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Comparing Apixaban to Warfarin for Reducing Stroke Risk in Thrombotic Antiphospholipid Syndrome

December 6, 2021

December 2021

No

Compared with warfarin, apixaban did not prevent the risk of recurrent thrombosis in patients with thrombotic antiphospholipid syndrome, according to findings published in Blood Advances.

“This study is the first prospective randomized controlled trial comparing apixaban and warfarin among patients with thrombotic antiphospholipid syndrome receiving long-term anticoagulation for the outcome of recurrent thrombosis prevention,” lead study author Scott Woller, MD, of the University of Utah School of Medicine, told ASH Clinical News. “Our observations raise the concern that apixaban is not an equitable substitute for warfarin to prevent recurrent thrombosis in patients with thrombotic antiphospholipid syndrome.”

The multicenter, open-label trial included 48 patients with thrombotic antiphospholipid syndrome who were receiving therapeutic anticoagulation for secondary prevention of thrombosis for six months or longer. At the start of the study, participants were randomly assigned to either apixaban 2.5 mg twice per day (n=23) or warfarin with a target international normalized ratio (INR) of 2-3 (n=25) for a total of 12 months. Clinically overt thrombosis and vascular death comprised the primary efficacy outcome.

Changes were made to the protocol during the study following recommendations set forth by the data safety monitoring board. Specifically, the dose of apixaban was increased to 5 mg twice daily after the 25th patient was randomized. Additionally, patients with a history of arterial thrombosis were excluded from enrollment after the 30th patient was randomized.

The average age of the overall study cohort was 47.3 years, and ages were comparable across the apixaban and warfarin arms (46 vs. 48.5 years, respectively). Approximately 87% of patients in the apixaban group and 76% of patients in the warfarin group were never smokers.

Identified risk factors for stroke in the overall population at baseline included smoking (20.8%), hypertension (14.6%), diabetes (16.7%), dyslipidemia (16.7%), and heritable thrombophilia (39.6%). The most used concomitant medications included vitamin D (37.5%) and calcium (33.3%) supplements.

Adherence to apixaban was high (97.3%). In the warfarin arm, the percent time in therapeutic rage was recorded at 60% (standard deviation = 23.8%). The researchers reported that there was no convergence of the Cox proportional-hazards models, limiting the reporting of comparisons of outcomes between arms and their statistical significance.
A total of six thrombotic events (all strokes) were recorded in patients who received apixaban (318 events per 1,000 person-years), according to the intention-to-treat analysis of the primary efficacy endpoint. No patients in the warfarin group had a thrombotic event during the study period. One major bleeding event (vaginal bleeding; INR=2.9) occurred in the warfarin group, but no clinically relevant non-major bleeding (CRNMB) events were reported, leading to an overall event rate of 40 per 1,000 person-years. In contrast, no major bleed or CRNMB occurred in the apixaban group.

In an analysis that combined the primary efficacy endpoints of thrombosis and vascular death, as well as the safety endpoints of major bleeding and CRNMB, the investigators found that rates of adverse outcomes per 1,000 person years were 318 for apixaban and 40 for warfarin.

Three thrombotic events occurred in each of the dosing groups, according to the as-treated analysis. The respective 1,000 person-year rates for thrombotic events in the apixaban 2.5 mg and 5 mg dosing groups were 603 and 231 events. In addition, there were no major bleeding and CRNMB events with apixaban and 34 per 1,000 person-years with warfarin.
The authors wrote that these results remain consistent with data supporting the role of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome. “[Our findings] suggest that apixaban may not be an effective alternative to warfarin among patients with [the disorder].”

Study authors report relationships with Bristol Myers Squibb and Pfizer, which funded the study.

Reference

Woller SC, Stevens SM, Kaplan D, et al. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: A randomized trial [published online ahead of print, 2021 Oct 18]. Blood Adv. doi: 10.1182/bloodadvances.2021005808.

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