SINGLE-PILL COMBINATION OF THIRD-DOSE TRIPLE ANTIHYPERTENSIVE THERAPY VERSUS STANDARD-DOSE MONOTHERAPY IN PATIENTS WITH MILD TO MODERATE HYPERTENSION

Abstract

Objective: The study compared the single-pill combination of third-dose triple antihypertensive therapy (amlodipine 1.67 mg, losartan potassium 16.67 mg, chlorthalidone 4.17 mg) with standard-dose monotherapy (amlodipine 5mg) in reducing systolic blood pressure (SBP) among patients with mild to moderate hypertension. Design and method: This was a multicenter, randomized, double-blind, active-controlled, parallel-group phase III noninferiority trial. Eligible participants aged >=19 years with SBP >=140 to <180 mmHg and diastolic blood pressure (DBP) <110 mmHg after 4 weeks placebo run-in period were randomized to either 8 weeks of combination therapy (ALC) or monotherapy (A5). The primary efficacy endpoint, noninferiority in SBP reduction, was assessed using the upper limit of the one-sided 97.5% confidence interval (97.5%CI) for the difference in SBP reduction between treatments at week 8, with a noninferiority margin of 3 mmHg. Results: The efficacy endpoint analysis included 167 and 166 in the ALC and A5 groups. After 8 weeks, the ALC and A5 groups showed SBP reductions of -18.3±11.9 and -19.4±12.5, respectively, and DBP reductions of -8.5±7.3 and -9.8±7.0 mmHg, respectively (p>0.025 for both). The unadjusted least-square mean (LSM) difference in SBP reduction was 1.15 mmHg, with a 97.5%CI upper limit of 3.51 mmHg. More female patients were allocated to the A5 than the ALC groups (47.6% vs. 34.1%, p=0.012). Both treatments exhibited greater SBP reduction in women than men (-21.4 vs. -16.8 mmHg, p=0.009 in the ALC group; -21.9 vs -17.1 mmHg, p<0.001 in the A5 group). The sex-adjusted LSM difference in SBP reduction was 0.46 mmHg, with a 97.5%CI upper limit of 2.79 mmHg. The response rates (achieving SBP <140 mmHg and DBP <90 mmHg and/or reduction of SBP >=20 mmHg and/or DBP >=10 mmHg from baseline) were 73.1% for ALC and 75.3% for A5 groups (p=0.633). Adverse drug reactions (ADRs) occurred in 3 patients receiving ALC and 5 patients receiving A5, all being mild. Conclusions: The study demonstrated that the single-pill third-dose triple antihypertensive therapy is comparable to standard-dose monotherapy in reducing SBP over 8 weeks without increasing ADRs, providing further support for the low-dose combination antihypertensive drugs in the initial treatment of hypertension. (NCT05362110)