MONTREAL—The optimal length for dual antiplatelet therapy (DAPT) in patients with mild stroke or transient ischemic attack (TIA) is 21 days, according to a prespecified analysis of data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial that was presented at the 11th World Stroke Congress. This duration of combined treatment maximizes protection against major ischemic events while minimizing the extra risk of a major hemorrhage, the researchers said.
Clopidogrel Plus Aspirin or Aspirin Alone
The POINT trial randomized 4,881 patients with a recent mild stroke or TIA and without atrial fibrillation to treatment with either clopidogrel plus aspirin or aspirin alone for 90 days. Compared with aspirin alone, DAPT decreased the incidence of a major ischemic event by 25% and more than doubled the rate of major hemorrhage.
The new prespecified analysis looked at outcomes on a weekly basis during 90 days of treatment. During the first 21 days, the rate of major hemorrhage events was 5.6% among those patients on aspirin alone and 3.6% among those on DAPT. Thus, DAPT was associated with a statistically significant 35% decrease in these adverse outcomes, said Jordan J. Elm, PhD, Associate Professor of Biostatistics at the Medical University of South Carolina in Charleston. During the subsequent 69 days of treatment, the incidence of major ischemic events was approximately 1% in both arms of the study, showing that after three weeks, the incremental benefit of DAPT disappeared, said Dr. Elm.
In contrast, the doubled rate of major hemorrhages (which mostly were reversible gastrointestinal bleeds) with DAPT, compared with aspirin alone, occurred at a relatively uniform rate throughout the 90 days of treatment. This suggests that limiting DAPT to 21 days could prevent many of the excess hemorrhages, maximize benefit, and reduce risk, said Dr. Elm. The findings of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial confirmed the efficacy of 21 days of DAPT following a minor stroke or TIA.
Although the new finding from the POINT study resulted from a secondary analysis, it should be taken into account when writing treatment guidelines, said Dr. Elm. “This is an important analysis that is not just hypothesis-generating.”
Another finding from the new analysis was that many major ischemic events, hence many of the events prevented by DAPT, occurred during the first two days following the index event. The POINT investigators were able to observe this finding because they enrolled patients and started treatment within 12 hours of the qualifying events.
“It is better to start treatment early,” said Dr. Elm. Major ischemic events continued to accumulate during Days 3 through 21, suggesting that patients could still benefit from DAPT if treatment did not start until 24 or 48 hours after the index event.
—Mitchel L. Zoler
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Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19.