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Randomized Controlled Trial
. 2025 Apr 1;10(4):321-333.
doi: 10.1001/jamacardio.2024.5124.

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

Herry Mapesi  1   2   3 , Martin Rohacek  1   2   3 , Fiona Vanobberghen  2   3 , Ravi Gupta  4 , Herieth Ismael Wilson  1 , Blaise Lukau  4 , Alain Amstutz  5   6   7 , Aza Lyimo  8   9 , Josephine Muhairwe  4   10 , Elizabeth Senkoro  1 , Theonestina Byakuzana  1 , Jacqueline Nkouabi  1 , Geofrey Mbunda  1 , Jamali Siru  1 , Ayesha Tarr  4 , Elsie Ramapepe  4 , Madavida Mphunyane  11 , Johanna Oehri  2   3   12 , Valeriya Nemtsova  12 , Xiaohan Yan  13 , Moniek Bresser  2   3 , Tracy Renée Glass  2   3 , Daniel Henry Paris  2   3 , Günther Fink  2   3 , Winfrid Gingo  8 , Niklaus Daniel Labhardt  2   3   4   5   14 , Thilo Burkard  12   13 , Maja Weisser  1   2   3   14
Affiliations
Randomized Controlled Trial

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

Herry Mapesi et al. JAMA Cardiol. .

Erratum in

  • Error in Abstract and Visual Abstract.
    [No authors listed] [No authors listed] JAMA Cardiol. 2025 Apr 1;10(4):402. doi: 10.1001/jamacardio.2025.0396. JAMA Cardiol. 2025. PMID: 40042829 Free PMC article. No abstract available.

Abstract

Importance: 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.

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

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. 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 ≥140 mm Hg systolic or ≥90 mm Hg diastolic).

Interventions: 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 (≤ 130/80 mm Hg for participants aged <65 years; ≤140/90 mm Hg for those aged ≥65 years).

Main outcomes and measures: Proportion of participants reaching target blood pressure at 12 weeks.

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. 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 = .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).

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. 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.

Trial registration: ClinicalTrials.gov Identifier: NCT04129840.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mapesi reported being employed by Roche outside the submitted work. Prof Rohacek reported receiving grants from Else Kröner Fresenius Foundation outside the submitted work. Prof Labhardt reported receiving travel support from Gilead Sciences and ViiV outside the submitted work. Prof Burkard reported receiving grants from Swiss National Science Foundation, Cardiovascular Research Foundation Basel, AstraZeneca, Daiichi Sankyo, Medtronic, Roche Diagnostics, Novartis, Collabree, and Preventicus and lecture and/or travel fees paid to institution from Servier, Medtronic, Sanofi, Novartis, and Daiichi Sankyo outside the submitted work. Prof Weisser reported receiving grants from the Swiss National Science Foundation for implementation and conduct of the study and travel grants for conference attendance from MSD and Gilead. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participants Flowchart
ARB indicates angiotensin II receptor blocker; BP, blood pressure; CCB, calcium channel blocker; CV, cardiovascular; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HCTZ, hydrochlorothiazide; SBP, systolic blood pressure.
Figure 2.
Figure 2.. Target Blood Pressure Attainment
Analysis based on multiply imputed data. The primary outcome of target blood pressure (defined as systolic blood pressure [SBP] ≤130 mm Hg and diastolic blood pressure [DBP] ≤80 mm Hg for participants aged <65 years and SBP ≤140 mm Hg and DBP ≤90 mm Hg for participants aged ≥65 years) is shown in bars at week 12 and additionally for secondary outcomes at week 4, 8, and 24. ARB indicates angiotensin II receptor blocker; CCB, calcium channel blocker; HCTZ, hydrochlorothiazide.
Figure 3.
Figure 3.. Blood Pressure Response
Analysis based on multiply imputed data. The left upper graph shows mean systolic blood pressure (SBP) values and SD at the study visits (week 4, 8, 12, and 24), the right upper graph shows mean diastolic blood pressure (DBP) values and SD with targets for the different age populations as dashed lines. The lower 2 diagrams show changes of SBP and DBP at the respective time points. ARB, indicates angiotensin II receptor blocker; CCB, calcium channel blocker; HCTZ, hydrochlorothiazide.
See this image and copyright information in PMC

Comment on

  • Blood Pressure Control-Many Paths, 1 Goal.
    Spatz ES, Schwartz JI, Frieden TR. Spatz ES, et al. JAMA Cardiol. 2025 Apr 1;10(4):333-334. doi: 10.1001/jamacardio.2024.5278. JAMA Cardiol. 2025. PMID: 39878963 No abstract available.

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