Telmisartan-Chlorthalidone Fixed-Dose Combination at Two Chlorthalidone Dose Levels versus Telmisartan in Uncontrolled Hypertension: A Phase III Trial.

Abstract

Background: Evidence comparing different diuretic doses within fixed-dose combinations (FDCs) remains limited. We evaluated telmisartan/chlorthalidone FDCs according to chlorthalidone dose in patients with blood pressure (BP) inadequately controlled on telmisartan monotherapy.

Methods: In this randomized, double-blind trial, 254 patients with uncontrolled BP [sitting systolic blood pressure (SBP) ≥140 and <180 mmHg; sitting diastolic blood pressure (DBP) <110 mmHg] after a telmisartan run-in period were randomized (1:1:1) to receive either telmisartan/chlorthalidone FDCs (40/12.5 or 40/6.25 mg), or telmisartan 40 mg for 8 weeks. The primary endpoint was the change in sitting SBP from baseline to Week 8.

Results: At Week 8, telmisartan/chlorthalidone FDCs demonstrated greater reductions in sitting SBP compared with telmisartan monotherapy: least-squares mean differences were -9.5 mmHg [95% CI, -13.5 to - 5.6] for the 40/12.5 mg and -6.1 mmHg [95% CI, -10.4 to - 1.9] for the 40/6.25 mg. BP control rates (target BP: SBP/DBP <140/90 mmHg, or < 130/80 mmHg in patients with albuminuric chronic kidney disease or established cardiovascular disease) at Week 8 also favored telmisartan/chlorthalidone FDCs over telmisartan monotherapy (53.2% for the 40/12.5 mg and 43.0% for the 40/6.25 mg versus 32.9% for telmisartan 40 mg). Safety profiles were comparable among treatment groups.

Conclusions: In patients inadequately controlled on telmisartan alone, FDCs of telmisartan with two different doses of chlorthalidone provided greater BP reduction than telmisartan monotherapy without increased safety risk, supporting its role as an effective and well-tolerated treatment option.