Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: PhaseIII Study.

Abstract

The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy. In this phaseIII, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50mg) and telmisartan (40mg) were included. Patients received either of the following FDC for 24weeks: metoprolol (25mg), telmisartan (40mg), and chlorthalidone (12.5mg) (FDC1; n = 139) or metoprolol (50mg), telmisartan (40mg), and chlorthalidone (12.5mg) (FDC2; n = 115) tablets once daily. The FDCs were developed using the novel Wrap Matrix™ platform technology. Primary endpoint assessed the mean change in seated diastolic blood pressure (SeDBP) and seated systolic blood pressure (SeSBP) from baseline to 24weeks. Secondary efficacy endpoints included proportion of patients achieving < 90mmHg SeDBP (SeDBP responder) and < 140mmHg SeSBP (SeSBP responder) at weeks12, 16, 20, and 24. Safety was assessed throughout the study. A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96mmHg; FDC2, 165/98mmHg) to week24 (FDC1, 128/82mmHg; FDC2, 131/83mmHg) was statistically significant (both groups p < 0.0001). Within FDC1 and FDC2, the mean change from baseline to week24 in SeDBP (82.60mmHg and 83.09mmHg) and SeSBP (128.07mmHg and 131.29mmHg) was statistically significant (both groups p < 0.0001). At week24, in FDC1, 80.15% and 84.73% were SeDBP and SeSBP responders, respectively; in FDC2, 79.46% and 74.11% were SeDBP and SeSBP responders, respectively. No serious adverse events or deaths were reported. Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy. CTRI/2016/11/007491.