Effect of Extended Thromboprophylaxis with Non-Vitamin K Antagonist Oral Anticoagulant on the Risk of Stroke and Major Bleeding in Acutely Ill Hospitalized Medical Patients: A Meta-Analysis of Randomized Controlled Trials (S54.001)

Objective: The study aims to assess the effect of extended thromboprophylaxis with non-vitamin K antagonist oral anticoagulant (NOAC) on the risk of stroke and major bleeding among patients hospitalized with an acute medical illness based on data from randomized controlled trials. Background: Among acutely ill hospitalized medical patients, treatment with NOAC for 30–42 days is effective in preventing symptomatic deep vein thrombosis or pulmonary embolism compared with standard-of-care enoxaparin for 6–14 days. The risk-benefit profile of NOAC on stroke prophylaxis has not been studied in this setting. Design/Methods: We performed a systematic literature search in MEDLINE, Embase, and ClinicalTrials.gov for randomized controlled trials comparing the effect of extended-duration NOAC with standard-duration enoxaparin on the stroke and bleeding endpoint. Three Phase III studies were identified: ADOPT (NCT00457002), MAGELLAN (NCT00571649), and APEX (NCT01583218). The relative risk of stroke and major bleeding at 30 to 90 days was compared between NOAC and enoxaparin using the Mantel-Haenszel test in a random effects model. Results: A total of 21,831 hospitalized medical patients randomized to either extended NOAC (apixaban, rivaroxaban, or betrixaban) or enoxaparin were included. Compared with enoxaparin, NOAC reduced the risk of stroke at 30 to 90 days by 35% (RR=0.65 [95% CI: 0.47–0.91]; P=0.01) but doubled the risk of major bleeding (RR=1.99 [95% CI: 1.08–3.65]; P=0.03). Betrixaban at 80 mg daily demonstrated a significant benefit in stroke prevention (RR=0.47 [95% CI: 0.25–0.88]; P=0.02) without causing more major bleedings (RR=0.94 [95% CI: 0.47–1.90]; P=0.86). There was no significant heterogeneity across studies in stroke (I2=0%; P=0.76) or bleeding (I2=58%; P=0.09). Conclusions: Extended thromboprophylaxis with NOAC reduces stroke but is associated with a greater risk of major bleeding up to 90 days compared to standard-of-care enoxaparin. Future prospective trials are required to identify the high-risk subsets in which the benefit of NOAC significantly outweighs the associated hemorrhagic risk among hospitalized medical patients. Disclosure: Dr. Marszalek has nothing to disclose. Dr. Jamil has nothing to disclose. Dr. Jamil has nothing to disclose. Dr. Kumar has nothing to disclose. Dr. Kahe has nothing to disclose. Dr. Karimi has nothing to disclose. Dr. Chi has received research support from Portola, Bayer, and Janssen Research.