OBJECTIVES: To evaluate the effects of adherence and treatment intensity on cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD (diabetes), and stage 4-5 chronic kidney disease without CVD (CKD).

METHODS: This was a retrospective cohort study using the Clinical Practice Research Datalink. We included patients aged ≥18 years with hypercholesterolemia (≥2 statin and/or ezetimibe prescriptions) from 2010 to 2013. We followed them until death, myocardial infarction, unstable angina, ischemic stroke, heart failure, revascularization, or February 2016. Adherence was assessed annually using the proportion of days covered (PDC) with “adherent” defined as a PDC ≥80%. Treatment intensity was classified according to guidelines based on expected percent LDL-cholesterol reduction as low (<30% reduction), moderate (30%-50% reduction), or high (>50% reduction). Adherence and treatment intensity were multiplied to create a combined measure reflecting treatment intensity after accounting for adherence.

RESULTS: There were 16,701 CVD patients, 12,422 diabetes patients, and 674 CKD patients. In the CVD cohort, high intensity therapy patients were more likely to be adherent over time (84-72%) than low intensity (57-44%). The hazard ratio (HR) for adherent versus untreated patients was 0.65 (95% CI 0.60-0.70). The HR for high intensity versus untreated patients was 0.60 (95% CI 0.52-0.68). Using the combined measure, adherent patients receiving a high intensity regimen had a 34% lower cardiovascular event risk (HR: 0.66, 95% CI 0.56-0.78) than non-adherent patients receiving a low intensity regimen. The diabetic subgroup and the subgroup with multiple cardiovascular events had larger risk reductions. Diabetes and CKD cohort findings were similar.

CONCLUSIONS: Both high intensity and high adherence were associated with lower risk, and lower adherence and lower intensity were associated with higher risk. Patient education, improved adherence to treatment guidelines, and new therapeutic options that improve intensity and adherence should help to reduce cardiovascular risk.