Low rates of bleeding with both aspirin plus clopidogrel and aspirin alone after TIA or minor stroke

Reference

Tillman H, Johnston SC, Farrant M, et al. Risk for major hemorrhages in patients receiving clopidogrel and aspirin compared with aspirin alone after transient ischemic attack or minor ischemic stroke: a secondary analysis of the POINT randomized clinical trial. JAMA Neurol 2019;76(7):774-782.

Synopsis

This is a secondary analysis of a double-blind randomized trial comparing aspirin plus clopidogrel with aspirin alone in patients with a recent TIA or minor stroke. The original trial randomized 4819 patients within 12 hours of symptoms and followed up for 90 days. The study took place in 10 countries and 269 sites, hence the aspirin dosing reflected what is used in those countries (50 mg to 300 mg daily), while the clopidogrel or its placebo was given as a 600-mg loading dose on the first day and then 75 mg daily thereafter. The researcher evaluated the rate of bleeding based on the actual treatment received. They defined minor bleeding as bleeding that caused discontinuation of the study drug but not classifiable as "major." They used the following categories to classify events as major bleeding: nontraumatic, symptomatic intracranial hemorrhage; intraocular bleeding causing loss of vision: transfusion of 2 or more units of red blood cells or an equivalent amount of whole blood; hospitalization or prolongation of an existing hospitalization; or death. Fifty-one patients (2.1%) had minor bleeding: 1.6% using dual therapy and 0.5% using aspirin alone (number needed to treat to harm [NNTH] = 96; 95% CI 60 - 211). Thirty-three patients (0.7%) had at least one major hemorrhage: 0.9% in patients taking dual therapy and 0.2% taking aspirin alone (NNTH = 160; 91 - 482). Only 4 patients died. We reviewed the primary report (www.essentialevidenceplus.com/content/poem/200911) and there was no difference in the likelihood of the composite outcome of ischemic stroke, myocardial infarction, or ischemic vascular death between groups. Although the composite outcome was less common with clopidogrel plus aspirin, this was due to a reduction in ischemic stroke only (4.6% for dual therapy vs 6.3% for aspirin; number needed to treat = 59).