OPTIMAL-Stroke

Presented in LBS.02 at AHA 2026 (Saturday 7 November, Gisele Sampaio Silva, Federal University of Sao Paulo) and published simultaneously in NEJM. OPTIMAL-Stroke randomised 4,368 adults (mean age 63.9, 47.9 percent women; 92 percent ischaemic stroke, 8 percent TIA; median 1.1 years after the event; systolic 130 to 180 mmHg, baseline 146.7/81.6) at 30 Brazilian sites between 2019 and 2022 to a systolic target below 120 or below 140 mmHg, open label with blinded adjudication. Achieved systolic pressure after the first 3 months: 122.0 versus 135.2 mmHg (difference 13.1), on 3.0 versus 2.2 drug classes. Over a median 3.9 years the primary endpoint (cardiovascular death, non-fatal MI, non-fatal stroke, hospitalisation for unstable angina or heart failure) occurred in 10.9 percent (236 of 2,172) versus 13.5 percent (297 of 2,196), HR 0.79 (0.67 to 0.94), P=0.007; 3.25 versus 4.11 per 100 patient-years. Stroke 4.7 versus 6.4 percent, HR 0.73 (0.56 to 0.94), driven by ischaemic stroke; cardiovascular death 4.6 versus 4.7 percent, HR 0.96; the broader composite with all-cause death 17.4 versus 20.2 percent, HR 0.84. Serious adverse events 15.1 versus 15.3 percent; renal composite 3.9 versus 2.2 percent, HR 1.76 (1.24 to 2.50), mostly sustained eGFR falls of 50 percent or more, long-term dialysis 6 versus 3 patients; hyponatraemia 3.3 versus 2.2 percent; injurious falls 1.0 versus 1.7 percent. Discussant Daichi Shimbo: NNT 38, NNH 59. The first dedicated outcomes trial of an intensive target after stroke supports aiming low with kidney monitoring.