Triple low-dose pill lowers recurrent stroke risk In survivors of intracerebral bleeding, a once-daily triple low-dose blood-pressure pill reduced recurrent stroke versus placebo.
*Randomized, double-blind, placebo-controlled trial; Level 1b (OCEBM).

Citation

Anderson CS, et al.; Trident Research Group. Three Low-Dose Antihypertensive Agents in a Single Pill after Intracerebral Hemorrhage. N Engl J Med. 2026;394:1571-1582. doi:10.1056/NEJMoa2515043.

Background

Lowering blood pressure is the only proven way to prevent future strokes after spontaneous bleeding into the brain, but long-term control is often poor. This study tested whether adding a single pill with three low-dose medicines improves control and outcomes.

Patients

1670 adults with prior spontaneous intracerebral hemorrhage, stable, with systolic blood pressure 130–160 mm Hg at baseline. Excluded: inability to switch certain blood-pressure drugs, abnormal kidney or liver tests, inability to complete procedures. Only patients who tolerated a 2-week open run-in on the triple pill (including no ≥20% creatinine rise) were randomized.

Intervention

Once-daily single pill: telmisartan 20 mg + amlodipine 2.5 mg + indapamide 1.25 mg, plus usual care.

Control

Matching placebo pill, plus usual care.

Outcome

Primary: first recurrent stroke. Secondary: blood-pressure control, major heart-and-stroke events, cardiovascular death, safety.

Follow-up Period

Median 2.5 years.

Results

Outcome Triple pill Placebo Effect (95% CI) NNT
Recurrent stroke (primary) 4.6% 7.4% Hazard ratio 0.61 (0.41–0.92) 36
Blood pressure controlled at 6 months (<130 mm Hg) 49.9% 26.4% Odds ratio 3.15 (2.53–3.92) 5
Major heart-and-stroke event 6.6% 9.8% Hazard ratio 0.67 (0.47–0.94) 31
Recurrent intracerebral hemorrhage 1.8% 4.4% Hazard ratio 0.40 (0.22–0.73) 39

Analyses were intention-to-treat. Mean systolic blood pressure during follow-up: 127 mm Hg (triple pill) vs 138 mm Hg (placebo). Early stopping due to adverse effects occurred more often with the triple pill (13.6% vs 6.0%), commonly from creatinine increases.

Limitations

Many screened patients were not randomized because the run-in excluded those who could not tolerate the pill, limiting applicability. Most participants lived in Sri Lanka, and recruitment goals were reduced, which may affect certainty and generalizability. More treatment stops from kidney-lab changes may reflect strict trial rules rather than lasting kidney harm.

Funding

Australian government research council; Brazilian Ministry of Health.

Clinical Application

For stable survivors of intracerebral hemorrhage with systolic pressure 130–160, consider a single low-dose triple pill to improve control and reduce recurrent stroke, monitoring kidney labs.