TRIDENT Cognitive
(2026)Objective
Pre-specified secondary analysis of TRIDENT testing whether a triple low-dose antihypertensive single-pill combination after ICH reduces cognitive decline, dementia, and MRI markers of cerebral small vessel disease vs placebo.
Study Summary
• Alive without dementia: 56.3% vs 55.0% (NS).
• MOCA (ordinal): OR 1.41 (0.98-1.96).
• WMH number: 49 vs 48 (NS); recent subcortical infarct 1.5% vs 1.2%.
• CMB number 1 (0-3) vs 1 (0-3); CSS 1 (1-1) vs 1.5 (1-2). No difference in cognitive or CSVD MRI markers.
• MOCA (ordinal): OR 1.41 (0.98-1.96).
• WMH number: 49 vs 48 (NS); recent subcortical infarct 1.5% vs 1.2%.
• CMB number 1 (0-3) vs 1 (0-3); CSS 1 (1-1) vs 1.5 (1-2). No difference in cognitive or CSVD MRI markers.
Intervention
Triple low-dose antihypertensive single pill (indapamide + perindopril + amlodipine) vs placebo, after 2-week run-in
Inclusion Criteria
Sri Lanka (67%) and other countries. Stable survivors of ICH; SBP 130-160 mmHg; underwent 2-week run-in phase. Age ~58, HTN 80%, deep ICH 77%, baseline MOCA <22 in ~46%.
Study Design
Arms: Triple-pill vs placebo
Patients per Arm: Intervention n=833 (cognitive 501; MRI 374) vs Control n=837 (cognitive 494; MRI 359). FU ~3 years.
Outcome
• Alive without dementia: 56.3% vs 55.0% (NS).
• MOCA ordinal: OR 1.41 (0.98-1.96).
• WMH number: 49 vs 48 (NS).
• Recent subcortical infarct: 1.5% vs 1.2%.
• CMB number: 1 (0-3) vs 1 (0-3); CSS: 1 (1-1) vs 1.5 (1-2).
• MOCA ordinal: OR 1.41 (0.98-1.96).
• WMH number: 49 vs 48 (NS).
• Recent subcortical infarct: 1.5% vs 1.2%.
• CMB number: 1 (0-3) vs 1 (0-3); CSS: 1 (1-1) vs 1.5 (1-2).