Effects of a novel low-dose triple combination antihypertensive pill on blood pressure, according to background blood pressure medications: results from the TRIDENT trial

Background There is increasing interest in the potential for low-dose combination antihypertensives to improve blood pressure (BP) control, but limited evidence exists of their long-term effects or efficacy when added to other regimens. Methods In TRIDENT, a multinational, double-blind, randomized, placebo-controlled trial of patients with prior intracerebral haemorrhage and a systolic BP 130-160mmHg who successfully completed a 2-week, single-blind, active run-in phase, eligible patients were randomized to a triple-pill containing telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg or matching placebo, on top of usual care. For this analysis, placebo-corrected BP reductions were assessed according to background BP regimen in the intention-to-treat population. Results A total of 1670 patients underwent randomization at 57 sites in 10 countries. Baseline characteristics were balanced with mean age 58 years and 34% female. After the run-in phase, mean systolic BP was 127mmHg on a mean 1.2 classes of background antihypertensive drugs. The overall BP difference at 6 weeks was 15/7 mmHg and averaged 9/4 mmHg over all follow-up, with attenuation principally due to drop-in: at final follow-up visit, the mean number of background BP drugs was 2.1 in the placebo group and remained 1.2 in the treatment group. At week 6, BP differences vs placebo were 16/9, 16/7, 15/8 and 12/5 mmHg (all p<0.001; p for heterogeneity 0.4), according to whether participants received 0, 1, 2 or 3+ background BP medications, respecively. When analyses were restricted to those whose background BP regimen comprised one or more medications in the same class as the intervention (ARB, calcium channel blocker, diuretic; n=994), BP differences vs placebo were 16/8, 15/8 and 12/5 mmHg according to whether participants received 1, 2 or 3 background BP medications (all p<0.01). With background beta-blocker monotherapy (n=41), the systolic and diastolic BP differences were 20 mmHg (p<0.001) and 6 mmHg (p=0.06), respectively. Conclusions This novel low-dose triple therapy achieved large and sustained BP reductions when used alone, and these reductions were only modestly attenuated when added on top of 1-3 other classes of BP medications.TRIDENT BP abstract for ESC final.jpg