Statins and risk of cardiovascular disease: Emulating a primary prevention trial in breast cancer survivors

BACKGROUND: Limited evidence is available from randomized trials to guide clinical decision-making for cardiovascular disease (CVD) prevention with statins among women with breast cancer. We leveraged real-world data to estimate the effect of statin therapy vs usual care on the 5-year risk of CVD among breast cancer survivors. METHODS: We sequentially emulated target trials using the National Cancer Institute-Kaiser Permanente Breast Cancer Survivors Cohort. Women aged 40 - 84 years, diagnosed with stage 0-III breast cancer from 1993 - 2022, without CVD, no statins in the past 6 months, and low-density lipoprotein cholesterol from 100 - 160 mg/dL were included. The outcome was CVD (ischemic heart disease, stroke, and cardiomyopathy/heart failure). We compared statin therapy to usual care (no statins unless indicated) in intention-to-treat and per-protocol analyses. RESULTS: Statin initiators were more likely to be older with a higher prevalence of cardiovascular comorbidities. In the intention-to-treat analysis, the 5-year risk difference was 0.3% (95%CI: -0.9,1.5), and risk ratio was 1.04 (95%CI: 0.86,1.25) for statin vs usual care. At 5 years, the proportion adherent to their initial strategy was 48% for statin and 24% for usual care. In the per-protocol analysis, the risk difference was -0.9% (95%CI: -2.9,2.2) and the risk ratio was 0.85 (95%CI: 0.51,1.36) for statin vs usual care. CONCLUSIONS: Our findings suggest that statin therapy may reduce the risk of CVD for breast cancer survivors, but the estimates are too imprecise for specific recommendations. Future research is needed to understand reasons for statin discontinuation, and opportunities to encourage adherence in this high-risk population.