Rapid Change in Prescribing Behavior in Hospitals Participating in Get With The Guidelines–Stroke After Release of the Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) Clinical Trial Results
Background and Purpose—Physician prescribing patterns change slowly despite published randomized trials and consensus guidelines. We measure the effect of Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) trial on discharge prescribing patterns for patients with stroke and those with transient ischemic attack in the Get With The Guidelines (GWTG)–Stroke Program.
Methods—We analyzed discharge prescribing patterns of antithrombotic medications for patients admitted with ischemic stroke or transient ischemic attack at hospitals participating in GWTG-Stroke between October 2002 to January 2006. Clinical information by quarter was analyzed in relation to publication of the MATCH study. Frequency of discharge prescription of aspirin+clopidogrel post-MATCH publication was compared with the pre-MATCH period after adjusting for patient and hospital characteristics and clustering by hospital.
Results—A total of 107 872 patients at 632 sites were eligible to receive antithrombotic therapy at discharge. Use of aspirin+clopidogrel therapy declined from 22.4% to 15.4% of patients after the publication of MATCH (adjusted OR 0.62, 95% CI 0.56 to 0.70, P<0.0001). Analysis by quarter revealed a rapid and sustained decrease in use of aspirin+clopidogrel therapy for the remainder of the study period.
Conclusions—A rapid and sustained reduction in the frequency of aspirin+clopidogrel use in ischemic stroke and transient ischemic attack was observed after publication of the MATCH trial in the absence of MATCH-specific GWTG-Stroke initiatives and preceding an American Heart Association guideline update.
Translation of findings from randomized controlled trials to clinical practice is often delayed. There is a difference in “adoption” of new information and “relinquishment” of current information. Physicians respond faster to clinical studies with negative results and are therefore “relinquished” of current information.1
We hypothesized that the combined use of aspirin+clopidogrel in ischemic stroke would decline after publication of the Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) trial in July 2004,2 which showed no benefit of this therapy for the primary composite outcome (ischemic stroke, myocardial infarction, vascular death, and rehospitalization for an acute ischemic event). This hypothesis was tested using data from the Get With the Guidelines–Stroke (GWTG-Stroke) Program.3
GWTG-Stroke is a national quality improvement initiative and stroke registry. Design and conduct of the program have been previously described.3 Patients admitted with stroke or transient ischemic attack in hospitals participating in GWTG-Stroke were potentially eligible (n=188 848). A specified study period from October 2002 to January 2006 was chosen to have an even number of months before and after publication of MATCH. Patients without ischemic strokes (n=29 510), not in the study period (n=26 656), transferred to other acute care facilities or expired (n=18 373), or with contraindications to antithrombotics (n=6437) were excluded. Therefore, the analysis sample included 107 872 patients from 632 hospitals. Missing data on patient characteristics in <1% of subjects were imputed. Clinical information aggregated by quarter was analyzed in relation to publication of MATCH. Patients discharged before publication (pre-MATCH n=25 332) were compared with those discharged after publication (post-MATCH n=82 540). Multivariable regression analysis was performed to examine the independent effect of MATCH publication on adjusted odds of discharge prescription of aspirin+clopidogrel. The generalized estimating equation approach was used in regression analyses to adjust for clustering within hospitals. We did 2 sensitivity analyses including: (1) only hospitals that supplied data during the entire pre-MATCH and post-MATCH periods; and (2) excluding patients with coronary artery disease or peripheral vascular disease. Statistical analyses were performed using SAS Version 9.1.
The study included 107 872 patients from 632 hospitals. Demographics and vascular risk factors were relatively evenly distributed between the pre- and post-Match groups (Table). Because of the large sample size, many of these small differences were statistically significant.
Antithrombotic prescribing patterns at discharge were different between the pre-MATCH and post-MATCH groups (Figure 1). Use of aspirin+clopidogrel therapy declined from 22.4% to 15.4% of patients after MATCH publication (adjusted OR 0.62, 95% CI 0.56 to 0.70, P<0.0001). Analysis by quarter revealed a rapid and sustained decrease in the frequency of patients discharged on combination aspirin+clopidogrel post-MATCH (Figure 2). In a sensitivity analysis including 196 hospitals (48 328 patients) that submitted data during the entire study period, use of aspirin+clopidogrel declined after MATCH publication (22.3% to 15.3%, adjusted OR 0.62, 95% CI 0.55 to 0.70, P<0.0001). In a sensitivity analysis restricted to patients without coronary artery disease or peripheral vascular disease (n=77 350), use of aspirin+ clopidogrel declined from 21.3% to 13.4% (adjusted OR 0.60, 95% CI 0.53 to 0.67).
