Centre for Primary Care, Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom.
Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS Med. 2024 Sep 16;21(9):e1004465. doi: 10.1371/journal.pmed.1004465. eCollection 2024 Sep.
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.
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. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 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 Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. 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.
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.
由于在美国试验中观察到与 ACEi 使用相关的血管性水肿风险增加，因此国家卫生与保健卓越研究所（National Institute for Health and Care Excellence）建议，对于具有非洲和加勒比血统的人，使用血管紧张素受体阻滞剂（ARB）而非血管紧张素转换酶抑制剂（ACEi）治疗高血压。然而，在英国常规护理中，这些药物在黑人人群中的疗效和风险尚不清楚。
我们应用参考试验模拟方法，利用英国临床实践研究数据链 Aurum 数据（与医院发病统计数据和国家统计局数据相关联），在英国少数民族人群中研究 ARB 和 ACEi 的比较疗效，将结果与 ONTARGET 试验进行基准测试。2001 年 1 月至 2019 年 7 月 31 日期间，约有 17593 名黑人、30805 名南亚人和 524623 名白人患者接受了 ARB/ACEi 的处方，中位随访时间为 5.2 年。主要复合结局是心血管相关死亡、心肌梗死、卒中和心力衰竭住院，各个组成部分作为次要结局进行研究。血管性水肿是安全性终点。我们使用逆概率加权 Cox 比例风险模型评估 ARB 与 ACEi 的结果，通过相对和绝对尺度评估种族异质性。对于主要结局，ARB 组记录了 27327 例（18.0%）事件（事件发生率：每 5.5 人年 25%），ACEi 组记录了 80624 例（19.1%）事件（事件发生率：每 5.5 人年 26%）。我们将结果与 ONTARGET 进行基准测试，观察到主要结局的 HR 为 0.96（95%CI：0.95，0.98），绝对发病率差异（IRD）%为-1.01（95%CI：-1.42，-0.60）每 5.5 人年。我们发现主要结局的种族异质性在乘法（Pint = 0.422）或加法尺度（Pint = 0.287）上均无统计学意义。对于大多数次要结局，结果都是一致的。然而，对于心血管相关死亡，有 37554 人（6.6%）发生，乘法（Pint = 0.002）和加法尺度（Pint < 0.001）上存在强烈的异质性证据。与 ACEi 相比，ARB 与黑人个体更多的事件相关（HR 1.20（95%CI：1.02，1.40）；IRD% 1.07（95%CI：0.10，2.04）；需要治疗的人数（NNH）：93），与白人个体的事件更少相关（HR 0.91（95%CI：0.88，0.93）；IRD% -0.87（95%CI：-1.10，-0.63）；需要治疗的人数（NNT）：115），与南亚个体无差异（HR 0.97（95%CI：0.86，1.09）；IRD% -0.17（95%CI：-0.87，0.53））。对于血管性水肿，ARB 与 ACEi 相比，HR 为 0.56（95%CI：0.46，0.67），乘法尺度上无异质性（Pint = 0.306）。然而，在加法尺度上存在异质性（Pint = 0.023）。黑人个体的绝对风险较高（IRD% -0.49（95%CI：-0.79，-0.18）；NNH：204），与白人个体（IRD% -0.06（95%CI：-0.09，-0.03）；NNH：1667）相比，差异有统计学意义，与南亚个体（ARB 与 ACEi 相比，IRD% -0.05（95%CI：-0.15，0.05））无差异。
这些结果表明，ACEi 和 ARB 对某些结局的疗效在某些种族中存在差异，并提示英国目前推荐 ARB 而非 ACEi 用于黑人个体的指南建议可能带来不良后果。
