Fixed-dose triple-combination therapy may offer a strategy to improve blood pressure reduction while maintaining treatment simplicity. In a randomized, double-blind, multicenter phase 3 trial conducted in South Korea, investigators evaluated the efficacy and safety of a triple combination of valsartan, amlodipine, and chlorthalidone in patients with essential hypertension who had not achieved adequate blood pressure control after 4 weeks of treatment with valsartan and amlodipine. The findings were presented at the ESH Congress 2026.

A total of 193 patients were randomized in a 1:1 ratio to receive either valsartan/amlodipine/chlorthalidone or continued valsartan/amlodipine therapy using a double-dummy design. Following an initial two-week treatment period, doses were escalated and continued for an additional six weeks. 

Findings

• The least-squares mean reduction in mean sitting systolic blood pressure at week 8 was 19.70 mmHg in the valsartan/amlodipine/chlorthalidone group compared with 8.71 mmHg in the valsartan/amlodipine group.
• Triple therapy achieved an additional 10.99 mmHg reduction in systolic blood pressure compared with dual therapy (95% CI, –14.56 to –7.41; p<0.0001).
• The blood pressure-lowering effect of the triple-combination regimen was significantly greater than that achieved with continued valsartan/amlodipine treatment alone.
• No serious adverse events were reported in the valsartan/amlodipine/chlorthalidone group during the study period.
• Serious adverse events occurred in 1.98% of patients receiving valsartan/amlodipine therapy alone, with no statistically significant difference between groups (p=0.4985).

The findings indicate that adding chlorthalidone to valsartan and amlodipine provides substantially greater systolic blood pressure reduction in patients with inadequately controlled hypertension.