Treatment Strategies to Control Blood Pressure in People With Hypertension in Tanzania and Lesotho: A Randomized Clinical Trial.

Recently revised World Health Organization guidelines recommend starting antihypertensive dual therapy; clinical efficacy and tolerability of low-dose triple combination remain unclear.

最近修订的世界卫生组织指南推荐开始使用降压双重治疗；低剂量三联疗法的临床疗效和耐受性仍不明确。

Background

To compare the effect of 3 treatment strategies on blood pressure control among persons with untreated hypertension in Africa.

比较三种治疗策略对非洲未治疗高血压患者血压控制的影响。

DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, parallel, 3-arm randomized clinical trial to evaluate noninferiority of a strategy starting 2 pills vs full-dose monotherapy with stepped escalation (noninferiority margin 10%) and superiority of starting low-dose 3 pills vs monotherapy allowing for monthly up titration.

设计、环境和参与者：这是一项开放标签、平行的3臂随机临床试验，旨在评估起始2片药物策略与全剂量单药治疗逐步升级（非劣效边界10%）的非劣效性，以及起始低剂量3片药物与单药治疗每月上调剂量的优越性。

Recruitment lasted from March 5, 2020, to March 30, 2022.

招募工作从2020年3月5日持续到2022年3月30日。

The setting was 2 hospitals in rural Lesotho and Tanzania.

研究地点设在莱索托和坦桑尼亚的两家乡村医院。

Participants included nonpregnant Black African individuals 18 years and older with uncomplicated, untreated hypertension (standardized office blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic).

参与者包括18岁及以上的非怀孕黑人非洲人，患有未复杂化、未治疗的高血压（标准化办公室血压≥140毫米汞柱收缩压或≥90毫米汞柱舒张压）。

Methods

Participants were randomized 2:2:1 to stepped monotherapy (amlodipine, 10 mg, with escalation to add hydrochlorothiazide if needed), 2-pill strategy (amlodipine, 5 mg; losartan, 50 mg), or 3-pill strategy (amlodipine, 2.5 mg; losartan, 12.5 mg; hydrochlorothiazide, 6.25 mg).

参与者被随机分为2:2:1的三组，分别接受逐步单药治疗（氨氯地平10毫克，如有需要可增加氢氯噻嗪），双药策略（氨氯地平5毫克；洛沙坦50毫克），或三药策略（氨氯地平2.5毫克；洛沙坦12.5毫克；氢氯噻嗪6.25毫克）。

Drugs were up titrated monthly until reaching the target blood pressure (≤ 130/80 mm Hg for participants aged <65 years; ≤140/90 mm Hg for those aged ≥65 years).

药物每月上调剂量，直至达到目标血压（<65岁患者≤130/80毫米汞柱；≥65岁患者≤140/90毫米汞柱）。

main_outcomes_and_measures

Proportion of participants reaching target blood pressure at 12 weeks.

12周时达到目标血压的参与者比例。

Results

Of 1761 participants screened, 1268 were enrolled (median [IQR] age, 54 [45-65] years; 914 female [72%]), with 505 in the monotherapy cohort, 510 in the 2-pill cohort, and 253 in the 3-pill cohort.

在筛选的1761名参与者中，有1268名被纳入研究（中位年龄[四分位数间距]为54[45-65]岁；914名女性[72%]），其中505名在单药治疗队列，510名在双药治疗队列，253名在三药治疗队列。

In noninferiority analyses, 207 of 370 participants (56%) receiving the 2-pill strategy and 173 of 338 participants (51%) receiving the stepped monotherapy strategy achieved the blood pressure target (adjusted odds ratio [aOR], 1.18; 95% CI, 0.87-1.61), fulfilling noninferiority.

在非劣效性分析中，接受双药策略的370名参与者中有207名（56%）和接受逐步单药治疗策略的338名参与者中有173名（51%）达到了血压目标（调整后的优势比[aOR]，1.18；95%置信区间[CI]，0.87-1.61），满足了非劣效性。

In superiority analyses after multiple imputation for missing outcome data, 57% of participants receiving the 3-pill strategy, 55% receiving the 2-pill strategy, and 49% receiving the stepped monotherapy strategy reached the target blood pressure (aOR, 1.24; 95% CI, 0.94-1.63; P = .12 and aOR, 1.28; 95% CI, 0.91-1.79; P = .16 for the 2-pill and 3-pill vs stepped monotherapy strategies, respectively).

在对缺失结果数据进行多重插补后的优势分析中，接受3药片策略的参与者有57%，接受2药片策略的有55%，而接受逐步单药治疗策略的有49%达到了目标血压（调整后优势比aOR为1.24；95%置信区间CI为0.94-1.63；P = .12，以及aOR为1.28；95% CI为0.91-1.79；P = .16，分别对应2药片和3药片与逐步单药治疗策略的比较）。

conclusions_and_relevance

Results of this randomized clinical trial show that in 2 African settings, for adults with uncomplicated untreated hypertension, a strategy starting a 2-pill low-dose treatment was noninferior to starting stepped monotherapy.

这项随机临床试验的结果显示，在两个非洲地区，对于未接受治疗的单纯性高血压成人，开始使用2药片低剂量治疗的策略与开始逐步单药治疗策略相比，并不逊色。

Two-pill and 3-pill low-dose strategies were not superior to stepped monotherapy.

两药和三药低剂量策略并不优于逐步单药治疗。

Wide CIs preclude the ability to rule out potentially clinically important effects of the additional pill strategies for hypertension control.

宽置信区间限制了我们排除额外药物策略对高血压控制可能具有临床重要影响的能力。

trial_registration

ClinicalTrials.gov Identifier: NCT04129840.

临床试验注册号：NCT04129840。