Written by Peter Liu
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The WARSS trial found aspirin (325 mg daily) as effective as warfarin (INR 1.4-2.8) for the secondary prevention of noncardioembolic stroke, with fewer bleeding events, establishing aspirin as first-line therapy.
All’s fair in love and WARSS
The benefit of aspirin for secondary stroke prevention is now well-established, in part due to trials such as WARSS. This multicenter, double-blind, randomized trial compared warfarin (INR 1.4–2.8) to aspirin (325 mg daily) in preventing recurrent ischemic stroke or death in 2,206 patients with prior noncardioembolic stroke. At two years, no significant difference was observed in the primary outcome (warfarin 17.8% vs. aspirin 16.0%; HR 1.13, 95% CI 0.92–1.38, p=0.25). More patients on warfarin had major hemorrhage events (2.2 vs. 1.49 events per 100 patient-years; p=0.10) and minor hemorrhage events (20.8 vs. 12.9 events per 100 patient-years; p<0.001). These results established aspirin as an effective preventive medication without a clearly superior alternative at the time.
Today, there are several differences between current practice patterns and those from WARSS. First, aspirin 81mg is regarded by many to be as effective as 325mg with less bleeding, so many providers prefer this dosage. Second, most INR goals are higher than the INRs achieved in WARSS, though there has not been substantial evidence that higher INR goals significantly improve stroke-prevention treatment in noncardioembolic cases. Finally, there are many newer studies which support P2Y12 inhibitors, concomitant aspirin and dipyridamole, or aspirin with low-dose rivaroxaban as superior treatment regimens to aspirin for secondary stroke prevention. Nonetheless, due to findings from trials such as WARSS, aspirin remains the most commonly prescribed preventive medication for noncardioembolic stroke to date.
How does this change my practice?
Generally, my own practice has been to prescribe low-dose aspirin (81mg daily) as early as possible after a noncardioembolic stroke for secondary stroke prevention. It is satisfying to know about WARSS, a landmark trial that supports this decision. It is also important to know that more modern and efficacious treatments are now available that surpass aspirin monotherapy in efficacy, which include P2Y12 inhibitor monotherapy, concomitant aspirin and dipyridamole therapy, or aspirin with low-dose rivaroxaban.
Source
Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001 Nov 15;345(20):1444-51. doi: 10.1056/NEJMoa011258. PMID: 11794192
