By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology; Associate Dean for Clinical Affairs, NewYork Presbyterian/Weill Cornell Medical College
Dr. Fink reports no financial relationships relevant to this field of study.SOURCE: Seiffge DJ, Paciaroni M, Wilson D, et al; CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM Erlangen and Verona registry collaborators. Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Ann Neurol 2019;85:823-834.
Oral anticoagulation is effective in prevention of ischemic stroke and systemic embolism in patients with atrial fibrillation. For many years, vitamin K antagonists were the only oral agents available, but there are now several direct oral anticoagulants, including the thrombin inhibitor, dabigatran, and factor Xa inhibitors, apixaban and rivaroxaban. The direct oral anticoagulants have been shown to be at least as effective as warfarin, with a reduced risk of intracerebral hemorrhage. However, the clinical trials that investigated these medications allowed long delays following acute ischemic stroke, before the medications were started. The authors of this trial investigated the benefits and risks of early anticoagulation following acute ischemic stroke, and compared the effects of direct oral anticoagulants vs. vitamin K antagonists.
The investigators performed a meta-analysis by analyzing individual patient data from seven prospective cohort studies. Patients were included if they had atrial fibrillation and a recent cerebral infarct less than three months before starting oral anticoagulation, with a minimum follow-up of three months. They analyzed the association between the type of anticoagulation, direct oral anticoagulant vs. vitamin K antagonist, with the primary composite endpoint of recurrent ischemic stroke, intracerebral hemorrhage, or mortality, using a Cox proportional hazards regression model.
The investigators included 4,912 patients, with a median age of 78 years, 47.5% women, and median NIH stroke scale score of 5, with 45.9% of patients receiving vitamin K antagonist and 54.1% of patients receiving direct oral anticoagulants. The median time from the ischemic event to starting medication was five days for all medications. In follow-up, there were 262 acute ischemic strokes, for a rate of 4.4% per year; 71 intracranial hemorrhages, for a rate of 1.2% per year; and 439 deaths, or 7.4% per year during a follow-up of 5,970 patient-years. Compared to vitamin K antagonists, direct oral anticoagulation treatment was associated with a reduced risk for the composite endpoint (hazard ratio [HR], 0.82; P < 0.05) and a reduced intracerebral hemorrhage rate (HR, 0.42; P < 0.01). There was no difference between the two drug categories related to the risk of recurrent ischemic stroke or mortality. Overall, treatment with direct oral anticoagulants resulted in a reduced risk of poor clinical outcomes, primarily due to reduced risk of intracerebral hemorrhage.