{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T00:55:17Z","timestamp":1794099317971,"version":"4.8.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"Importance<\/jats:title>Hypertension is the primary cardiovascular risk factor in Africa. Recently revised World Health Organization guidelines recommend starting antihypertensive dual therapy; clinical efficacy and tolerability of low-dose triple combination remain unclear.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To compare the effect of 3 treatment strategies on blood pressure control among persons with untreated hypertension in Africa.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>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. Recruitment lasted from March 5, 2020, to March 30, 2022. The setting was 2 hospitals in rural Lesotho and Tanzania. Participants included nonpregnant Black African individuals 18 years and older with uncomplicated, untreated hypertension (standardized office blood pressure \u2265140 mm Hg systolic or \u226590 mm Hg diastolic).<\/jats:p><\/jats:sec>Interventions<\/jats:title>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). Drugs were up titrated monthly until reaching the target blood pressure (\u2264 130\/80 mm Hg for participants aged &amp;lt;65 years; \u2264140\/90 mm Hg for those aged \u226565 years).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Proportion of participants reaching target blood pressure at 12 weeks.<\/jats:p><\/jats:sec>Results<\/jats:title>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. 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. 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<\/jats:italic>\u2009=\u2009.12 and aOR, 1.28; 95% CI, 0.91-1.79; P<\/jats:italic>\u2009=\u2009.16 for the 2-pill and 3-pill vs stepped monotherapy strategies, respectively).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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. Two-pill and 3-pill low-dose strategies were not superior to stepped monotherapy. Wide CIs preclude the ability to rule out potentially clinically important effects of the additional pill strategies for hypertension control.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04129840<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2024.5124","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T17:41:44Z","timestamp":1738172504000},"page":"321","source":"Crossref","is-referenced-by-count":13,"title":["Treatment Strategies to Control Blood Pressure in People With Hypertension in Tanzania and Lesotho"],"prefix":"10.1001","volume":"10","author":[{"given":"Herry","family":"Mapesi","sequence":"first","affiliation":[{"name":"Ifakara Health Institute, Ifakara Branch, Ifakara, United Republic of Tanzania"},{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, 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