Title:
Antithrombotic Utilization Trends after Noncardioembolic Ischemic Stroke or TIA in the Setting of Large Antithrombotic Trials (2002-2009).

Abstract:
Several large trials published over the last decade have significantly altered recommended guidelines for therapy following a noncardioembolic ischemic stroke or transient ischemic attack (TIA). The impact of these studies on patient usage of alternative antithrombotic agents has hitherto not been evaluated. We examined the usage of these agents in the United States over the last decade, with regard to the publication of the Management of Atherothrombosis with Clopidogrel in High-Risk Patients (MATCH), European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), and Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) clinical trials, in order to test the hypothesis that resulting recommendations are reflected in usage trends.
Antithrombotic utilization was prospectively collected as part of the National Ambulatory Medical Care Survey (NAMCS) on a total of 53,608,351 patients in the United States between 2002 and 2009. Patients with a history of ischemic stroke or TIA were included. Patients were excluded if there was a prior history of subarachnoid or intracerebral hemorrhage, or if other indications for antithrombotic treatment were present, including deep venous thrombosis, pulmonary embolism, atrial fibrillation or flutter, mechanical cardiac valve replacement, congestive heart failure, coronary artery disease, peripheral arterial disease, and rheumatoid arthritis. Annual utilization of the following antithrombotic strategies was compared in 53,608,351 patients: 1) aspirin monotherapy, 2) clopidogrel monotherapy, 3) combined clopidogrel and aspirin, 4) combined extended-release dipyridamole (ERDP) and aspirin, and 5) warfarin. Annual utilization was compared before and after publication of MATCH, ESPRIT, and PRoFESS in 2004, 2006, and 2008, respectively. Trend analysis was performed with the Mantel-Haenszel test for trends. Sensitivity analysis of demographic and clinical characteristics stratified by antithrombotic-usage group was performed using the Wald Chi-square test.
Utilization of combined clopidogrel and aspirin increased from 3.3% to 6.7% after the MATCH trial (p<0.0001). Following the results of the ESPRIT trial, utilization of combination ERDP and aspirin decreased from 4% to 3% (p<0.0001), utilization of clopidogrel declined from 6.8% to 6% (p<0.0001), and utilization of aspirin remained essentially unchanged. After the PRoFESS trial, utilization of clopidogrel increased from 5% to 9% (p<0.0001), utilization of ERDP-aspirin increased from 3 % to 4.6% (p<0.0001), and utilization of aspirin increased from 15.6% to 17.8% (p<0.0001). The proportion of patients on none of the five antithrombotic secondary prevention strategies steadily declined from a peak of 74% in 2003 to 57% by 2009.
The impact of the MATCH, ESPRIT, and PRoFESS trials on antithrombotic utilization has been variable. These findings highlight the importance of addressing factors that affect the implementation of findings from major clinical trials.