In patients with a history of venous thrombosis and APS, vitamin K antagonist therapy with an international normalized ratio (INR) goal of 2–3 is recommended. If the clot was unprovoked, then long-term therapy is indicated. In a patient with arterial thrombosis and APS, vitamin K antagonist therapy with an INR goal of 2–3 or 3–4 is recommended depending on thrombosis and bleeding risk of the patient. Alternatively, vitamin K antagonist therapy with an INR goal of 2–3 plus low-dose aspirin can be considered for these patients.1
Dr. Tektonidou noted the advent of direct oral anticoagulants has resulted in a desire to see if these agents can be used in patients with APS instead of vitamin K antagonist therapy. Therapy with vitamin K antagonist is challenging, requiring frequent blood tests and significant food restrictions. The therapy also has the potential for significant drug interactions. Despite the intellectual appeal of using direct oral anticoagulants for the treatment of thrombotic APS, evidence indicates it is inappropriate for most patients.
The Trial on Rivaroxaban in Antiphospholipid Syndrome (TRAPS) study was conducted in patients with high-risk APS, defined on the basis of the patients’ clinical history and triple positivity of lupus anticoagulant, anti-cardiolipin antibodies and anti-beta-2 glycoprotein antibodies. The study’s 120 patients were randomized to receive rivaroxaban or warfarin. Researchers followed these patients over time and evaluated prevention of thrombosis, major bleeding or vascular mortality as the study’s primary end point. Before the study concluded, the trial was stopped prematurely by the adjudication and safety committee due to an excess of events in the rivaroxaban group.3
In 2019, the European Medicines Agency advised direct oral anticoagulants not be used for patients with a history of thrombosis and APS, particularly for those with triple-positive disease.4
Dr. Tektonidou indicated that additional studies, such as ASTRO-APS, have shown that direct oral anticoagulants should be avoided even in patients at low risk of APS, such as those with one or two positive antiphospholipid antibodies and a lower risk clinical history.5
Clinical Pearls
When a patient experiences recurrent thrombotic events despite appropriate anticoagulation, said Dr. Tektonidou, consider the possibility of medication non-compliance before making medication adjustments. If necessary, such adjustments may include increasing the INR goal, adding low-dose aspirin or switching from a vitamin K antagonist to low molecular weight heparin.
Clinicians should be aware that patients with APS have an increased prevalence of traditional cardiovascular risk factors, metabolic syndrome and subclinical atherosclerosis than the general population. Research by Dr. Tektonidou et al. has shown that we are doing worse at achieving traditional cardiovascular risk factor targets in patients with APS—especially those with high/very high risk disease—than in patients with rheumatoid arthritis and diabetes mellitus.6 Hypertension, obesity and hyperlipidemia are all co-morbidities that clinicians must pay attention to in patients with APS, especially in individuals with concomitant systemic lupus erythematosus for whom atherosclerosis progression is already greater than that of the general population.
