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DAPT may offer greatest benefit 21 days after minor stroke, TIA
The benefit of dual antiplatelet therapy after high-risk transient ischemic attack or minor ischemic stroke was limited to the first 21 days after the event, according to a pooled analysis of the CHANCE and POINT trials published in JAMA Neurology.
“It’s important to remind people that the benefits of clopidogrel-aspirin far exceed the excess risks of hemorrhage in the few weeks after a minor stroke or TIA,” S. Claiborne Johnston, MD, PhD, dean, vice president for medical affairs and Frank and Charmaine Denius Distinguished Dean’s Chair at The University of Texas at Austin Dell Medical School, told Healio. “Concern about hemorrhage should rarely alter the decision to treat, but may impact a recommendation on duration.”
CHANCE and POINT trials
Yuesong Pan, PhD, of the department of neurology at Beijing Tiantan Hospital at Capital Medical University, and colleagues analyzed data from 5,170 patients from the CHANCE trial and 4,881 patients from the POINT trial who were assigned either clopidogrel with aspirin or aspirin alone after a minor stroke or high-risk TIA. Of the 10,051 patients (median age, 63 years; 61% men), 5,016 were assigned clopidogrel and aspirin and 5,035 were assigned aspirin alone.
Patients from the CHANCE trial were treated with DAPT for 21 days then aspirin alone from 22 to 90 days, whereas those in the POINT trial were treated with DAPT for 90 days.
The primary efficacy outcome was a new major ischemic event at 90 days, which included MI, ischemic stroke or death from ischemic vascular causes. The secondary efficacy endpoints were a composite of primary efficacy outcome and major hemorrhagic and stroke, in addition to each component of the primary efficacy endpoint. The primary safety outcome was defined as major hemorrhage at 90 days. The secondary safety outcomes were minor hemorrhage, hemorrhagic stroke, all-cause death and major or minor hemorrhage.
At 90 days, patients assigned clopidogrel and aspirin had a reduction in the risk for major ischemic events vs. those assigned aspirin alone (6.5% vs. 9.1%; HR = 0.7; 95% CI, 0.61-0.81). This reduction was mainly seen within the first 21 days of treatment (5.2% vs. 7.8%; HR = 0.66; 95% CI, 0.56-0.77), but not between 22 and 90 days.
“We believe that 21 days just makes more sense than 90 days based on these data,” Johnston said in an interview. “I know others are likely to agree, and I suspect guidelines will follow suit.”
Heterogeneity of treatment outcome was not seen across both trials and prespecified subgroups.
Major hemorrhages
More patients assigned clopidogrel and aspirin had major hemorrhages compared with those assigned aspirin alone, although it was not significant (0.6% vs. 0.4%; adjusted HR = 1.59; 95% CI, 0.88-2.86).
“The findings suggest that DAPT may be optimally reserved for the first 21 days after an ischemic stroke or high-risk TIA,” Johnston told Healio. “While derived from randomized trials, this is a secondary analysis and so not the same level of quality. Still, it’s very unlikely we’ll see higher-quality data on the question of duration of therapy.” – by Darlene Dobkowski
For more information:
S. Claiborne Johnston, MD, PhD, can be reached at Dean’s Office, Dell Medical School, University of Texas at Austin, 1912 Speedway, Suite 564, Austin, TX 78712; email: clay.johnston@utexas.edu; Twitter: @claydellmed.
Disclosures: The study was supported by a grant from Sanofi. Johnston reports he received grants from AstraZeneca and the NIH/National Institute of Neurological Disorders and Stroke, drug and matching placebo for 85% of patients from Sanofi and nonfinancial support from Sanofi. Pan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.