MATCH publication led to a rapid and sustained decrease in prescription of aspirin+clopidogrel at discharge among hospitals participating in GWTG-Stroke, although a guideline statement advising avoidance of aspirin+clopidogrel therapy did not appear until after the study period.4 Nonetheless, aspirin+clopidogrel therapy remained the second most commonly prescribed antithrombotic regimen after MATCH (Figure 1). Furthermore, rates of aspirin+clopidogrel use remained stable for 1.25 years after MATCH publication with no evidence of continuing decline (Figure 2). These findings were unchanged in sensitivity analyses excluding patients with coronary artery disease or peripheral vascular disease and hospitals that joined or left the program during the study period (done to exclude confounding that results from differences over time in the participating hospital population).
In the pre-MATCH period, aspirin+clopidogrel was presumably prescribed because beneficial effects seen in trials for coronary artery disease5,6 were extrapolated to the stroke and transient ischemic attack population. The MATCH trial showed that, compared with clopidogrel alone, aspirin+clopidogrel had no significant effect on recurrent ischemic events and increased the risk of life-threatening hemorrhage.2 In light of this new knowledge, there was a rapid change in physician prescribing behavior with a substantial decrease in aspirin+clopidogrel therapy in the quarter during which the MATCH results appeared.
Reasons for persistent prescription of aspirin+clopidogrel in approximately 15% of patients discharged after MATCH are less clear. The proportion was the same when excluding patients with coronary artery disease, who may have had an independent indication for aspirin+clopidogrel because of either recent acute coronary syndrome or coronary stenting. Some patients with stroke and patients with transient ischemic attack were appropriately prescribed aspirin+clopidogrel because of recent stenting of an intracranial artery or extracranial internal carotid artery. It seems unlikely, however, that recent stent cases could account for the entire population treated with aspirin+clopidogrel given that stenting for cerebrovascular disease remains relatively uncommon.7
This study has several limitations. We have no information on reasons why physicians prescribed aspirin+clopidogrel despite lack of evidence and even increased risk of harm. Hospitals in GWTG-Stroke are voluntarily participating in a stroke quality improvement initiative and the rate of response to new trial information may be different compared with nonparticipating hospitals, although no MATCH-specific quality initiatives were launched in GWTG-Stroke concurrent with the trial publication.
Our finding of rapid relinquishment of information in the setting of safety concerns is consistent with other studies,8 including a study from a smaller US registry that reported a fall in aspirin+clopidogrel use in the 3 months after MATCH publication.9 These findings suggest that diffusion of knowledge is more effective when relative risks and potential harm, rather than potential benefits, are highlighted. Further research will be needed to determine other factors that influence physician prescriptions.
Sources of Funding
Get With the Guidelines–Stroke is funded by the American Heart Association and the American Stroke Association. The program is also supported in part by unrestricted educational grants to the American Heart Association by Pfizer, Inc, New York, NY, and the Merck-Schering Plough Partnership (North Wales, Pa), who did not participate in the design, analysis, manuscript preparation, or approval.
L.L. is a member of the Duke Clinical Research Institute, which serves as the American Heart Association (AHA) GWTG data coordinating center. K.A.L. receives research support from the National Institutes of Health (significant) and the Agency for Healthcare Research and Quality (significant). A.F.H. is a member of the Duke Clinical Research Institute, which serves as the AHA GWTG data coordinating center; receives research support from Johnson & Johnson and Merck & Co; serves on the speakers’ bureau for Novartis; and receives honoraria from AstraZeneca and Medtronic. G.C.F. receives research support from the National Institutes of Health (significant); served as a consultant to Merck, Bristol Myers Squibb, and Sanofi-Aventis (all modest); received speaker honoraria from Pfizer, Merck, Bristol Myers Squibb, and Sanofi-Aventis (all significant); and is an employee of the University of California, which holds a patent on retriever devices for stroke (significant). L.H.S. serves as a consultant to the Massachusetts Department of Public Health. E.E.S. receives research support from the National Institutes of Health (NINDS R01 NS062028), the Canadian Stroke Network, and the Hotchkiss Brain Institute and Canadian Institutes for Health Research and salary support from the Canadian Institutes for Health Research.
- Received March 11, 2010.
- Revision received April 12, 2010.
- Accepted April 14, 2010.
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