Key result
Low-dose triple therapy reduces systolic blood pressure variability by ~2 mmHg SD versus placebo.
Why the study?
Blood pressure variability is an independent predictor of cardiovascular events and stroke, and although a low-dose triple combination reduced mean BP and stroke after intracerebral haemorrhage in TRIDENT, its effects on BP variability remained unclear.
Does a low-dose triple single-pill combination of telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg reduce blood pressure variability compared with placebo in patients with prior intracerebral haemorrhage?
RCT (n=1,557)
Double-blind
Randomized
Yes
Does a low-dose triple single-pill combination of telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg reduce blood pressure variability compared with placebo in patients with prior intracerebral haemorrhage?
In patients with prior intracerebral haemorrhage, a low-dose triple single-pill antihypertensive combination reduces standard metrics of blood pressure variability (SD, CV, ARV) but not variability independent of the mean (VIM), indicating the reduction in variability is predominantly driven by mean blood pressure lowering.
Background Blood pressure variability (BPV) is an important predictor of cardiovascular events and stroke, independent of mean blood pressure (BP). In TRIDENT trial, a low-dose triple combination reduced mean BP by 9mmHg and reduced stroke compared with placebo in patients with prior intracerebral haemorrhage. However, its effects on BPV remain unclear. Methods TRIDENT (n=1670) was a multinational, double-blind, randomised, placebo-controlled trial in patients with prior intracerebral haemorrhage and systolic BP 130–160 mmHg who completed a 2-week single-blind active run-in phase. Participants were randomised to a triple single-pill combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg or matching placebo, in addition to usual care, with a mean follow-up of 3 years. BPV was assessed using the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM). Between-group differences were assessed using a simple two-sample t-test. Results A total of 1557 patients (mean age: 58 years; 33% female) with >1 follow-up BP measurement was included. Compared with placebo, the triple single-pill combination significantly reduced systolic BPV, measured by SD (−2.05 mmHg; 95% CI: −2.73 to −1.36; p<0.001), CV (−0.82%; 95% CI −1.29 to −0.34; p<0.001) and ARV (−2.47 mmHg; 95% CI −3.37 to −1.58; p<0.001), but not VIM (+0.07; 95% CI −0.55 to 0.69; p=0.83). Similar reductions were observed for diastolic BPV across SD (−0.84 mmHg; 95% CI −1.24 to −0.43; p<0.001), CV (−0.47%; 95% CI −0.92 to −0.02; p=0.039) and ARV (−0.84 mmHg; 95% CI −1.39 to −0.30; p=0.003), with no difference in VIM (−0.07; 95% CI −0.44 to 0.30; p=0.70). Conclusions In patients with prior intracerebral haemorrhage receiving usual care, a low-dose triple single-pill combination reduced SD, CV and ARV of systolic and diastolic BP variability compared with placebo, but not VIM. As VIM adjusts for mean BP, the lack of a significant difference in VIM indicates that reductions in SD, CV and ARV were predominantly attributable to mean BP lowering.
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Wang et al. (2026) conducted an RCT in Prior intracerebral haemorrhage and systolic BP 130-160 mmHg (n=1,557). Triple single-pill combination (telmisartan, amlodipine, indapamide) vs. Matching placebo in addition to usual care was evaluated on Systolic blood pressure variability (standard deviation) (MD -2.05 mmHg, 95% CI -2.73 to -1.36, p=<0.001). Low-dose triple therapy reduced systolic BPV by SD (−2.05 mmHg; 95% CI −2.73 to −1.36; P<0.001), CV, and ARV vs placebo, but not VIM (+0.07; P=0.83).
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