Applied Evidence

Dual antiplatelet Tx for stroke prevention: Worth the risk?

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References

In efforts to gain insight on CLO-ASA’s use in a more diverse patient population, the POINT trial included almost 5000 patients, with 82% from the United States, who were randomized within 12 hours of symptom onset to CLO-ASA or aspirin monotherapy for 90 days.4 Similar to the CHANCE study, the POINT study included patients with mild ischemic strokes (NIHSS ≤ 3) or high-risk TIA (ABCD2 ≥ 4). Combination therapy significantly reduced the primary endpoint of ischemic stroke, myocardial infarction (MI), or death from an ischemic event. Contrary to CHANCE, there was a significant increase in major bleeding in those assigned to combination therapy, which resulted in the trial being stopped early.4

A closer look at safety differences. CHANCE and POINT were the first major trials to show a benefit of CLO-ASA for secondary prevention of stroke, yet their differences in safety outcomes, specifically major hemorrhage, argued for a deeper reconciliation of their results.4,5 While both trials initiated secondary prevention within 24 hours of symptom onset, the difference in duration of combination therapy (21 days in CHANCE vs 90 days in POINT) likely impacted the rates of hemorrhage. When results from POINT were stratified by time period, particularly within the first 30 days of therapy (similar to the 21-day treatment duration of CHANCE), combination therapy significantly reduced the primary endpoint of ischemic stroke, MI, or death from an ischemic event (3.9% CLO-ASA vs 5.8% aspirin; P = .02) without an increased risk for major hemorrhage. Between 30 and 90 days, this efficacy benefit disappeared. However, bleeding rates between groups continued to separate throughout the 90-day course. In this light, the 30-day outcomes of POINT are largely similar to CHANCE and support the short-term use of CLO-ASA for secondary prevention without an associated increase in major bleeding.4,5

Antiplatelet dosing in POINT and CHANCE may also play a role in the contrasting safety results between the trials.4,5 While both studies utilized clopidogrel loading doses, POINT used 600 mg while CHANCE used 300 mg. Clopidogrel maintenance dosing was the same at 75 mg/d. In CHANCE, aspirin dosing was protocolized to 75 mg/d; however, in POINT, 31% of patients used > 100 mg/d aspirin.4,5 It is possible that the higher doses of both aspirin and clopidogrel in the POINT trial contributed to the difference in the occurrence of major hemorrhage between the treatment groups in these trials.

The takeaway. Based on currently available data, patients who are best suited to benefit from CLO-ASA are those who have had minor noncardioembolic ischemic strokes or high-risk TIAs.4,5,11 Clopidogrel should be given as a 300-mg loading dose followed by 75 mg/d given concomitantly with aspirin at a dose no higher than 100 mg/d. CLO-ASA therapy should be initiated within 24 hours of symptom onset and be continued for no longer than 1 month, after which chronic preventive therapy with either aspirin or clopidogrel monotherapy should be started.4,5,11

Dipyridamole and aspirin: A controversial option

Since the approval of the combination product ASA-ERDP, there has been considerable controversy about using this combination over other therapies, such as aspirin or clopidogrel, for recurrent ischemic stroke prevention. Much of this controversy arises from limitations in the trial designs.

Continue to: The first trial to show benefit...

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