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

BACKGROUND: Adverse drug reaction (ADR) related to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may negatively affect patients' treatment outcomes. AIM: To investigate the impact of ACEIs/ARBs-related ADR consultation on cardiovascular disease (CVD) events and all-cause mortality. DESIGN AND SETTING: Propensity score-matched cohort study of ACEIs/ARBs between 2004 and 2019 using UK IQVIA medical research data. METHOD: ADR consultations were identified using standardised designated codes. Propensity scores were calculated based on comorbidities, concomitant medications, frailty, and polypharmacy. Cox's proportional hazard regression model was used to compare the outcomes between patients in ADR and non-ADR groups. In the secondary analysis, treatment- pattern changes following the ADR were examined and the subsequent outcomes were compared. RESULTS: Among 1 471 906 eligible users of ACEIs/ARBs, 13 652 (0.93%) patients had ACEIs/ARBs- related ADR consultation in primary care. Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all- cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27) and secondary prevention cohorts (CVD events: aHR 1.13, 95% CI = 1.05 to 1.21; all-cause mortality: aHR 1.15, 95% CI = 1.09 to 1.21). Half (50.19%) of patients with ADR continued to use ACEIs/ARBs, and these patients had a reduced risk of mortality (aHR 0.88, 95% CI = 0.82 to 0.95) compared with those who discontinued using ACEIs/ARBs. CONCLUSION: This study provides information on the burden of ADR on patients and the health system. The findings call for additional monitoring and treatment strategies for patients affected by ADR to mitigate the risks of adverse clinical outcomes.