Antithrombotic Utilization Trends after Noncardioembolic Ischemic Stroke or Tia in the Setting of Large Antithrombotic Trials (2002–2009)

Abstract

Background and Purpose—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.
Methods—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.
Results—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.
Conclusions—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.