Options to Prevent Strokes in Patients with Atrial Fibrillation
Orlando—Patients with atrial fibrillation (AF) typically take warfarin to prevent strokes, but pharmaceutical companies are investing significant time and money to find alternative therapies. The FDA approved Pradaxa® (dabigatran etexilate) in October 2010 and Xarelto® (rivaroxaban) in November 2011. In phase 3 trials, both oral drugs were noninferior to warfarin in reducing strokes and systemic embolism, and they were also safer than warfarin.
Michael Miller, MD, professor of medicine at the University of Maryland in Baltimore, discussed the treatment options at the Spring Managed Care Forum in a session titled The Unmet Needs in the Management of Stroke Prevention in Atrial Fibrillation.
Dr. Miller said AF is the most common sustained cardiac arrhythmia, affecting >2.3 million people in the United States. It is typically found in men and the elderly. By 2050, the prevalence of AF is expected to increase by ≥2.5 times, according to Dr. Miller.
There are numerous causes of AF. Noncardiovascular reasons include acute or chronic alcohol ingestion, obesity, pulmonary embolism, severe lung diseases, and thyroid disorders, while cardiovascular causes include coronary artery disease, heart failure, primary electrical disorders, and valvular heart disease.
Dr. Miller said stroke is the most common complication of AF, citing studies that have shown patients with AF have a 5-fold increase in stroke risk and approximately 15% of all strokes are caused by AF. A common measurement tool for stroke risks in patients with AF is the CHADS2 score (congestive heart failure, hypertension, age >75 years, diabetes, and prior stroke/transient ischemic attack).
In patients with AF, treatment goals include preventing stroke, improving symptoms and quality of life, reducing costs, and prolonging survival. Warfarin is the most common pharmacologic therapy for preventing strokes.
Dr. Miller discussed several trials that collectively found warfarin reduced the incidence of stroke by approximately 64% compared with placebo. He also mentioned the BAFTA (Birmingham Atrial Fibrillation Treatment of the Aged) trial of 973 patients ≥75 years of age who had AF. The authors found the risk per year of fatal or disabling stroke, intracerebral hemorrhage, or systemic embolism was 1.8% for patients taking warfarin compared with 3.8% for patients taking aspirin (P=.003). There was no significant difference in the risk per year of major extracranial hemorrhage (1.4% for warfarin and 1.6% for aspirin).
However, Dr. Miller said warfarin has a narrow therapeutic window and is associated with a high rate of adverse events that often causes patients to stop taking the medication as prescribed. He then discussed pivotal trials of dabigatran etexilate and rivaroxaban in patients with AF.
In the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, patients who took 110 mg or 150 mg of dabigatran etexilate twice daily had noninferior rates of stroke and systolic embolism compared with patients who took warfarin. In addition, both dabigatran etexilate groups had significantly lower rates of intracranial hemorrhage compared with the warfarin group.
In the ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) study, patients who took 15 mg or 20 mg of rivaroxaban once daily had a noninferior event rate of stroke or systemic embolism compared with the warfarin group. Patients taking rivaroxaban had a significant reduction in the risk of hemorrhagic stroke and less fatal bleeding than the warfarin group, but they had more major bleeding events.
Dr. Miller warned that there are some challenges associated with the new anticoagulants. They have no established therapeutic range, it is difficult to assess compliance to the medications, and there is a lack of head-to-head studies comparing the novel drugs.
