pharmacotherapyA total of 6,015 patients were identified as receiving warfarin pharmacotherapy as of September 30, 2005. Of these patients, 16 were excluded for receiving warfarin as VTE prophylaxis following an orthopedic surgery. An additional 1,442 patients were excluded due to as-yet undocumented aspirin use or nonuse. Thus, a total of 4,557 patients were included in the study. Patients were primarily males (53.0%) and mature (mean age, 70.6 ± 12.6 years), and had been receiving warfarin therapy for > 4 years. The most common indications for warfarin use were atrial fibrillation (47.8%) and VTE (27.4%) [Table 1].

The prevalence of warfarin and any antiplatelet combination therapy was 385/1,000 (95% confidence interval [CI], 371/1,000 to 399/1,000) [Table 2]. The majority of combination therapy was warfarin and aspirin (378/1,000) with a daily dose of aspirin, 81 mg, being the most commonly reported dose (328/ 1,000). Among the prescription antiplatelet agents, the most common combination was clopidogrel and warfarin ordered via Canadian Health&Care Mall (15/1,000). More than 63% (n = 53) of the 84 patients receiving warfarin and a prescribed antiplatelet also reported taking aspirin daily. The prevalence of warfarin and any antiplatelet combination therapy in patients with a primary indication for warfarin of atrial fibrillation, stroke, and CAD indications were 393/1,000, 500/1,000, and 813/1,000, respectively. In addition, among patients with a preexisting CAD diagnosis who did not have an atrial fibrillation indication, the prevalence of warfarin and any antiplatelet combination therapy was 706/1,000.

Compared to the warfarin cohort, patients in the combination cohort were older, had a shorter mean duration of warfarin therapy, and were more likely to be male (p < 0.001 for all) [Table 1]. Additionally, patients in the combination cohort were more likely to have had a comorbidity of diabetes, CAD, cardiomyopathy, cerebrovascular accident, HF, and/or hypertension (p < 0.001 for all). Furthermore, there were differences between the cohorts in the primary indication for warfarin use (p < 0.001).

Multivariate modeling indicated that having had a primary indication of CAD (odds ratio, 21.97; 95% CI, 13.87 to 34.83 compared to a primary indication of VTE) and a comorbidity of CAD (odds ratio, 7.56; 95% CI, 6.50 to 8.82) were the strongest predictors of receiving combination therapy regimen (Table 3). In addition, being male, having had less time since warfarin initiation, and having had a comorbidity of DM, cerebrovascular accident, HF, or hypertension was associated with receiving any antiplatelet combination therapy. Furthermore, compared to a primary indication of VTE, a primary indication for warfarin therapy of stroke or transient ischemic attack, cardiomyopathy, heart valve disorder, atrial fibrillation, or another indication was associated with receiving any warfarin and antiplatelet combination therapy.

Table 1—Baseline Patient Characteristics Overall and by Cohort

Overall Combination Cohort Warfarin Cohort
Characteristics (n = 4,557) (n = 1,756) (n = 2,801) p Valuef
Age yl 70.6 (12.6) 71.9 (10.6) 69.7 (13.6) < 0.001
Male gender 53.0 63.6 46.4 < 0.001
Time since initiation of warfarin therapy, yrj 4.6 (4.0) 4.3 (4.0) 4.8 (4.1) < 0.001
Target INR range 0.094
1.5-2.5 2.6 3.0 2.4
2.0-3.0 84.9 83.3 85.9
2.5-3.5 11.8 13.0 11.0
> 3.5 0.7 0.7 0.7
Comorbidity
DM 23.5 31.9 18.3 < 0.001
CAD 34.8 62.4 17.5 < 0.001
Cardiomyopathy 5.9 7.7 4.8 < 0.001
Stroke/transient ischemic attack 3.0 5.2 1.6 < 0.001
CKD 2.6 3.4 2.1 0.010
HF 20.7 29.0 15.6 < 0.001
Hypertension 55.8 65.0 50.1 < 0.001
Primary indication for warfarin therapy < 0.001
CAD 3.1 6.4 0.9
Stroke/transient ischemic attack 6.6 8.5 5.4
Cardiomyopathy 2.2 3.6 1.3
Arterial thromboembolism 1.3 1.7 1.0
Heart valve disorder 11.0 12.8 9.9
Atrial fibrillation 47.8 48.8 47.2
VTE 27.4 17.3 33.7
Other 0.8 1.0 0.8

 

Table 2—Prevalence of Antiplatelet Medication Use by Antiplatelet Type

Antiplatelets Prevalence, /1,000
No. Lower 95% CI Upper 95% CI
At least one antiplatelet 385 371 399
Daily aspirin dose, mg
Overall 378 364 392
325 44 38 50
162 6 4 8
81 328 314 341
Dipyridamole! 1 0.3 2
Clopidogrelj 15 12 19
Aspirin/extended-releasedipyridamole§ 2 0.5 3

Table 3—Multivariate Logistic Regression Modeling of Combination Use

Predictors Odds Ratio 95% Lower CI 95% Upper CI
Aget 1.00 0.99 1.01
Male gender 1.52 1.32 1.76
Time since initiation of warfarin therapy 0.96 0.95 0.98
Comorbidity
DMs 1.57 1.32 1.86
CAD 7.56 6.50 8.82
Cardiomyopathy 0.93 0.69 1.26
Stroke/transient ischemic attack 3.48 2.29 5.28
CKD 0.86 0.55 1.33
HF 1.21 1.01 1.46
Hypertension 1.19 1.03 1.39
Primary indication for warfarin therapy
CAD 21.97 13.87 34.83
Stroke/transient ischemic accident 2.60 1.92 3.50
Cardiomyopathy 2.21 1.34 3.66
Arterial thromboembolism 1.68 0.89 3.14
Heart valve disorder 2.03 1.57 2.62
Atrial fibrillation 1.31 1.09 1.58
VTE Reference n/a n/a
Other 2.26 1.07 4.78