Effects of a novel low-dose triple combination on blood pressure variability: results from the TRIDENT trial
T Wang, S Van Der Hoorn, A de silva, C Anderson, A Schutte, A RodgersAbstract
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.