Duration of aromatase inhibitor use and long-term cardiovascular risk in breast cancer survivors

Abstract Background There are limited data on duration of aromatase inhibitor (AI) and cardiovascular disease (CVD) risk in breast cancer (BC) survivors. We examined risk of CVD and mortality associated with duration of AI use in postmenopausal women with early-stage hormone receptor-positive BC. Methods Postmenopausal women diagnosed with hormone receptor-positive BC (n = 5,853) who used an AI were included. Cause-specific hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between AI use duration (short-term: >0 and <2 years; intermediate-term: ≥2 and <5 years; long-term: ≥5 years) and CVD and mortality outcomes. The landmark method was used to avoid immortal time bias; the selected landmark was 6 years after BC diagnosis. Results Anastrozole was the AI predominantly prescribed (95.4%). Over a median follow-up of 3 years for women who survived 6 years after BC diagnosis, a lower risk of stroke was observed in intermediate-term AI users (HR = 0.60, 95% CI: 0.37-0.96) and long-term AI users (HR = 0.51, 95% CI: 0.30-0.85), than in short-term AI users. The longer duration of AI use was also associated with lower risk of all-cause mortality and non-CVD-related mortality. In addition, long-term AI users were at 37% lower risk of CVD-related mortality than short-term AI users. No significant differences were observed in risks of major adverse cardiovascular events, ischemic heart disease, and heart failure across the three groups. Conclusion Among postmenopausal women with early-stage hormone receptor-positive BC who survived to 6 years after BC diagnosis, longer duration of AI use was not associated with elevated CVD risk.