Introduction: 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.
Methods: In this phase III, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50 mg) and telmisartan (40 mg) were included. Patients received either of the following FDC for 24 weeks: metoprolol (25 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC1; n = 139) or metoprolol (50 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (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 24 weeks. Secondary efficacy endpoints included proportion of patients achieving < 90 mmHg SeDBP (SeDBP responder) and < 140 mmHg SeSBP (SeSBP responder) at weeks 12, 16, 20, and 24. Safety was assessed throughout the study.
Results: A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96 mmHg; FDC2, 165/98 mmHg) to week 24 (FDC1, 128/82 mmHg; FDC2, 131/83 mmHg) was statistically significant (both groups p < 0.0001). Within FDC1 and FDC2, the mean change from baseline to week 24 in SeDBP (82.60 mmHg and 83.09 mmHg) and SeSBP (128.07 mmHg and 131.29 mmHg) was statistically significant (both groups p < 0.0001). At week 24, 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.
Conclusion: Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy.
Clinical trial registration: CTRI/2016/11/007491.
Keywords: Chlorthalidone; Coronary artery disease; Efficacy; Essential hypertension; Fixed-dose combination; Medication adherence; Metoprolol; Safety; Telmisartan; Triple combination.
The increasing prevalence of hypertension in India requires immediate attention. To adequately manage blood pressure and ensure compliance to medications, innovative treatment options involving combination therapy with three or more drugs to treat hypertension need to be explored. Fixed-dose combination (FDC) of three antihypertension drugs, viz., metoprolol, telmisartan, and chlorthalidone, were tested in Indian patients who could not respond adequately to dual treatment. The rationale behind using a combination of three drug types was to take advantage of the complementary actions of each drug class for an enhanced treatment effect. The two variants of FDCs were tested in 254 adults with the most common form of heart disease, i.e., stable coronary artery disease. Changes in seated diastolic and systolic blood pressure (SeDBP and SeSBP) were measured to assess the effectiveness of the FDC. The mean changes in SeDBP and SeSBP were statistically significant by the end of the study, i.e., it determined that results are not explainable by chance alone. A greater proportion of patients (range 74–84%) achieved their target BPs with the FDC used in the study. The FDC variants were well tolerated without any reports of serious adverse events or deaths. Overall, this triple combination therapy option was effective and considered safe to be administered to hypertensive Indian adults with stable coronary artery disease who did not respond adequately to dual antihypertension therapy.
© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.