ASPIRIN PROPHYLAXIS FOR ANTIPHOSPHOLIPID SYNDROME

NEW YORK (Reuters Health) Oct 22 - Adding warfarin to aspirin doesn't seem to improve thromboprophylaxis in patients with antiphospholipid antibodies (aPL), according to results from the ALIWAPAS study.

And warfarin increases the risk for bleeding, the researchers say.

"Patients with triple positivity (positive for anticardiolipin, anti-Beta2-GP1, and Lupus anticoagulant) seem to have the highest risk of developing a thrombotic event," Dr. Maria J. Cuadrado from St. Thomas' Hospital, London, UK told Reuters Health by email. "These types of patients should receive aspirin."

Dr. Cuadrado said warfarin should not be used for primary prevention: "Warfarin is used only after a thrombotic event."

Indeed, routine primary prevention of all aPL-positive patients remains controversial, Dr. Cuadrado added, noting that "several studies show that the rate of thrombosis is low in patients with low levels of antiphospholipid antibodies and in those with intermittent positivity."

Dr. Cuadrado and colleagues compared low-dose aspirin and low-dose aspirin plus warfarin in the primary prevention of thrombosis in 232 aPL-positive patients with systemic lupus erythematosus (SLE) and/or obstetric criteria for antiphospholipid syndrome.

One hundred sixty-six patients agreed to be randomly assigned to low-dose aspirin (LDA) or LDA plus warfarin (LDA+W). Sixty-six patients who declined randomization for fear they would be assigned to LDA+W and have to undergo monitoring were included as untreated controls.

The incidence of thrombotic events per 100 person-years was 1.7 in the LDA group, 1.8 in the LDA+W group, and 4.9 in the observational arm. None of these differences was statistically significant, according to a report online October 4th in Rheumatology.

Similarly, there was no difference in rates of thrombotic events between subgroups taking 75 mg or 100 mg of aspirin daily.

Eleven patients in the LDA+W group, but none in the LDA group, had minor bleeding episodes. During the three years of follow-up, there was one extra case of bleeding for every 7.6 patients treated with LDA+W.]

"Although this study did not have the power to detect a clinically important difference in efficacy between the treatment groups, we observed a clear difference in tolerability in favor of LDA alone," the researchers say. "Thus, LDA+W appears to be a poor, unattractive therapeutic approach for primary prevention of thrombosis in this population."

"Our study and others showed that most of the patients who suffered a thrombotic event did have other additional risk factors for thrombosis, namely, hypertension, hypercholesterolemia, surgery, and so on," Dr. Cuadrado said. "We encourage doctors to exhaustively control conventional risk factors for thrombosis and to make prophylaxis with low molecular weight heparin in prothrombotic situations such as surgery, long-haul flight, and immobilization."

Dr. Gabriela Hernandez-Molina from Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico has also studied risk factors for thrombosis in these patients. She told Reuters Health, "Regarding primary thromboprophylaxis, most physicians prescribe aspirin to asymptomatic patients (with or without SLE) with positive antiphospholipid antibodies. Nevertheless there is retrospective data and a randomized double-blind trial that showed no efficacy of this drug in the prevention of thrombosis. This information is hampered because of the inclusion or not of patients with different 'high' risk antiphospholipid profiles among studies."

"As recognized by the authors, the study did not have the power to detect a clinically important difference in efficacy," Dr. Hernandez-Molina said. "Thus, results should be interpreted with caution. I think the study of primary thromboprophylaxis in antiphospholipid syndrome patients is still open."