Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data

Baptiste PJ, Wong AY, Schultze A, Clase CM, Leyrat C, Williamson E, Powell E, Mann J, Cunnington M, Teo K, Bangdiwala SI, Gao P, Wing K, Tomlinson L (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Plos Medicine Public Library of Science

Book Volume: 21

Article Number: e1004465

Journal Issue: 9 September

DOI: 10.1371/journal.pmed.1004465

Abstract

Background Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. Methods and findings We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. ApproximatelyAU 17,593: Pleasenotethata Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ ACEi between 1 JanuaryAU 2001: Pleasenotethatallinstanceofthedate and 31 July 2019 were included01 with =01a=2001 median and31 follow-up =07=2019 ofhavebeencha 5.2 years. The 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 an inverse-probability—weighted AU : Pleaseconfirmthattheem Cox proportional - hazards dasheinallinstancesof model for ARB inverse versus - probability ACEi with - heterogeneity by ethnicity assessed on the relative and absolute scale.AU : Pleasenotethatas For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. Conclusions These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Involved external institutions

Queen Mary University of London GB United Kingdom (GB) London School of Hygiene and Tropical Medicine GB United Kingdom (GB) McMaster University CA Canada (CA)

How to cite

APA:

Baptiste, P.J., Wong, A.Y., Schultze, A., Clase, C.M., Leyrat, C., Williamson, E.,... Tomlinson, L. (2024). Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data. Plos Medicine, 21(9 September). https://doi.org/10.1371/journal.pmed.1004465

MLA:

Baptiste, Paris J., et al. "Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data." Plos Medicine 21.9 September (2024).

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