Comparative Efficacy and Safety of Telmisartan–Amlodipine versus Amlodipine–Chlorthalidone Combination Therapy in Patients with Uncontrolled Essential Hypertension: A Randomised Controlled Trial
Abstract
Received: 12-09-2026 Revised: 19-09-2026 Accepted: 21-09-2026 Background: Hypertension uncontrolled on monotherapy represents a common clinical challenge, yet the optimal fixed-dose combination for treatment intensification remains uncertain. We compared the efficacy and safety of telmisartan–amlodipine versus amlodipine–chlorthalidone in patients with uncontrolled hypertension despite stable monotherapy. Methods: In this 12-week, randomised, open-label, parallel-group trial conducted at a tertiary care centre in India, 186 adults aged 30–70 years with uncontrolled essential hypertension on stable monotherapy were randomised 1:1 to receive fixed-dose telmisartan 40 mg–amlodipine 5 mg (n = 93) or amlodipine 5 mg–chlorthalidone 12.5 mg (n = 93) once daily. The primary outcome was change in mean seated office systolic blood pressure (SBP) from baseline to week 12, analysed using ANCOVA with baseline SBP as a covariate. Secondary outcomes included changes in diastolic blood pressure (DBP), blood pressure control rate, adherence, and adverse events. Results: Baseline characteristics were well balanced between groups. Mean SBP reduction was 25.8 mmHg with telmisartan–amlodipine and 23.0 mmHg with amlodipine–chlorthalidone (adjusted between-group difference: −2.8 mmHg; 95% CI: −5.6 to −0.1; p = 0.04). DBP reductions were similar between groups (−11.8 vs −9.6 mmHg; adjusted difference: −1.5 mmHg; 95% CI: −3.2 to 0.2; p = 0.08). Blood pressure control was achieved in 68.9% versus 62.5% of participants, respectively (p = 0.37). Hypokalemia occurred exclusively with amlodipine–chlorthalidone (6.5% vs 0%; p = 0.01); peripheral oedema was more frequent with telmisartan–amlodipine (7.5% vs 3.2%; p = 0.19). Adherence exceeded 88% in both groups. Conclusions: Both fixed-dose combinations provided substantial blood pressure reduction in patients with uncontrolled hypertension on monotherapy. Telmisartan–amlodipine conferred modestly greater systolic blood pressure reduction and a more favourable metabolic profile, supporting its preferential use for treatment intensification.