World Stroke Congress
October 17-20, 2018

Danielle de Sa Boasquevisque, MD

Following a Transient Ischemic Attack (TIA) or minor ischemic stroke, the risk of having another ischemic stroke or vascular events within the next three months is 10-20%. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial was a randomized, double-blind study designed to evaluate the benefit of dual antiplatelet therapy (DAPT) compared to aspirin alone during the first 90 days after a minor ischemic stroke or transient ischemic attack. The primary efficacy outcome was major ischemic events, and the primary safety outcome was major hemorrhage.

The POINT Trial was halted after 84% of the anticipated number of participants had been enrolled. They found that patients enrolled in 3 months of DAPT had fewer major ischemic events than patients given aspirin alone (5% versus 6.5%, respectively; hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; p=0.02). However, the DAPT also seemed to increase chances of major hemorrhage compared to the aspirin controls (0.9% versus 0.4%, respectively; hazard ratio 2.32; 95% CI, 1.10-4.87; p=0.02).

A secondary analysis of POINT Trial data was presented by Jordan J. Elm at the World Stroke Congress in October in Montreal. It aimed to identify the time course of risks versus benefits of clopidogrel and aspirin in acute minor ischemic stroke and high-risk TIA patients and determine if there is an optimal time when patients would benefit most from using both aspirin and clopidogrel.

Analysis of the number of ischemic events per week showed that major ischemic events occurred mainly in the first week. Because group hazard ratios vary during the 90 days, the time course for major ischemic events was also modelled using a piecewise proportional hazard model. The optimal cut point for preventing major ischemic events was 21 days favouring the DAPT group when compared to aspirin alone (3.6% versus 5.6%, respectively; hazard ratio 0.65; 95%CI, 0.50-0.85; p=0.0015). In this period, major hemorrhage occurred in 0.4% in the DAPT group and 0.2% in the aspirin group.

Beyond the 21-day period, the difference in proportion of major ischemic events between groups (1.4% versus 0.9%, respectively; hazard ratio 1.38; 95%CI, 0.81-2.35; p=0.24) compared to major hemorrhage (0.5% in the DAPT group versus 0.2% in the aspirin alone group) between both groups did not favour the dual antiplatelet group.

An examination of the cumulative probability across the 21 days following TIA or stroke onset revealed that risk of major ischemic event of both groups diverges after 12 hours, with higher probability of ischemic events in the aspirin alone group. They continue to diverge until 72 hours post-event, at which point the group difference levels out. The POINT Trial randomized patients within 12 hours of symptoms onset. Time course secondary analysis suggests that patients could benefit from starting dual antiplatelet therapy earlier, but beyond 12 hours, though, it was not tested in this trial.

Those results are in line with the Clopidogrel in High-risk Patient With Acute Non-disabling Cerebrovascular Events (CHANCE) Trial, a similar study that tested the benefit of clopidogrel and aspirin versus aspirin in a Chinese population and showed similar benefit using dual antiplatelet therapy within 21 days. One major difference between the two studies is that the CHANCE trial did not show increased risk of hemorrhage in the dual antiplatelet group.

Dr. Elm concluded at the World Stroke Congress that clopidogrel and aspirin use may best be limited to 21 days post-ischemic attack to maximize benefit and reduce risk.