In 2008, approximately 7 million individuals were reported to have a history of stroke [
Between 2001 and 2006, several clinical trials were published that may influence clinicians’ prescribing of anti-platelet therapy to IS patients: CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) [
Despite these major changes in the evidence and recommendations for antiplatelet therapy in vascular patients, few studies have examined temporal trends in physicians’ prescribing of antiplatelet therapy to IS stroke patients in the ambulatory setting or in a population-based fashion [
This study was a retrospective analysis of two national surveys: (1) National Ambulatory Medical Care Survey (NAMCS) [
We identified all patients age 18 years or older who had an ambulatory visit with a primary physician diagnosis of ischemic stroke (IS) using valid ICD-9-CM codes (433.x1, 434.xx, 436.xx) [
The primary outcome was an ambulatory IS visit with medication mention for antiplatelet agents. The antiplatelet agents considered for this study were aspirin, clopidogrel, dipyridamole, and ticlopidine as these agents were available during 2000 to 2007. We then categorized the antiplatelet agents into the following mutually exclusive categories: (1) aspirin only, (2) clopidogrel only, (3) aspirin and clopidogrel, (4) aspirin and dipyridamole, (5) dipyridamole only, and (6) ticlopidine.
The NAMCS [
The various patient characteristics considered in the analysis included race (white, black, and other), age (18–44 years, 45–64 years, and ≥65 years), gender (male and female), and primary payment source for the visit (private, Medicare, Medicaid and other). The various physician office/hospital characteristics in the analysis included region of the physician office or the hospital as defined by the US census bureau (Northeast, Midwest, South, West), location (urban: Metropolitan Statistical Area (MSA), rural: non-MSA), and visit setting (physician office, hospital OPD, and hospital ED).
Patient visit weights were used to assess the national estimate on annual IS visits with and without a mention of antiplatelet agents. Temporal changes in the proportion of IS visits resulting in mention of antiplatelet agents were assessed during the 8-year study period, that is, 2000 to 2007, using the Cochran-Mantel-Haenszel test for trend. We further stratified the utilization trends by visit setting, that is, physician office, hospital ED, and hospital OPD, using indicator variable for visit setting available in the dataset. Associations between antiplatelet prescribing and patient and physician office/hospital characteristics were tested using the Chi-square test. All the statistical analyses were performed in SAS-callable SUDAAN (version 10.0.1 hosted on the Windows platform) to account for the complex survey design of the NAMCS and NHAMCS and to provide weighted results that reflect population estimates. This study was approved by the Institutional Review Board at the Ohio State University.
During the 8 year period, there were 9.5 million ischemic stroke-related ambulatory visits of which 6.8 million (71.1%) occurred in a physician office, 0.3 million (3.4%) in a hospital OPD, and 2.4 million (25.5%) in a hospital ED (Table
Ischemic stroke patient characteristics and antiplatelet agents prescribed: NAMCS, NAMCS 2000–2007a,b.
