Adherence to statins and risk of cardiovascular disease in patients with breast cancer.
Authors: Kwan Marilyn L. , Greenlee Heather , Iribarren Carlos , Rana Jamal S , Nguyen-Huynh Mai , Cheng Richard , Pimentel Noel , Laurent Cecile , Lee Valerie S. , Roh Janise M. , Rillamas-Sun Eileen , Hershman Dawn L. , Kushi Lawrence H. , Neugebauer Romain 
Published: June 2023

e24065 Background: Adherence to clinician prescribed cardiovascular disease (CVD) medications is poor in breast cancer (BC) survivors who are at heightened risk of CVD. Information on the effect of nonadherence to lipid-lowering medications on CVD risk in BC survivors is limited. We assessed adherence to statins, common lipid-lowering drugs, and their association with risk of CVD events in BC patients with dyslipidemia in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records (EHR). We identified 4,776 stage I-III BC patients diagnosed between 2005-2013 who were alive 6 months post-BC diagnosis (index date), and had a dyslipidemia diagnosis at the time of BC diagnosis along with ≥1 prior outpatient order or dispensing for a statin in the 30 months before index date. Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via EHR and validated diagnosis and procedure codes. Statin adherence was assessed using drug dispensing data and updated quarterly starting on the index date to calculate cumulative average adherence (CAA). Working marginal structural models (MSM) fitted with inverse probability weighting were used to evaluate the effect of statin adherence regimens on the hazards for each of the CVD events, while controlling for baseline and time-varying CVD clinical risk factors, BC tumor characteristics, cancer treatments, other lipid-lowering drugs, and socioeconomic status. We considered two MSM parameterizations for two CAA categorizations: poor CAA < 80% vs. good CAA≥80% (ref); and poor CAA < 80% vs. 80%≤good CAA < 100% vs. perfect CAA = 100% (ref). Results: Women were on average 67 years old with BMI of 30 kg/m2 and 65% non-Hispanic white. Over a mean follow-up of 6.5 years, 420 HF, 360 IHD, and 170 stroke events occurred. Overall, poor statin adherence was associated with higher risk of HF, IHD, and stroke combined: CAA < 80% (HR = 2.54; 95% CI: 1.09, 5.94) vs. CAA≥80%. Separately, compared with CAA≥80%, poor statin adherence was associated with a non-statistically significant higher risk of IHD alone, CAA < 80% (HR = 2.69; 95% CI: 0.85, 8.52) and stroke alone, CAA < 80% (HR = 8.13; 95% CI: 2.03, 32.51). Poor adherence was not associated with risk of HF alone, CAA < 80% (HR = 1.03; 95% CI: 0.31, 3.48) vs. CAA≥80%. When examining dose response of adherence, compared with perfect adherence (CAA≥100%), good adherence (80%≤CAA < 100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA < 80%) was associated with higher risk of any CVD event (HR = 2.45; 95% CI: 1.05, 5.70). Conclusions: Maintaining good adherence (at least 80%) to statins after BC treatment is overall beneficial for cardiovascular health in patients with dyslipidemia. However, unmeasured confounding cannot be ruled out in our study. Future studies should determine factors associated with lower adherence and ways to improve adherence.