“Results were not as expected,” Dr. Cervera said. No significant difference was found in the number of thromboses between groups, but patients on combination therapy had more episodes of bleeding.
“At this time, I recommend low-dose aspirin for primary thromboprophylaxis,” Dr. Cervera said. “Should a patient have an aspirin allergy, low molecular weight heparin [LMWH] should be considered for high-risk individuals. Smoking and sedentarism should be avoided, and hypertension and hyperlipidemia effectively controlled. Hydroxychloroquine should also be used for clot prevention in SLE [because] studies show a protective benefit.”5
The EULAR recommendations for the management of APS vary based on the patient’s aPL profile, history of thrombosis or obstetric complication, coexistence of other systemic autoimmune diseases & the presence of traditional cardiovascular risk factors.
Secondary Thromboprophylaxis
In 1995, a landmark trial demonstrated the benefit of warfarin with a goal INR of 3 to 4 for secondary prevention of venous clots in APS.6 Thereafter, similar benefit was confirmed for the currently recommended INR target of 2 to 3, though a higher target may be appropriate for certain patients.7
When it comes to arterial clots, the situation may be different. The Euro-Phospholipid Project followed 1,000 patients with APS over 10 years. With the implementation of warfarin, the incidence of venous thrombosis declined over time, but there was still an excess of arterial thrombosis at the 10-year mark.8
“This means the therapy we’re prescribing to our patients is still not good enough to prevent arterial thrombosis. An INR of 3 to 4 and/or the addition of low-dose aspirin may be the right thing to do in these cases,” he said
Direct Oral Anticoagulants in APS
Warfarin is the cornerstone of secondary thromboprophylaxis in APS, but INR monitoring is taxing on patients and providers alike. What about direct oral anticoagulants?
“We suspected that these may be a good solution, especially for refractory patients,” Dr. Cervera said. “Initial mechanistic studies showed promise, but the TRAPS study—the randomized controlled trial comparing rivaroxaban to warfarin in patients with APS—was discontinued early due to an excess of thrombosis in those receiving rivaroxaban.”9
The results of the TRAPS study led to warnings from international agencies to avoid the use of direct oral anticoagulants in patients with APS. But the patients studied were high-risk with triple positive aPLs. Dr. Cervera said, “There’s some new information and longer follow-up data that suggest it’s probably not necessary to avoid [direct oral anticoagulants] in all APS patients. Patients with venous thrombosis only, or only single or double aPL positivity may do okay on these drugs. We are revisiting this question.”
