Aspirin for primary thrombosis prevention in the antiphospholipid syndrome

A randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody–positive individuals

Erkan, Doruk
Harrison, Melanie J.
Levy, Roger
Peterson, Margaret
Petri, Michelle
Sammaritano, Lisa
Unalp-Arida, Aynur
Vilela, Veronica
Yazici, Yusuf
Lockshin, Michael D.

¹Doruk Erkan, MD, Melanie J. Harrison, MD, MS, Margaret Peterson, PhD, Lisa Sammaritano, MD, Michael D. Lockshin, MD: Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York; ²Roger Levy, MD, Veronica Vilela, MD:Hospital Universitario Pedro Ernesto, Rio de Janeiro, Brazil; Michelle Petri, MD, MPH:Johns Hopkins University School of Medicine, Baltimore, Maryland; ⁴Aynur Unalp-Arida, MD, PhD: Johns Hopkins University School of Public Health, Baltimore, Maryland; ⁵Yusuf Yazici, MD:Long Island College Hospital, Brooklyn, and Hospital for Joint Diseases, New York, New York.

Address correspondence and reprint requests to Doruk Erkan, Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 E-mail: [email protected]

Supported by the New York Chapter of the Arthritis Foundation, and the New York Community Trust.

Submitted for publication November 11, 2006; accepted in revised form March 22, 2007

Arthritis & Rheumatism 56(7):p 2382-2391, July 2007.

Objective

To determine the efficacy of a daily dose of 81 mg aspirin in primary thrombosis prevention in asymptomatic, persistently antiphospholipid antibody (aPL)–positive individuals (those with positive aPL but no vascular and/or pregnancy events).

Methods

The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a multicenter, randomized, double-blind, placebo-controlled clinical trial in which asymptomatic, persistently aPL-positive individuals were randomized to receive a daily dose of 81 mg of aspirin or placebo. In a separate observational and parallel study, asymptomatic, persistently aPL-positive individuals who were taking aspirin or declined randomization were followed up prospectively.

Results

In the APLASA study, 98 individuals were randomized to receive aspirin or placebo (mean ± SD followup period 2.30 ± 0.95 years), of whom 48 received aspirin and 50 received placebo. In the observational study, 74 nonrandomized individuals were followed up prospectively (mean ± SD followup period 2.46 ± 0.76 years); 61 received aspirin and 13 did not. In the APLASA study, the acute thrombosis incidence rates were 2.75 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for the placebo-treated subjects (hazard ratio 1.04, 95% confidence interval 0.69–1.56) (P = 0.83). Similarly, in the observational study, the acute thrombosis incidence rates were 2.70 per 100 patient-years for aspirin-treated subjects and 0 per 100 patient-years for those not treated with aspirin. All but 1 patient with thrombosis in either study had concomitant thrombosis risk factors and/or systemic autoimmune disease at the time of thrombosis.

Conclusion

Our results suggest that asymptomatic, persistently aPL-positive individuals do not benefit from low-dose aspirin for primary thrombosis prophylaxis, have a low overall annual incidence rate of acute thrombosis, and develop vascular events when additional thrombosis risk factors are present.