Comparative effectiveness of ARB and ACEi for cardiovascular outcomes and risk of angioedema among different ethnic groups in England: an analysis in the UK Clinical Practice Research Datalink with emulation of a reference trial (ONTARGET)

Abstract

AbstractObjectiveTo study the comparative effectiveness of angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEi) in ethnic minority groups in the UK.DesignObservational cohort study using a reference trial emulation approach benchmarked against the ONTARGET trial.SettingUK Clinical Practice Research Datalink Aurum data from 01/01/2001-31/07/2019.ParticipantsBlack, South Asian, or White patients treated with ARB or ACEi who met the ONTARGET trial criteria.Main outcome measuresThe primary composite outcome was: cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using a propensity-score—weighted Cox proportional hazards model for ARB vs ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale.Results17,593 Black, 30,805 South Asian, and 524,623 White patients were included. We benchmarked results against ONTARGET comparing ARB with ACEi for the primary outcome (hazard ratio [HR] 0.96, 95% CI: 0.95 to 0.98) and found no evidence of treatment effect heterogeneity (Pint=0.422). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, there was strong evidence of heterogeneity (Pint=0.002), with ARB associated with more events in Black individuals and with fewer events in White individuals compared to ACEi, and no differences in South Asian individuals. For angioedema, HR 0.56 (95% CI: 0.46 to 0.67) for ARB vs ACEi (Pint=0.306). Absolute risks were higher in Black individuals, with number-needed-to-harm of 204 in Black individuals compared with 2000 in South Asian individuals and 1667 in White individuals (Pint=0.023).ConclusionsThese results demonstrate variation in drug effects of ACEi and ARB by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.What is already known on this topicCurrent UK National Institute for Health and Care Excellence (NICE) recommendations for treatment of hypertension includes ethnicity (Black vs non-Black) as a determinant of treatment choice and recommend an ARB in preference to an ACEi in Black patients based on the risk of angioedema in this groupDespite being at increased risk of hypertension and cardiovascular disease, little is known about comparative treatment effectiveness and risk of ARB and ACEi among South Asian patients in the UKReference trial emulation (considering study design and benchmarking against an existing randomised trial), followed by analysis of effects in trial-underrepresented groups can add confidence to findings of observational research and bridge gaps in evidenceWhat this study addsIn this propensity-score—weighted cohort study of self-reported Black, South Asian and White patients at high-risk of cardiovascular disease in the UK, ARB were as effective as ACEi at preventing most cardiovascular outcomes. However, for cardiovascular death, treatment of 93 (95% CI: 49 to 1000) Black patients with ARB rather than ACEi was associated with prevention of one cardiovascular death, compared with the opposite effect in White patients: treatment of 115 (95% CI: 91 to 159) White patients with ACEi rather than ARB was associated with the prevention of one cardiovascular death. No difference between the two drugs was observed among South Asian patients.Relative risks of angioedema, ARB vs ACEi were similar across all ethnic groups but because of the increased incidence in Black patients, there was a marked difference in the number needed to harm for ARB compared to ACEi use: 204 (95% CI: 127 to 556) in Black patients and 1667 (95% CI: 1111 to 3333) in White patients. There was no difference in angioedema risk between the drugs in South Asian patients.South Asian and White patients starting ACEi experienced a greater fall in blood pressure than those starting ARB. There was no difference in fall in blood pressure between the drugs for Black patients.