Telmisartan 80mg / Hydrochlorothiazide 25mg tablets

Hypertension is a major cause of cardiovascular disease and death worldwide. Low-dose combination therapy is a promising approach for managing hypertension due to its safety and efficacy. This systematic review evaluates the safety and efficacy of a single-pill, low-dose combination of amlodipine, telmisartan, and chlorthalidone for essential hypertension based on evidence from randomized controlled trials (RCTs). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched the Cochrane, Scopus, PubMed, and Web of Science databases until July 01, 2024, using the following search string: (telmisartan) AND (amlodipine) AND (chlorthalidone) AND (randomized OR randomly). The quality of the RCTs was assessed using the revised Cochrane risk of bias tool. The primary endpoint was the mean change in sitting systolic blood pressure (BP), with secondary endpoints including BP target achievement rates, BP response rates, and serious treatment-related adverse events. Overall, three RCTs met the inclusion criteria and exhibited a low risk of bias. The doses in the combination pill ranged from 2.5 to 5 mg of amlodipine, 20 to 80 mg of telmisartan, and 4.167 to 25 mg of chlorthalidone. Control groups varied, including usual care, amlodipine 10 mg, and dual therapy of telmisartan and amlodipine. Results showed significant reductions in mean sitting systolic and diastolic BP, improved BP control and response rates, and a generally safe profile with no significant differences in serious adverse events. Despite encouraging data, results should be interpreted with caution due to heterogeneity in doses and control groups. Further research should address the long-term effects and explore predictors of response to this therapy.

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ImportanceHypertension 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.ObjectivesTo compare the effect of 3 treatment strategies on blood pressure control among persons with untreated hypertension in Africa.Design, setting, and participantsThis 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).InterventionsParticipants 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 Main outcomes and measuresProportion of participants reaching target blood pressure at 12 weeks.ResultsOf 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 relevanceResults 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 registrationClinicalTrials.gov Identifier: NCT04129840.

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