By Matthew E. Fink, MD

Louis and Gertrude Feil Professor and Chair, Department of Neurology; Associate Dean for Clinical Affairs, NYP/Weill Cornell Medical College

Dr. Fink reports no financial relationships relevant to this field of study.

SOURCE: 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;76:774-782.

The POINT trial showed a 25% reduction in the composite outcome of ischemic stroke, myocardial infarction, or ischemic vascular death in patients treated with clopidogrel plus aspirin for 90 days immediately following a transient ischemic attack (TIA) or minor acute ischemic stroke. Although there is recognition that combination therapy carries a higher risk of serious bleeding, this group was thought to be at low risk for intracerebral hemorrhage because only a small area of the brain was at risk from minor ischemic syndromes. These investigators have provided a secondary analysis reporting on the right rate and types of major hemorrhages that occurred in this cohort. The two groups consisted of patients treated within 12 hours of symptom onset, with either aspirin alone, 50-325 mg per day, or clopidogrel, 600 mg loading dose on day 1 followed by 75 mg daily for days 2-90. All minor and major hemorrhages were identified and recorded. The study included 269 sites worldwide that randomized 4,881 patients, at a median age of 65 years, with 45% women. Major hemorrhages occurred in 21 patients receiving clopidogrel plus aspirin and six patients in the aspirin-alone group. Four patients died from hemorrhages, three in the clopidogrel group and one in the aspirin group, and three of the four fatalities were from intracranial hemorrhage. Overall, there were seven intracranial hemorrhages, five in the clopidogrel group and two in the aspirin group. However, the most common location for major hemorrhages was in the gastrointestinal tract.

The risk of major hemorrhages was low in both groups, although treatment with clopidogrel and aspirin together increased the risk of major hemorrhages over aspirin alone from 0.2% to 0.9%. Caution should be taken and close observation of patients maintained when treating with dual antiplatelet therapies.