Association between chronic opioid exposure and cardiovascular disease: a systematic review and meta-analysis

Chronic opioid exposure (COE) is linked to adverse health outcomes, but its relationship with cardiovascular disease (CVD) remains unclear. This systematic review and meta-analysis aimed to summarise published evidence on CVD risk associated with COE, including prescription opioids, opium use, and opioid use disorder (OUD).

Following PRISMA guidelines and PROSPERO registration (CRD42024573206), we searched multiple databases for relevant human studies reporting associations between COE and CVD. Random-effects meta-analysis estimated pooled odds ratios (OR) with 95% confidence intervals. Subgroup analyses and meta-regression explored associations by COE type, CVD outcome, and potential moderators. Risk of bias was assessed using ROBINS-E.

Seventeen studies (1,676,000 participants) met inclusion criteria, with 13 studies contributing 22 effect sizes to meta-analysis. COE was associated with increased CVD risk (pooled OR: 1.74, 95% CI: 1.12-2.70), though substantial heterogeneity was observed. Cerebrovascular accidents (OR: 1.84, 95% CI: 1.45-2.35) and ischaemic heart disease (OR: 1.51, 95% CI: 1.40-1.63) showed the strongest associations. Opium use had a significant association with CVD, while findings for OUD and prescription opioids were less consistent. Meta-regression identified study design as a key moderator.

COE is associated with increased risk of CVD, particularly cerebrovascular accidents and ischaemic heart disease. Given the global opioid and CVD burden, targeted interventions and integrated care approaches are needed. Findings are limited by heterogeneity and risk of bias in published studies. Further high-quality research should explore pathophysiological mechanisms, causality, dose-response relationships, and the potential reversibility of CVD risk following opioid cessation.