|
Survey Year | |||||||
---|---|---|---|---|---|---|---|---|
2000-01 | 2002-03 | 2004-05 | 2006-07 | |||||
( |
( |
( |
( |
|||||
Population estimate | % | Population estimate | % | Population estimate | % | Population estimate | % | |
Total ischemic stroke visits |
|
|
|
|
|
|
|
|
| ||||||||
Race | ||||||||
White | 1,605,408 | 72.3% | 1,760,410 | 78.6% | 2,266,603 | 77.7% | 1,716,210 | 79.8% |
Black | 448,739 | 20.2% | 184,064 | 8.2% | 551,036 | 18.9% | 392,536 | 18.3% |
Other | 167,130 | 7.5% | 294,066 | 13.1% | 100,011 | 3.4% | 42,105 | 2.0% |
| ||||||||
Region | ||||||||
Northeast | 340,302 | 15.3% | 509,922 | 22.8% | 393,472 | 13.5% | 339,938 | 15.8% |
Midwest | 491,280 | 22.1% | 366,347 | 16.4% | 1,058,706 | 36.3% | 536,408 | 24.9% |
South | 703,364 | 31.7% | 579,150 | 25.9% | 1,119,719 | 38.4% | 928,226 | 43.2% |
West | 686,331 | 30.9% | 783,121 | 35.0% | 345,753 | 11.9% | 346,279 | 16.1% |
| ||||||||
Age | ||||||||
18–44 years | 46,907 | 2.1% | 141,937 | 6.3% | 137,665 | 4.7% | 116,652 | 5.4% |
45–64 years | 549,189 | 24.7% | 536,338 | 24.0% | 885,617 | 30.4% | 673,635 | 31.3% |
≥65 years | 1,625,181 | 73.2% | 1,560,265 | 69.7% | 1,894,368 | 64.9% | 1,360,564 | 63.3% |
| ||||||||
Gender | ||||||||
Female | 1,177,727 | 53.0% | 1,196,813 | 53.5% | 1,572,905 | 53.9% | 834,076 | 38.8% |
Male | 1,043,550 | 47.0% | 1,041,727 | 46.5% | 1,344,745 | 46.1% | 1,316,775 | 61.2% |
| ||||||||
Insurancec | ||||||||
Private insurance | 523,035 | 23.5% | 553,314 | 24.7% | 860,712 | 29.5% | 633,122 | 29.4% |
Medicare | 1,488,002 | 67.0% | 1,364,738 | 61.0% | 1,538,343 | 52.7% | 1,224,087 | 56.9% |
Medicaid | 76,721 | 3.5% | 61,621 | 2.8% | 106,824 | 3.7% | 128,987 | 6.0% |
Other | 90,939 | 4.1% | 206,476 | 9.2% | 145,752 | 5.0% | 75,490 | 3.5% |
| ||||||||
Location | ||||||||
MSAd | 1,580,138 | 71.1% | 2,003,578 | 89.5% | 2,546,768 | 87.3% | 1,986,970 | 92.4% |
Non-MSA | 641,139 | 28.9% | 234,962 | 10.5% | 370,882 | 12.7% | 163,881 | 7.6% |
| ||||||||
Antiplatelet prescribing | ||||||||
Overall antiplatelet agents | 623,998 | 28.1% | 641,900 | 28.7% | 1,101,786 | 37.8% | 1,010,462 | 47.0% |
Aspirin only | 360,067 | 16.2% | 244,855 | 10.9% | 213,034 | 7.3% | 377,002 | 17.5% |
Clopidogrel only | 107,873 | 4.9% | 151,764 | 6.8% | 327,148 | 11.2% | 231,652 | 10.8% |
Aspirin and clopidogrel | 23,542 | 1.1% | 192,779 | 8.6% | 456,787 | 15.7% | 305,702 | 14.2% |
Aspirin and dipyridamole | 118,183 | 5.3% | 47,861 | 2.1% | 104,817 | 3.6% | 96,106 | 4.5% |
Dipyridamole only | 3,148 | 0.1% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% |
Ticlopidine only | 11,185 | 0.5% | 4,641 | 0.2% | 0 | 0.0% | 0 | 0.0% |
| ||||||||
Setting | ||||||||
Physician office | 1,502,370 | 67.6% | 1,550,687 | 69.3% | 2,231,054 | 76.5% | 1,493,699 | 69.4% |
Hospital OPD | 65,065 | 2.9% | 102,196 | 4.6% | 62,847 | 2.2% | 92,825 | 4.3% |
Hospital ED | 653,842 | 29.4% | 585,657 | 26.2% | 623,749 | 21.4% | 564,327 | 26.2% |
aNAMCS: National Ambulatory Medical Care Survey, NHAMCS: National Hospital Ambulatory Medical Care Survey.
bPopulation estimates were calculated using SAS-callable SUDAAN software, version 10.0.1 (Research Triangle Institute) to obtain proper variance estimations that accounted for the complex sampling design of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey and results that were weighted to reflect national population estimates.
cInsurance (payment source) does not sum to 100% because of missing data, dMSA: Metropolitan Statistical Area.
Table
Association between patient demographic and physician office/hospital characteristics and antiplatelet agent prescribed: NAMCS, NHAMCS 2000–2007a , b.
