Drug Interaction Exposure in Chronic Atrial Fibrillation Patients Maintained on Warfarin

Abstract

Atrial fibrillation (AF) affects approximately 2.3 million people in the United States and is an independent risk factor for the development of stroke. To prevent initial and recurring ischemic stroke, many high-risk patients with AF, are maintained on an oral anticoagulant such as warfarin sodium [1,2]. This medication has a narrow therapeutic-toxic index with high interindividual variability requiring frequent INR laboratory testing. For most patients with nonvalvular AF, a goal INR is in the range between 2.0-3.0. Insufficient doses (INR < 2.0) can lead to ischemic stroke and death [3], and excessive doses (INR ≥ 4) increase the risk of intracranial bleeding and other major bleedings with severe outcomes [4,5].Many AF patients have comorbid diseases requring routine drug therapy. Multiple medications with varying pharmacokinetic and pharmacodynamic mechanisms of action [6] can interact with warfarin to enhance or neutralize the beneficial effects on the risk of stroke or bleeding. The elderly are most likely to benefit from anticoagulant therapy but are also most likely to be taking the most medications and are at the highest risk for bleeding complications [7,8] often due to drug-drug interactions [9].A study was undertaken to determine the incidence of potential drug interactions in patients with chronic AF maintained on warfarin and to assess their impact on INR goals and average total health care costs. Patients were monitored by a decentralized managed care anticoagulation service. Data were retrospectively collected from clinical, pharmacy, research and administrative claims databases. Patient demographic data were stratified to include age, gender and risk factors. Clinical data collected included INR goal and actual values.Inclusion criteria for the study were adult patients (≥age 18) who were maintained on chronic warfarin sodium therapy with a diagnosis of atrial fibrillation (ICD9 427.31), continuously enrolled during CY 2000 and whose prescriptions were dispensed at the in-house managed care pharmacy. The text utilized to assess drug interactions was Hansten and Horn's "Managing Clinically Important Drug Interactions." The definitions used to categorize the exposures were as follows: Level 1: avoid combination; risk always outweighs benefit; Level 2: usually avoid combination; use only in special circumstances; Level 3: minimize risk; take action to reduce risk.A total of 86 patients on warfarin therapy for chronic atrial fibrillation met criteria for assessing drug interaction exposure. The demographics for these patients included: 71% male with 33.7% of the patients older than 75 years. Per ACCP criteria, 80.2% of the patients were identified as high risk for stroke. More than 75% of the patients (N = 65) were exposed to at least one potential drug interaction with warfarin during CY 2000.The frequency and type of interacting drugs is listed in Table 1. In the drug interaction exposure group, patients tended to be older, female and with a higher risk of stroke based on the ACCP criteria. A majori...