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

Abstract

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.

Impact of ACEIs and ARBs-related adverse drug reaction on patients’ clinical outcomes: a cohort study in UK primary care

“…Previous studies have reported that ADRs related to other cardiovascular drugs increased the risk of adverse cardiovascular outcomes. 20 , 26 In addition, a study by Albani et al , which focused on patients with a history of acute coronary syndrome, showed that the intolerance to medications used for secondary CVD prevention, including ACEIs/ARBs, was independently associated with recurrent CVD events; 39 this is consistent with the findings of the study presented here. Schmidt et al showed that elevated creatinine levels of ≥30% following ACEI/ARB use were associated with CVD events, mortality, and end- stage renal diseases.…”

“…ACEI/ARB-related ADRs were observed in ∼1% of users of ACEIs/ARBs, which is a lower rate than that of previous studies (up to 3.9%); 13 , 14 this may be due to variability in ADR assessment and/or recording. 26 , 27 In addition, the severity of ADRs addressed in the consultations could not be identified, which might have affected the decision to continue or discontinue the medication. However, a previous systematic review estimated that the majority of ADRs in the primary care setting were of mild- to-moderate severity, compared with those requiring urgent medical care or hospitalisation.…”

“…The window period to examine treatment changes in the secondary analysis was adjusted from 12 to 6 months to evaluate robustness. 26 …”

“…UK primary databases have been previously used to investigate ADR-related consultations. 15,[25][26][27] The study protocol was approved by IMRD Scientific Review Committee (reference number:21SRC008).…”

“…ACEI/ARB-related ADRs consultation was defined using standardised designated codes, e.g., Read code chapter TJ (adverse drug reactions), as previously examined. 15,[25][26][27] This study used designated codes specific to ACEI/ARB-related ADRs consultation, thus it is estimated that the ADRs consultation is attributed to ACEI/ARB therapy. The index date was defined as the date of the first ACEI/ARB-related ADRs consultation (Supplementary Table 1).…”