Antiplatelet medication | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Characteristic | Aspirin only | Clopidogrel only | Aspirin and clopidogrel | Aspirin and dipyridamole | ||||||||
( |
( |
( |
( |
|||||||||
Population estimate | % |
|
Population estimate | % |
|
Population estimate | % |
|
Population estimate | % |
|
|
| ||||||||||||
Total | 1,194,958 | — | 818,437 | — | 978,810 | — | 366,967 | — | ||||
| ||||||||||||
Race | ||||||||||||
White | 958,151 | 80.2% | 0.40 |
581,489 | 71.0% | 0.68 |
708,008 | 72.3% | 0.91 |
341,339 | 93.0% | 0.11 |
Black | 201,745 | 16.9% | 150,228 | 18.4% | 203,509 | 20.8% | 22,867 | 6.2% | ||||
Other | 35,062 | 2.9% | 86,720 | 10.6% | 67,293 | 6.9% | 2761 | 0.8% | ||||
| ||||||||||||
Region | ||||||||||||
Northeast | 304,874 | 25.5% | 0.38 |
82,604 | 10.1% | 0.52 |
111,832 | 11.4% | 0.47 |
62,510 | 17.0% | 0.75 |
Midwest | 217,812 | 18.2% | 287,327 | 35.1% | 161,843 | 16.5% | 108,731 | 29.6% | ||||
South | 433,594 | 36.3% | 259,449 | 31.7% | 466,195 | 47.6% | 84,482 | 23.0% | ||||
West | 238,678 | 20.0% | 189,057 | 23.1% | 238,940 | 24.4% | 111,244 | 30.3% | ||||
| ||||||||||||
Age | ||||||||||||
18–44 years | 65,453 | 5.5% | 0.39 |
10,958 | 1.3% |
|
17,561 | 1.8% | 0.20 |
12364 | 3.4% | 0.90 |
45–64 years | 436,552 | 36.5% | 116,735 | 14.3% | 404,818 | 41.4% | 95,313 | 26.0% | ||||
≥65 years | 692,953 | 58.0% | 690,744 | 84.4% | 556,431 | 56.8% | 259,290 | 70.7% | ||||
| ||||||||||||
Gender | ||||||||||||
Female | 632,517 | 52.9% | 0.71 |
522,671 | 63.9% | 0.15 |
192,540 | 19.7% |
|
113,778 | 31.0% | 0.22 |
Male | 562,441 | 47.1% | 295,766 | 36.1% | 786,270 | 80.3% | 253,189 | 69.0% | ||||
| ||||||||||||
Insurancec | ||||||||||||
Private insurance | 355,686 | 29.8% | 0.31 |
187,508 | 22.9% | 0.47 |
405,119 | 41.4% | 0.21 |
64,802 | 17.7% | 0.73 |
Medicare | 656,260 | 54.9% | 572,429 | 69.9% | 461,148 | 47.1% | 267,898 | 73.0% | ||||
Medicaid | 71,523 | 6.0% | 26,884 | 3.3% | 53,025 | 5.4% | 10,678 | 2.9% | ||||
Other | 55,345 | 4.6% | 21,151 | 2.6% | 14,927 | 1.5% | 10,620 | 2.9% | ||||
| ||||||||||||
Location | ||||||||||||
MSAd | 994,903 | 83.3% | 0.82 |
646,403 | 79.0% | 0.58 |
852,053 | 87.0% | 0.72 |
224,322 | 61.1% | 0.30 |
Non-MSA | 200,055 | 16.7% | 172,034 | 21.0% | 126,757 | 13.0% | 142,645 | 38.9% | ||||
| ||||||||||||
Setting | ||||||||||||
Physician office | 711,071 | 59.5% |
|
726,058 | 88.7% |
|
870,856 | 89.0% |
|
317,518 | 86.5% | 0.21 |
Hospital OPDe | 56,218 | 4.7% | 49,195 | 6.0% | 5,305 | 0.5% | 8,951 | 2.4% | ||||
Hospital ED | 427,669 | 35.8% | 43,184 | 5.3% | 102,649 | 10.5% | 40,498 | 11.0% | ||||
| ||||||||||||
Year | ||||||||||||
2000-01 | 360,067 | 30.1% | 0.13 |
107,873 | 13.2% | 0.22 |
23,542 | 2.4% |
|
118,183 | 32.2% | 0.62 |
2002-03 | 244,855 | 20.5% | 151,764 | 18.5% | 192,779 | 19.7% | 47,861 | 13.0% | ||||
2004-05 | 213,034 | 17.8% | 327,148 | 40.0% | 456,787 | 46.7% | 104,817 | 28.6% | ||||
2006-07 | 377,002 | 31.5% | 231,652 | 28.3% | 305,702 | 31.2% | 96,106 | 26.2% |
aNAMCS: National Ambulatory Medical Care Survey, NHAMCS: National Hospital Ambulatory Medical Care Survey.
