Rivaroxaban increased risk for cardiac events compared with warfarin among patients with high-risk antiphospholipid syndrome, according to results of a randomized, open-label, multicenter, noninferiority study published in Blood.
The analysis included patients with antiphospholipid syndrome who were high risk and triple positive for lupus anticoagulant, anticardiolipin and anti-2-glycoprotein I antibodies.
Patients with antiphospholipid syndrome who are triple positive are at the higher risk for a first thrombotic event, as well as at risk for a higher rate of recurrence despite antithrombotic treatment.
“Triple-positive individuals are less than 50% of those positive in one or two tests exploring the presence of antiphospholipid antibodies,” Vittorio Pengo, MD, associate professor of cardiology at University of Padova in Italy, and colleagues wrote. “Secondary prevention of thromboembolic events is the primary therapeutic goal in these patients and the mainstay treatment is warfarin, as it significantly reduces thromboembolic recurrences. However, the management of warfarin therapy is challenging, and thromboembolic events are frequent when the intensity of anticoagulation is not adequate.”
Researchers randomly assigned patients to rivaroxaban (n = 59; Xarelto, Janssen) or warfarin (n = 61) for the prevention of thromboembolic events, major bleeding and vascular death.
The trial was terminated prematurely after the enrollment of 120 patients because of an excess of events among patients assigned rivaroxaban.
Mean follow-up was 569 days.
Eleven patients (19%) in the rivaroxaban arm experienced events compared with two patients (3%) in the warfarin arm (HR = 6.7; 95% CI, 1.5-30.5).
Thromboembolic events occurred among seven patients (12%) randomly assigned rivaroxaban, including four patients with ischemic stroke and three patients with myocardial infarction. No thromboembolic events occurred among patients assigned warfarin.
“The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events as compared with warfarin, thus showing no benefit and excess risk,” the researchers wrote.
Major bleeding occurred among four patients (7%) in the rivaroxaban arm compared with two patients (3%) in the warfarin group (HR = 2.5; 95% CI, 0.5-13.6).
Researchers observed no deaths in the study population.
“The results of our trial should raise the awareness among health care personnel on the lack of efficacy of rivaroxaban in high-risk triple-positive antiphospholipid syndrome patients and may be relevant for the other trials testing direct anticoagulants in this setting,” the researcher wrote. “Results from this study cannot be translated to antiphospholipid syndrome patients without a ‘full positive’ laboratory profile. At present, the therapeutic strategy in patients with a laboratory profile different from that of this study should be considered on a case-by-case basis, taking into account the presence of additional risk factors for venous and arterial thrombosis, the nature of venous thromboembolism (provoked or unprovoked), and the risk of bleeding.” – by Cassie Homer
Disclosures: The researchers report no relevant financial disclosures.