(C-234) Nonacute Opioid Use and Cardiovascular Risk in Peri- and Post- Menopausal Women: An Observational Cohort Study

Background: This study quantified cardiovascular disease (CVD) risk associated with nonacute prescription opioid use, compared to non-use, in menopausal and postmenopausal women with chronic noncancer pain.

Methods: We emulated a sequence of target trials using 2010–2019 UK Clinical Practice Research Datalink data linked to hospital (HES) and mortality (ONS) records. Women aged 50–79 with newly diagnosed musculoskeletal conditions were followed for 1, 3, 6, 12, 24, and 36 months. Nonacute opioid therapy was defined as ≥2 prescriptions within 90 days for codeine, dihydrocodeine, tramadol, buprenorphine, morphine, oxycodone, fentanyl, or combination products (e.g., co-codamol). The primary outcome was incident composite CVD: stroke, myocardial infarction, heart failure, or venous thromboembolism (VTE). Weighted pooled logistic regression with high-dimensional propensity scores estimated hazard ratios (HRs) and 95% confidence intervals (CIs) in intention-to-treat (ITT) and per-protocol (PP) analyses. Sensitivity analyses assessed variation by age, condition, and individual CVD outcomes.

Results: Among 465,170 eligible women, composite CVD risk was highest within 1–3 months of opioid initiation. Adjusted HRs at 1 and 3 months were 1.40 (95% CI: 1.17–1.68) and 1.31 (1.13–1.52) [ITT], and 1.35 (1.06–1.71) and 1.30 (1.07–1.58) [PP]. Women under 65 had notably higher risk, with HRs of 1.66 (1.05–2.94) and 1.90 (1.20–3.02) at 1 and 3 months [PP]. VTE showed the highest individual risk, particularly in PP analyses: 1.61 (1.10–2.35) and 1.55 (1.12–2.15). CVD risk declined over time in the PP but remained stable in the ITT analysis.

Conclusion: Nonacute opioid therapy increases composite CVD risk within the first three months of initiation, with VTE posing the highest individual risk. Women under 65 showed heightened vulnerability. These findings underscore the need for cautious opioid prescribing and cardiovascular monitoring in menopausal women, particularly those under 65.