Aspirin use among patients with thrombotic antiphospholipid antibody syndrome

Abstract Introduction Antiphospholipid syndrome (APS) is a leading acquired cause of thrombotic events and pregnancy morbidity in the United States. For patients with APS and a history of thrombosis, long-term anticoagulation is indicated to protect from devastating venous and/or arterial thrombotic events. However, even with anticoagulation, recurrent thromboses can occur, prompting consideration of adjunctive therapies, including antiplatelet drugs, to improve patient outcomes. At this time, there are no strong recommendations to guide whether aspirin should be added to anticoagulant therapy for patients with thrombotic APS, likely owing to limited data on this topic. We sought to assess patient characteristics, clinical features, and aspirin use in patients with thrombotic APS, as this information will be critical for designing a needed randomized clinical trial on this topic. Methods We conducted a retrospective cohort study of adults with thrombotic APS followed at a large academic medical center. Patients were enrolled if they met the 2006 Sydney Classification Criteria for Definite APS. Patients with isolated obstetric APS or only microvascular thrombosis were excluded. Patient data were abstracted from the electronic health record. Descriptive statistics were performed. Chi-square tests and t-tests were used to compare aspirin users to non-users as appropriate. Logistic regression was done to evaluate factors associated with aspirin use. Results A total of 182 patients with thrombotic APS were included in the analysis, with an average age of 46.6 years (standard deviation [SD] 17.0); 64 (35.2%) were male, and 167 (91.8%) self-identified as White. Thrombotic history was notable for venous thromboembolic disease for 91 patients (50.0%), arterial thrombosis for 53 (29.1.0%), and both for 38 (20.9%). Within this cohort, most were on anticoagulation with 133 (73.1%) on vitamin K antagonists (VKA), 26 (14.8%) on low molecular weight heparin, and 14 (7.7%) on a direct oral anticoagulant (DOAC). The remainder were using antiplatelet monotherapy—6 [3.3%] on non-aspirin antiplatelet drugs and 3 [1.6%] on aspirin. The cohort (n=182) had notable risk factors for cardiovascular disease, including 56.0% with a body mass index over 30 kg/m2, 36.3% on treatment for hypertension, 17.0% on treatment for hyperlipidemia, and 7.7% were tobacco users. Nearly one-half of patients had triple positive APS (45.6%), 22.0% had systemic lupus erythematosus, and 26.4% had one or more other autoimmune conditions. Within the cohort, 116 [63.7%] were on aspirin or had been on aspirin in the past, with 56 (30.8%) current aspirin users. Compared to non-aspirin users, aspirin users were older (mean age 50.7 versus 44.8 years, p=0.03) and more likely to have hyperlipidemia (32.1% versus 10.3%, p<0.001), but were similar to non-aspirin users with respect to sex, race, BMI, smoking history, hypertension, degree of sedentary lifestyle, number of autoimmune conditions, platelet count, antiphospholipid antibody test results, pregnancy morbidity history, and VKA use. DOAC users were less likely to be on aspirin (7.1% versus 32.7%, p=0.046). Compared to non-aspirin users, aspirin use was similar among patients with a history of both arterial and venous clotting (52.6%) to those with a history of isolated arterial thrombosis (43.4%, p=0.384), but significantly higher compared to those with a history of isolated venous thrombosis (14.3%, p<0.001). Regression analysis showed arterial thrombosis (odds ratio [OR] 6.8, 95% confidence interval [CI] 2.4-19.5, p<0.001), and hyperlipidemia (OR 3.2, 95% CI 1.2-8.7, p=0.02) to be most strongly associated with aspirin use. Of the 116 patients who ever used aspirin, aspirin was started for a variety of indications, with arterial thrombotic events being the most common. Aspirin was discontinued for 60 patients in the study cohort. Aspirin discontinuation generally occurred in response to a clinical status change like a new thrombotic episode, completion of pregnancy, bleeding, or due to reassessment of anticipated net clinical benefit. Conclusions Practice patterns for aspirin in APS are variable, with arterial thrombosis being the most common indication. Until better outcome data are available, aspirin use will require individualization; cardiovascular risk factor optimization also remains important for all patients.