Triple Low-Dose Antihypertensive Pill After Intracerebral Hemorrhage

Key Takeaways

• Recurrent stroke was less frequent with the fixed low-dose triple pill than with placebo during follow-up.
• Mean systolic blood pressure during follow-up and major cardiovascular events were lower in the triple-pill group.
• Serious adverse events occurred in both groups, while early discontinuation was more frequent with the triple pill and often involved serum creatinine increases.

Among clinically stable patients with prior intracerebral hemorrhage, a once-daily fixed low-dose triple pill was associated with fewer recurrent strokes than placebo over a median follow-up of 2.5 years, with a hazard ratio of 0.61 for first recurrent stroke. Participants entered the study with baseline systolic blood pressure between 130 and 160 mm Hg. The fixed-dose combination was used alongside usual antihypertensive treatment when patients were already receiving it.

In a multinational double-blind randomized trial, investigators enrolled clinically stable patients with a history of intracerebral hemorrhage and baseline systolic blood pressure of 130 to 160 mm Hg. Before randomization, all participants completed a 2-week active run-in during which they received a once-daily fixed pill containing telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg. The regimen was added to standard antihypertensive treatment when present. Investigators randomized 1670 patients with a mean age of 58 years, assigning 833 to continue the triple pill and 837 to receive matching placebo.

At a median follow-up of 2.5 years, recurrent stroke occurred in 38 of 833 patients (4.6%) assigned to the triple pill and in 62 of 837 patients (7.4%) assigned to placebo. In the recurrent stroke and blood-pressure results, mean systolic blood pressure during follow-up was 127 mm Hg with the triple pill and 138 mm Hg with placebo. Major cardiovascular events occurred in 6.6% and 9.8% of patients during follow-up, respectively, with P=0.04. These prespecified secondary outcomes favored the triple-pill group during follow-up.

Safety findings showed events in both randomized groups, with serious adverse events occurring in 23.2% of patients assigned to the triple pill and 26.0% assigned to placebo. Early discontinuation due to an adverse event was more frequent with the triple pill, affecting 13.6% of patients versus 6.0% with placebo. The most common adverse event leading to discontinuation was a serum creatinine increase of 20% or more.