Statin-related Adverse Drug Reactions in UK Primary Care Consultations: A Retrospective Cohort Study to Evaluate the Risk of Cardiovascular Events and All-cause Mortality

Aims: To investigate the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with statin-related adverse drug reaction (ADR) consultation in primary care and examine whether different treatments following the ADR affect subsequent outcomes.

Methods: This was a retrospective cohort study of statin users between 2004 and 2019 using IQVIA Medical Research Data (formally known as the THIN database). Patients with statin-related ADR consultation were matched by propensity score (1:1) to statin users without ADR consultation based on demographics, comorbidities and concomitant medication. Cox proportional hazard regression was used to compare the risk of subsequent CVD event and all-cause mortality, stratified by history of CVD. In the secondary analysis among patients with statin-related ADR, treatment changes within a 1-year period following the ADR were examined and the outcomes were compared between different treatment groups.

Results: Among 1 564 687 statin users, 19 035 (1.22%) had a statin-related ADR consultation in primary care. The mean (standard deviation) follow-up time was 6.32 (3.74) years and 5.31 (3.83) years for CVD primary and secondary prevention cohorts, respectively. Statin-related ADR consultation was associated with subsequent CVD events in both cohorts (adjusted hazard ratio [HR] of 1.39 [95% CI 1.23, 1.57] and 1.34 [95% CI 1.25,1.42], respectively). In the secondary analysis among patients with statin-related ADR consultation, we found that (i) continued statin prescription or combination of any statin with additional lipid-lowering treatment (LLT) and (ii) other LLT only were associated with lower risks of CVD event (adjusted HR 0.71 [95% CI 0.64, 0.78] and 0.75 [95% CI 0.62, 0.92], respectively) and all-cause mortality (adjusted HR 0.46 [95% CI 0.42, 0.50] and 0.52 [95% CI, 0.43, 0.64], respectively), compared to discontinuation of all LLT.

Conclusion: Statin-related ADR was associated with an increased risk of subsequent CVD event, indicating that these patients should be monitored more closely. Continued lipid-lowering medication is of importance to protect against CVD events and mortality.