differences, and per-protocol STICH analysis showed mortality benefit with CABG. 1

• Incorporates quality-of-life outcomes as co-primary endpoints alongside mortality and myocardial infarction, as the incremental benefit of revascularization on symptoms versus medical therapy alone remains debated. 1

Cardiac Risk Stratification in Cerebrovascular Disease

Patients with acute ischemic stroke have 2-5% short-term cardiac mortality, but optimal cardiac evaluation strategies are undefined. 1 A meta-analysis examining:

• Timing and intensity of cardiac screening (troponin surveillance, echocardiography, stress testing) in stroke patients without known coronary disease could identify cost-effective approaches to detect high-risk cardiac disease.

• Cardiac outcomes stratified by stroke mechanism (large-vessel atherosclerosis vs. small-vessel disease vs. cryptogenic), as cardiac event rates likely vary substantially by etiology despite limited current data. 1

Neurohormonal Antagonism in Heart Failure with Mildly Reduced Ejection Fraction

Heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) represents a heterogeneous population with conflicting evidence for guideline-directed medical therapy. 1 Meta-analyses are needed for:

• ACE inhibitors/ARBs/ARNIs in HFmrEF, as post-hoc analyses from CHARM and PARAGON-HF suggest benefit in lower LVEF ranges (41-49%), but data remain limited and hypothesis-generating. 1

• Mineralocorticoid receptor antagonists in HFmrEF, given that TOPCAT subgroup analysis (LVEF 44-49%) showed benefit primarily in Americas cohort, suggesting regional differences or data quality issues. 1

• Beta-blockers in HFmrEF with sinus rhythm, as the BB-meta-HF analysis included only 575 patients with LVEF 40-49%, insufficient to definitively establish benefit. 1

Systemic Right Ventricle Medical Management

Neurohormonal antagonism in systemic right ventricular dysfunction shows no benefit in existing small trials, but meta-analysis could detect modest effects. 1 A comprehensive analysis including:

• ACE inhibitors, ARBs, and aldosterone antagonists pooled together as a class effect, given individual trials were underpowered (largest trial enrolled only 88 of planned 102 patients). 1

• Stratification by underlying diagnosis (D-transposition of great arteries post-atrial switch vs. congenitally corrected transposition vs. other), as pathophysiology and response to therapy may differ. 1

Methodological Considerations for Future Meta-Analyses

Meta-analyses in cardiology frequently reach opposite conclusions due to study selection criteria, particularly regarding inclusion of patients with recent myocardial infarction. 1 Future analyses should:

• Obtain individual patient-level data rather than relying on published aggregate data, as this allows adjusted comparisons and subgroup analyses not possible with study-level meta-analysis. 1

• Standardize endpoint definitions, particularly for periprocedural myocardial infarction, which varies substantially across trials and affects comparative effectiveness estimates. 1

• Account for temporal trends in background medical therapy and procedural techniques, as studies performed over several decades may not reflect contemporary practice patterns. 1

• Pre-specify subgroup analyses based on clinically relevant patient characteristics (diabetes, chronic kidney disease, prior myocardial infarction) and disease severity markers (ischemia burden, anatomic complexity, ventricular function). 1, 3