Oral Anticoagulants Trump Antiplatelet Therapy for Primary Stroke Prevention in Nonvalvular AF

August 6, 2007 — Oral anticoagulants are superior to antiplatelet therapy for primary stroke prevention in patients with nonvalvular atrial fibrillation (AF), according to a new report published in the Cochrane Database of Systematic Reviews July 18.
The meta-analysis, which included 8 randomized controlled trials and almost 10,000 patients, found warfarin and other anticoagulants reduced primary stroke risk in patients with AF by about 33% compared with antiplatelet therapies. Patients who received antiplatelet therapy had a 20% reduction in primary stroke risk compared with their counterparts who received no preventive treatment.
"When it comes to secondary stroke prevention, it's well-known warfarin is superior to aspirin or other antiplatelet therapy, but we wanted to compare the efficacy of these agents in primary prevention. We found warfarin or other anticoagulant therapy reduced the risk of stroke and other ischemic vascular events in patients with nonvalvular AF and that this effect was superior to the effect of antiplatelet therapy in this patient population," study investigator Maria Aguilar, MD, from the Mayo Clinic in Scottsdale, Arizona, told Medscape.
"Anticoagulants reduced [stroke] risk 10% to 20% more than antiplatelet therapy, including aspirin, clopidogrel, and other antiplatelet agents. Based on these results, we think warfarin is probably the best option for primary stroke prevention in patients who can take it safely," she added.
For the review, the investigators included all unconfounded, randomized trials in which long-term (more than 4 weeks), adjusted-dose oral anticoagulant treatment was compared with antiplatelet therapy in patients with chronic nonvalvular AF.
Management Challenges
The 8 trials included 9598 patients without prior stroke or transient ischemic attack (TIA) and looked at warfarin vs adjusted-dose aspirin (in doses ranging from 75 to 325 mg/day). The mean overall follow-up was 1.9 years per study participant.
Oral anticoagulants were associated with lower risk of all stroke, ischemic stroke, and systemic emboli. In addition, the authors report that all disabling or fatal strokes and myocardial infarction (MI) were substantially, but not significantly, reduced by oral anticoagulants.
Vascular death and all-cause mortality outcomes were similar between the 2 treatments; intracranial hemorrhage was increased by anticoagulant therapy.
While the study's results are not unexpected, said Dr. Aguilar, she hopes that the findings will help strengthen physicians' confidence in the benefits of anticoagulant therapy in this patient group.
Admittedly, said Dr. Aguilar, warfarin is not a benign agent and can cause devastating complications, including death. In addition, there are significant challenges associated with its management.
"Treating patients with warfarin requires an anticoagulation clinic, access to a lab, and a significant commitment from the patient and the patient's family. As a result, most general practitioners favor antiplatelet therapy," she said.
Only Available Option
Nevertheless, she added, at this point it is the only available option for stroke prevention in this patient group and, when administered correctly, is safe and effective.
"I hope these results will help clinicians who are still reluctant to use anticoagulation therapy take a more open-minded approach toward it," she said.
What is needed ultimately, she said, is an agent that combines the efficacy of warfarin with the safety of aspirin. The best recent hope for this was ximelagatran.
The one-size-fits-all drug promised to overcome the monitoring, drug interaction, and dietary issues associated with warfarin therapy. Unfortunately, said Dr. Aguilar, the agent turned out to be hepatotoxic and never made it to market.
"At this point, there are no new therapies in the pipeline to prevent stroke in this growing population of older patients with nonvalvular atrial fibrillation. We will have to learn to live with what we have and do our best to prevent stroke using existing antithrombotic therapy," she said.
Cochrane Database Syst Rev. Published online July 18, 2007.