bPopulation estimates were calculated using SAS-callable SUDAAN software, version 9.0.1 (Research Triangle Institute) to obtain proper variance estimations that accounted for the complex sampling design of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey and results that were weighted to reflect national population estimates.
cInsurance (payment source) does not sum to 100% because of missing data, dMSA: Metropolitan Statistical Area.
eOPD: Outpatient Department.
Among the IS patients, the proportion of patients receiving antiplatelet drugs increased from 28.1% in 2000-01 to 47.1% in 2006-07 (
Antiplatelet prescribing trends among patients with ischemic stroke: NAMCS, NHAMCS, 2000–2007. NAMCS: National Ambulatory Medical Care Survey; NHAMCS: National Hospital Ambulatory Medical Care Survey;
No significant changes in prescribing of dipyridamole-aspirin combination were seen (
Prescribing trends varied significantly by the physician practice setting (Figure
Antiplatelet prescribing trends among patients with ischemic stroke, by visit setting: 2000–2007. Physician office visits based on National Ambulatory Medical Care Survey data; Hospital ED/OPD visits based on National Hospital Ambulatory Medical Care Survey data; OPD: Outpatient Department; ED: Emergency Department;
To the authors knowledge this is the first comprehensive study evaluating the ambulatory (physician office, hospital ED, and hospital OPD) prescribing trends for antiplatelet agents among community dwelling IS patients. We have identified significant changes in utilization pattern of antiplatelet agents among IS patients. During the 8 year study period (2000–2007), clopidogrel-aspirin prescribing increased significantly in the physician office setting. In contrast, the prescribing of clopidogrel-aspirin combination remained relatively low and stable in the hospital OPD and ED during the same period. However, the prescription of aspirin monotherapy increased dramatically in the hospital OPD and ED settings while it declined significantly in the physician office setting. We found that prescribing of clopidogrel alone was considerably higher among elderly compared with younger IS patients. Prior study findings suggest that the risk of bleeding is higher among elderly patients using aspirin plus clopidogrel combination compared with patients only using clopidogrel [
Our findings suggest that physician prescribing of clopidogrel-aspirin combination may have been influenced by the publication of three major clinical trials. Findings from both CURE (08/01) [
During the period under consideration for this study, MATCH [
We found a significant increase in prescribing of aspirin monotherapy in the hospital OPD and ED settings from 2000 to 2007. One of the reasons for this increased use may be the publication of the Chinese Acute Stroke Trial [
Surprisingly, during the entire study period the prescribing of dipyridamole-aspirin combination remained low even though this combination was shown to be effective in reducing the risk of recurrent IS or death as compared to aspirin monotherapy in the European Stroke Prevention Study 2 (ESPS-2) published in 1996 [
In the wake of the above findings, there is a need to recognize certain limitations of this study. In this study the proportion of patients receiving antiplatelet medications ranged from 28% to 47% compared to 89% reported by Hill and Johnston [
Our study highlights important changes in the prescribing patterns of antiplatelet therapy among IS patients. Our findings suggest that even with the lack of adequate efficacy evidence, safety concerns, and higher cost, the prescribing of clopidogrel-aspirin combination increased substantially during the study period. Quality improvement measures are warranted to educate physicians of the evidence regarding antiplatelet drugs for secondary stroke prevention and improve prescribing of safe antiplatelet drugs among IS patients.