Source: Sandercock P, Counsell C, Tseng M, Cecconi E. Oral antiplatelet therapy for acute ischaemic stroke. Cochrane Database of Systematic Reviews 2014;(3):1-45.
Study Population: 41,483 adult patients presenting with acute stroke
Efficacy Endpoints: Death or dependence, recurrent stroke, complete recovery from stroke
Harm Endpoints: Symptomatic intracranial hemorrhage, major extracranial hemorrhage
Narrative: Annually in the United States, approximately 610,000 people have a stroke for the first time and 185,000 more have recurrent strokes. Of these 87% are ischemic,1 most often due to thrombosis or embolism and a subsequent lack of blood flow. In ischemic strokes, platelets become activated and release neurotoxic and thrombogenic molecules,2 making antiplatelet therapy logical. Potential harms include bleeding, especially within the brain. The goal of this summary is to provide updated evidence on the safety and efficacy of immediate oral antiplatelet therapy in patients presenting with acute ischemic stroke.3
This Cochrane systematic review identified eight randomized controlled trials involving 41,483 predominantly elderly adult patients with presumed acute ischemic stroke. No new studies were identified, however four studies from the 2008 review were excluded as they studied intravenous antiplatelet agents. Two studies, IST and CAST, accounted for 98% of the data.3 These two trials randomized patients to receive two weeks of 300 mg/day aspirin or no treatment (IST), and four weeks of 160 mg/day aspirin or placebo within 48 hours of presentation (CAST). The primary outcome was death or dependency at least one month after stroke (six months for IST and one month for CAST). Secondary outcomes, measured during the treatment period (two weeks for IST and four weeks for CAST), were recurrent stroke, intracranial hemorrhage, major extracranial hemorrhage, and complete recovery from the stroke.4, 5
Aspirin therapy was associated with a decreased risk of death or dependency (Odds Ratio [OR]: 0.95; 95% Confidence Interval (CI): 0.91 – 0.99; Absolute Risk Difference [ARD]: 1.3%; Number Needed to Treat [NNT]: 79), a decreased risk of recurrent stroke (OR: 0.77; 95% CI: 0.69 – 0.87; ARD: 0.7%; NNT: 140), and an increased likelihood of complete recovery (OR: 1.06; 95% CI: 1.01 – 1.11; ARD: 1.1%; NNT: 89). Aspirin therapy was also associated with an increased risk of symptomatic intracranial hemorrhage (OR: 1.23; 95% CI: 1.00 – 1.50; ARD: 0.2%; Number Needed to Harm (NNH): 574), and an increased risk of major extracranial hemorrhage (OR: 1.69; 95% CI: 1.35 – 2.11; ARD: 0.4%; NNH: 245).
Caveats: The quality of evidence was generally good and there was low heterogeneity. There are however several limitations to the data. First, in the CAST and IST trials respectively, 87% and 67% of patients did not have a CT scan before randomization.4, 5 Consequently, intracranial hemorrhages that were initially present may have been missed, reducing benefits and increasing harms. Since approximately 13% of strokes are hemorrhagic,1 it is quite likely this occurred. Second, in the large IST trial, patients and clinicians were not blinded which may have introduced bias. For example, clinicians may have been more likely to order CT scans for patients on treatment and thus may have identified more intracranial hemorrhages. The IST authors downplay these concerns by pointing out the results were similar to the CAST trial, which was blinded, and that most patients did not recall their treatment allocation at 6 months.4 A third limitation is that there was variability in the studies. For the IST and CAST trials, as mentioned above, the treatment duration, follow-up time and aspirin dose varied. Notably in the IST trial the primary outcome was determined based on six month follow up whereas in the CAST trial it was one month. Additionally, in several of the small studies representing less than 2% of the data, alternative antiplatelet drug regimens were used. Finally, this review is unable to demonstrate when exactly aspirin should be started. There was no difference found in patients that started aspirin between 0 – 24 hours from onset and 25 – 48 hours from onset. Likely, aspirin should be started as soon as possible after onset since in the first 24 hours intracranial hemorrhage is unlikely but recurrent ischemic stroke is relatively common.6
In summary, aspirin therapy given within 48 hours of acute ischemic stroke had a small but significant effect in reducing the risk of death, dependence, or recurrent stroke, and increased the chance of complete recovery, although it was associated with an increased risk of bleeding. Aspirin is a safe, inexpensive, easy to administer, and widely available drug. Based on the evidence of this systematic review we have chosen a Green rating (Benefits > Harms).
Author: John Conway, BS; Benjamin W. Friedman, MD
Supervising Editor: Shahriar Zehtabchi, MD
Published/Updated: February 14, 2020
The title bar is color-coded with our overall recommendation.