Shashank Shekhar, MD, MS
Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018
The long-anticipated POINT trial has recently been presented at the 4th European Stroke Organization Conference 2018, and subsequently published in NEJM, in May 2018. After the CHANCE trial, many centers started using dual antiplatelet for lacunar strokes and TIA; there remained uncertainty over the validity of the non-Chinese population. The POINT trial results add validity to the five-years-old questions since the CHANCE trial.
The POINT trail is a multinational, randomized, placebo-controlled trial. The patients were assigned in 1:1 ratio between treatment and control arm. The treatment arm in the trial received a loading dose of 600mg Clopidogrel, followed by daily 75mg with daily aspirin (50mg-325mg). The control arm received same range of daily Aspirin with Placebo. The trial enrolled 4881 patients at 269 international sites in 10 different countries.
The primary outcome was a composite risk of ischemic stroke, myocardial infarction or death from ischemic stroke. The safety outcome was symptomatic intracranial hemorrhage, intraocular bleed resulting in vision loss, transfusion of 2 or more units of RBC or whole blood, hospitalization or death due to hemorrhage. The trial was designed to have a power of 90% to detect a hazard ratio of 0.75.
The results suggested better primary outcome in the treatment arm than placebo. See Figure 1 for overall results. The secondary outcome (ischemic stroke) was lower in the Clopidogrel group vs. the aspirin-only group. The overall risk of ischemic or hemorrhagic stroke was lower in the treatment arm (dual antiplatelet) vs. aspirin alone (HR 0.74; 95% CI, 0.58-0.94; P=0.01). The primary safely outcome showed more major hemorrhage in the treatment arm (HR 2.32; 95% CI 1.10-4.87); P=0.02).
The POINT trial is more racially generalizable than the CHANCE trial. The overall benefit of dual antiplatelet is obvious during the first week with lower bleeding risks. However, beyond one month, the bleeding complications appeared to have a linear relation to time, suggesting that dual antiplatelet is better when administered up to 3-4 weeks, a finding similar to the CHANCE trial. In practical terms, short treatment course would result in better compliance, and lesser hazard (bleeding risk) amongst stroke patients who either do not get a follow-up appointment in the first three months or lose to follow-ups.
Even though two large trials now suggest better efficacy with dual antiplanet <3-4 weeks of treatment in patients with mild stroke or TIA, the treating physicians or vascular neurologist should not generalize the dual antiplatelet on all patients and should take extra care in patients with cerebral microbleed or other hemorrhagic risks.