Key result
Valsartan/amlodipine/chlorthalidone triple therapy reduces systolic BP ~11 mmHg versus valsartan/amlodipine.
Why the study?
Many patients with hypertension require three or more agents to achieve target blood pressure, but the efficacy and safety of triple therapy with valsartan, amlodipine, and chlorthalidone after dual therapy failure needed evaluation.
Does triple therapy with valsartan, amlodipine, and chlorthalidone reduce systolic blood pressure in patients with essential hypertension inadequately controlled on valsartan/amlodipine?
RCT (n=193)
Double-blind
1:1
Yes
Does triple therapy with valsartan, amlodipine, and chlorthalidone reduce systolic blood pressure in patients with essential hypertension inadequately controlled on valsartan/amlodipine?
Mean Difference: -10.99 (95% CI -14.56–-7.41)
Absolute Event Rate: -19.7% vs -8.71%
p-value: p=< 0.0001
Triple combination therapy with valsartan, amlodipine, and chlorthalidone provides significantly greater blood pressure reduction than dual therapy in patients with inadequately controlled essential hypertension.
Supports adding chlorthalidone for uncontrolled patients on dual ARB/CCB; extends RCT evidence for this triple regimen.
Objective: Many patients with hypertension require three or more agents to achieve target blood pressure (BP). This randomized, double-blind study evaluated the efficacy/safety of triple therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients with essential hypertension who did not achieve adequate BP control with Val/Aml combination therapy. Design and method: A randomized, double-blind, multicenter, phase 3 clinical trial was conducted in South Korea. Patients who failed to respond adequately to 4 weeks of Val/Aml 80/5 mg were randomized in a 1:1 ratio to either Val/Aml/CTD 80/5/12.5 mg and placebo for Val/Aml 80/5 mg (study group) or placebo for Val/Aml/CTD 80/5/12.5 mg and Val/Aml 80/5 mg (control group) using a double-dummy design to maintain blinding. After 2 weeks of administering assigned investigational medicinal products, participants in the study group received Val/Aml/CTD 160/5/25 mg and placebo for Val/Aml 160/5 mg, while those in the control group received placebo for Val/Aml/CTD 160/5/25 mg and Val/Aml 160/5 mg for 6 weeks. Primary endpoint was determined by how mean sitting systolic blood pressure (MSSBP) varied between the baseline and week 8. The incidence of adverse events was also evaluated. Results: Of the 193 randomized patients, 193 conducted efficacy analyses, and 178 competed the study. The least squares (LS) mean (standard error [SE]) change in MSSBP was -19.70 (1.31) mmHg in the Val/Aml/CTD group and -8.71 (1.26) mmHg in the control group. The LS mean difference (SE) in MSSBP change between the two groups was -10.99 (1.81) mmHg (95% confidence interval [CI], -14.56 to -7.41), indicating a statistically significant greater reduction in the Val/Aml/CTD group compared with the control group (p < 0.0001). The incidence of serious adverse events was 1.98% in the control group, whereas no serious adverse events were reported in the Val/Aml/CTD group (p = 0.4985). Conclusions: In patients with essential hypertension who exhibited an inadequate response to Val/Aml combination therapy, the triple combination of Val/Aml/CTD demonstrated favorable efficacy and safety profiles.
No takes yet. Share an insight, caveat, or question.
Pyun et al. (2026) conducted an RCT in essential hypertension (n=193). valsartan, amlodipine, and chlorthalidone vs. valsartan/amlodipine was evaluated on change in mean sitting systolic blood pressure (MSSBP) between baseline and week 8 (MD -10.99, 95% CI -14.56 to -7.41, p=< 0.0001). Triple therapy with valsartan, amlodipine, and chlorthalidone significantly reduced mean sitting systolic blood pressure compared to valsartan/amlodipine (mean difference -10.99 mmHg; P<0.0001).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: