(039) RAAS Inhibitors-Related Adverse Drug Reactions and the Risk of Subsequent Cardiovascular Event and All-Cause Mortality: A Cohort Study in UK Primary Care

Publication Number: 1035

Background: Renin-angiotensin-aldosterone system (RAAS) inhibitors users may develop adverse drug reactions (ADRs), such as cough, hypotension, hyperkalaemia, and angioedema. ADRs may affect patients' treatment outcomes unfavourably due to reduced medication adherence, interruption of the treatment, and limited therapeutic options. The risks associated with RAAS inhibitors-related ADRs have not been comprehensively examined.

Objectives: To investigate the risk of cardiovascular disease (CVD) events and all-cause mortality among patients with RAAS inhibitors-related ADRs consultation in primary care.

Methods: This propensity-score matched cohort study among the RAAS inhibitors users was conducted between 2004 and 2019 using data obtained from IQVIA Medical Research Data (formerly known as the THIN database). Patients with RAAS inhibitors-related ADRs consultation were matched (1:1) to RAAS inhibitors users without ADRs consultation. Cox proportional hazard regression model was used to compare the risk of CVD events (myocardial infarction and stroke/transient ischaemic attack) and all-cause mortality, stratified by CVD history and different indications for RAAS inhibitors. Treatment pattern changes within 1-year period following the ADRs were examined and the subsequent outcomes were then compared.

Results: Among 1,513,241 RAAS inhibitors users, 12,207 (0.83%) patients had RAAS inhibitors-related ADRs consultations. Mean follow-up period were 6.54 and 4.56 years for the CVD primary and secondary prevention cohorts, respectively. RAAS inhibitors-related ADRs were associated with subsequent CVD event and all-cause mortality in both primary (adjusted HR of 1.31, 95%CI 1.12, 1.53 and 1.12, 95%CI 1.00, 1.26, respectively) and secondary prevention cohorts (adjusted HR of 1.14, 95%CI 1.06, 1.23 and 1.17, 95%CI 1.11, 1.24, respectively). The results were consistent across different indications. In the secondary analysis, half (48.53%) of patients with ADRs continued to use RAAS therapy and these patients had a reduced risk of mortality (adjusted HR of 0.85, 95%CI 0.78, 0.93) compared to those discontinued RAAS therapy.

Conclusions: This study provides information on the burden of ADRs for patients and the health system. Patients with RAAS inhibitors-related ADRs had an increased risk of subsequent CVD events and all-cause mortality. The finding calls for additional monitoring and treatment strategies for patients affected with ADRs to mitigate the risks of adverse clinical outcomes.