Study: Aspirin had no effect on stroke, thromboembolism risk in AF patients

Issue: November 10, 2011

Thromboprophylaxis with vitamin K antagonists reduced the risks for stroke and thromboembolism in patients with non-valvular atrial fibrillation, while acetylsalicylic acid treatment had no effect, according to new data from a large cohort registry study.

However, researchers found that the risk for bleeding was increased with both vitamin K antagonists and acetylsalicylic acid.

“As far as we are aware, this is the largest ‘real-world’ cohort study using a nationwide cohort of patients with non-valvular AF, which confirms that thromboprophylaxis with vitamin K antagonists significantly reduced the risk for thromboembolism compared to acetylsalicylic acid and no treatment,” researchers from Denmark and the U.K. wrote in the journal Thrombosis and Haemostasis.

From 1997 to 2008, more than 132,000 patients with non-valvular AF were identified using Denmark’s National Patient Registry. Researchers used CHADS₂ and CHA₂DS₂-VASc scores to assess thromboembolic risk and HAS-BLED score to assess bleeding risk for patients. Follow-up treatment with vitamin K antagonists and acetylsalicylic acid was started 7 days after hospitalization discharge.

Risk for thromboembolism was higher for patients taking acetylsalicylic acid (HR=1.81; 95% CI, 1.73-1.90), vitamin K antagonists combined with acetylsalicylic acid (HR=1.14; 95% CI, 1.06-1.23) and no treatment (HR=1.86; 95% CI, 1.78-1.95) when compared with patients taking vitamin K antagonists alone. In contrast, bleeding risk increased with vitamin K antagonist treatment (HR=1.0), acetylsalicylic acid treatment (HR=0.93) and vitamin K antagonist plus acetylsalicylic acid treatment (HR=1.64) compared with no treatment (HR=0.84), according to study results.

During the study period, 38.5% of patients changed treatments or had a minimum 1 day off treatment, according to researchers. At 1-year follow-up, treatment with vitamin K antagonists lowered thromboembolism risk in patients with CHADS2 or CHA₂DS₂-VASc score of 1 or greater vs. acetylsalicylic acid or no treatment. At 12-year follow-up, treatment with vitamin K antagonists alone or in combination with acetylsalicylic acid decreased thromboembolism risk vs. no treatment or acetylsalicylic acid alone. According to the researchers, risk for thromboembolism was not decreased with acetylsalicylic acid alone vs. no treatment, even when patients had a high bleeding risk (HAS-BLED >3) or vascular disease. Overall, high-risk patients treated with vitamin K antagonists had the lowest bleeding risk, according to CHADS₂score, and CHA₂DS₂-VASc score showed acetylsalicylic acidwas associated with a higher bleeding risk. Vitamin K antagonists also were associated with a neutral or positive net clinical benefit in patients with CHADS₂ score of 0 or greater and CHA₂DS₂-VASc score of 1 or greater.

Patients receiving acetylsalicylic acid generally were older, and those treated with acetylsalicylic acid alone or in combination with vitamin K antagonists had a higher prevalence of previous thromboembolism and higher CHADS₂, CHA₂DS₂-VASc and HAS-BLED scores. Patients receiving vitamin K antagonists alone tended to have less vascular disease; those treated with vitamin K antagonists alone or in combination with acetylsalicylic acid had less previous bleeds and were more likely to be men, according to the results. – by Casey Murphy

For more information:

Olesen JB. Thromb Haemost. 2011;106:739-749.

Disclosures: The researchers report no relevant financial disclosures.

This very large cohort study across an entire country strongly supports the use of vitamin K antagonists (warfarin-like drugs) for stroke prophylaxis. Although that is not really news, the most impressive finding was that aspirin showed absolutely no efficacy, but did increase bleeding risk. The take-home message is that use of aspirin to prevent stroke in patients with AF remains very poorly justified; it may make a doctor or patient feel like something is being done, but the data belie that assumption. Of course, patients with other indications for aspirin should continue to receive it.

– Dan Roden, MD

Professor of Medicine and Pharmacology and William Stokes Professor of Experimental Therapeutics at Vanderbilt University; Director of the Oates Institute for Experimental Therapeutics and Assistant Vice-Chancellor for Personalized Medicine.

Disclosures: Dr. Roden has received royalty fees on a patent designed to identify patients at risk for drug-induced arrhythmia, and consulting fees from Merck, Astellas and Sanofi.