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Should Newer Oral Anticoagulants Be Used as First-Line Agents to Prevent Thromboembolism in Patients With Atrial Fibrillation and Risk Factors for Stroke or Thromboembolism?
Newer Oral Anticoagulants Should Be Used as First-Line Agents to Prevent Thromboembolism in Patients With Atrial Fibrillation and Risk Factors for Stroke or Thromboembolism
ChristopherB. Granger, MD; Luciana V. Armaganijan, MD
he incidence of atrial fibrillation (AF) appears to be increasing, even after adjustment for aging of the population.1 One in 4 people is projected to develop AF in his or her lifetime.2 Patients with AF have a 5-fold increased risk of stroke, and it is estimated that 15% to 20% of all strokes are attributable to AF. Moreover, death and disability fromstroke complicating AF are particularly high.3 Thus, stroke related to AF is a substantial and growing public health burden.
Response by Ansell on p 164
Warfarin results in a two-thirds reduction in stroke on the basis of a meta-analysis of the randomized controlled trials4 (Figure). However, warfarin is grossly underused. In a relatively healthy insured population, 55% of eligiblepatients with AF received warfarin, and the rates dropped off substantially in the elderly, who have the greatest need.5 This low proportion of use and even greater underuse in higher-risk patients have been consistent findings across a number of US and European registries.6 – 8 In addition, not only is warfarin underused, but when it is used, it is used suboptimally.5 An inception cohort of elderlypatients started on warfarin found that 28% of patients had discontinued warfarin by 1 year.9 Rates of major bleeding were very high, at 20% for patients
with CHADS2 (an acronym for congestive heart failure, hypertension, age 75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score 4, during the first year, illustrating the vulnerability of patients on warfarin duringinitiation. International normalized ratios (INRs) were in the target range of 2.0 to 3.0 only 58% of the time. Reasons for underuse of warfarin and inability to consistently achieve target INR, at least in part, relate to pharmacological properties of the drug, including unpredictable anticoagulant effects, genetic variability in metabolism, multiple drug and food interactions, a narrow therapeuticwindow, and the resulting need for inconvenient monitoring. A large body of evidence shows a strong relationship of time in therapeutic range and risk of stroke, with an overview of 37 studies showing a 1% absolute annual increased risk of stroke for every 10% decrease in time in therapeutic range.10 Registries, often performed in settings with better than typical quality of warfarin use, have...