Association between nucleic acid COVID-19 vaccines and acute myocardial infarction in adults: a systematic review

Background: Post-marketing surveillance has documented cardiovascular adverse events following COVID-19 vaccination, including acute myocardial infarction (AMI); however, evidence regarding causal associations remains contradictory. Objective: To determine whether a causal association exists between nucleic acid-based COVID-19 vaccines (mRNA and DNA platforms) and AMI in adults aged 18-80 years. Methods: A systematic review following PRISMA 2020 guidelines searched PubMed, Cochrane CENTRAL, and Google Scholar for studies evaluating mRNA vaccines (Pfizer-BioNTech, Moderna) and DNA-based vaccines (AstraZeneca) with AMI as primary outcome. Quality assessment used the Newcastle-Ottawa Scale. Results: Twenty-nine studies from 16 countries were analyzed, including 14 population-based cohorts (>142.5 million individuals, >130,000 AMI cases), 12 case reports (54 AMI events), and three pharmacovigilance studies. Large cohorts demonstrated no significant association between nucleic acid vaccines and AMI. A Swedish study (8.1 million) showed protective effects (HR: 0.81; 95% CI: 0.74-0.89 for third dose). A Malaysian study (22.2 million) found no significant increase after BNT162b2 (dose 1 IRR: 0.97; dose 2 IRR: 1.08) or ChAdOx1 (dose 1 IRR: 1.02; dose 2 IRR: 1.58). Case reports documented temporal associations but had substantial methodological limitations. Quality assessment revealed low-to-moderate bias in population studies but high bias in case reports and pharmacovigilance data. Conclusions: High-quality population-based evidence from 14 independent cohorts does not support a causal association between nucleic acid-based COVID-19 vaccines and AMI. Case reports lack the methodological rigor to establish causality. The documented protective effects after booster doses and consistency across diverse populations demonstrate vaccine cardiovascular safety, supporting continued vaccination policies.