Introduction: Long term cardiovascular toxicity of cancer treatments is increasingly recognized, however, data on the effect of statins on CVD prevention among breast cancer survivors are limited. We extended inferences about the effects of statins on the 5-year risk of CVD from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid Lowering Trial (ALLHAT-LLT) to a population of breast cancer survivors.

Methods: We included data from ALLHAT-LLT, which randomized moderately hypercholesterolemic and hypertensive adults aged 55−84 years to pravastatin (use of statins unless contraindicated) or usual care (no use of statins unless indicated), and the National Cancer Institute-Kaiser Permanente Breast Cancer Survivors Cohort, in which we emulated a single arm target trial of usual care among women with non-metastatic breast cancer aged 40−84 years. We estimated intention-to-treat and per-protocol effects among breast cancer survivors using assumptions of partial treatment exchangeability in the target population and transportability of conditional relative effect measures. The outcome was CVD (fatal and non-fatal in-patient myocardial infarction, stroke, heart failure).

Results: There were 9,611 ALLHAT-LLT participants (mean age 66) and 7,602 breast cancer survivors (mean age 65). In intention-to-treat analyses, the estimated 5-year risk difference of CVD comparing pravastatin and usual care was -0.2% (95% confidence interval -2.3%,2.3%) in ALLHAT-LLT and -0.3% (-1.4%,1.0%) among breast cancer survivors. In per-protocol analyses, the estimated 5-year risk difference was -3.1% (-6.3%,-0.1%) in ALLHAT-LLT and -1.7% (-3.3%,-0.01%) among breast cancer survivors.

Conclusions: Adherence to, but not assignment of, pravastatin compared to usual care led to reductions in CVD risk among ALLHAT-LLT participants and breast cancer survivors. Statins may help reduce CVD risk among breast cancer survivors receiving potentially cardiotoxic cancer treatments.