Weekly journal scan: it takes two for acute stroke

Key points• INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis) was a double-blind, randomized, placebo-controlled, two-by-two factorial trial among patients with mild ischaemic stroke or high-risk transient ischaemic attack (TIA), presumably caused by atherosclerosis, based on imaging criteria. 1It tested the hypothesis that dual antiplatelet therapy (DAPT) with clopidogrel and low-dose aspirin initiated within 72 h after the onset of symptoms would be superior to aspirin alone with regard to the risk of new ischaemic or haemorrhagic stroke.• The trial, funded by the National Natural Science Foundation of China and others, enrolled 6100 patients 35-80 years of age, who presented for the most part with mild ischaemic stroke [National Institutes of Health Stroke Scale (NIHSS) score of ≤5; with higher scores indicating more severe stroke], and had not undergone thrombolysis or thrombectomy.Patients (median age, 65 years; 36% women, and 98.5% Han Chinese) were randomly assigned to receive clopidogrel (300 mg on Day 1 and 75 mg daily on Days 2-90) plus aspirin (100-300 mg on Day 1 and 100 mg daily on Days 2-21) or matching clopidogrel placebo plus aspirin (100-300 mg on Day 1 and 100 mg daily on Days 2-90).A total of 13% of the patients were randomized no more than 24 h after stroke onset, and 87% were assigned after 24 h and no more than 72 h after onset.• The primary efficacy endpoint was new stroke (ischaemic or haemorrhagic), and the primary safety outcome was moderate-to-severe bleeding [as defined according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial] within 90 days.A new stroke occurred in 222 patients (7.3%) in the DAPT group and in 279 patients (9.2%) in the aspirin group [hazard ratio (HR), 0.79; 95% CI, 0.66-0.94;P = .008;number-needed-to-treat to prevent one additional stroke, 53].This net result reflected the occurrence of 66 fewer ischaemic strokes and 10 more haemorrhagic strokes in the DAPT group than in the aspirin group.There was no trend for efficacy being related to the variable delay from stroke onset or to the severity of the qualifying stroke.Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the DAPT group and in 13 patients (0.4%) in the aspirin group (HR, 2.08; 95% CI, 1.07-4.04;P = .03;number-needed-to-harm to cause one additional bleeding event, 200).