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Treatment Strategies to Control Blood Pressure in People With Hypertension in Tanzania and Lesotho: A Randomized
Herry Mapesi1,2,3, Martin Rohacek1,2,3, Fiona Vanobberghen2,3
1Ifakara Health Institute, Ifakara Branch, Ifakara, United Republic of Tanzania.
Insights
A low-dose two-pill hypertension treatment strategy was noninferior to monotherapy in African adults. However, neither two-pill nor three-pill strategies demonstrated superiority over stepped monotherapy for blood pressure control.
Area of Science:
- Cardiology
- Public Health
- Clinical Trials
Background:
- Hypertension is a leading cardiovascular risk factor in Africa.
- Recent WHO guidelines suggest initiating dual antihypertensive therapy.
- The efficacy and tolerability of low-dose triple combination therapy require further investigation.
Purpose of the Study:
- To compare the effectiveness of three distinct treatment strategies for blood pressure control in individuals with untreated hypertension in Africa.
- To evaluate the noninferiority of a two-pill strategy versus full-dose monotherapy with stepped escalation.
- To assess the superiority of a low-dose three-pill strategy compared to monotherapy with monthly titration.
Main Methods:
- An open-label, parallel, 3-arm randomized clinical trial was conducted in rural Lesotho and Tanzania.
- 1268 participants with untreated hypertension were randomized into three groups: stepped monotherapy, a two-pill strategy, or a three-pill strategy.
- Treatment involved monthly titration until blood pressure targets were met.
Main Results:
- The two-pill strategy (56% achieving target BP) was noninferior to stepped monotherapy (51%).
- The three-pill strategy (57%) and two-pill strategy (55%) did not show superiority over stepped monotherapy (49%).
- Wide confidence intervals limit definitive conclusions on the superiority of multi-pill strategies.
Conclusions:
- In African adults with uncomplicated, untreated hypertension, initiating a low-dose two-pill regimen is noninferior to stepped monotherapy.
- Low-dose two-pill and three-pill strategies were not found to be superior to stepped monotherapy.
- Further research is needed to clarify the clinical impact of multi-pill strategies due to wide confidence intervals.
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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