The Prevalence and Risks of Inappropriate Combination of Aspirin and Warfarin in Clinical Practice: Results From WARFARIN-TR Study (original) (raw)
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Inappropriate combination of warfarin and aspirin
The Anatolian Journal of Cardiology, 2015
Objective: A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). Methods: This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Results: Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). Conclusion: The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.
European Heart Journal, 2004
To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI). Patients who were hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed according to the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow-up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently withdrawn as opposed to 14.0% in the aspirin group (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). Analyses were performed on an intention-to-treat basis. The combination of cardiovascular death, reinfarction or stroke was registered in 28.1% in the aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin group (NS). Whereas no difference was found with regard to total mortality or reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006). A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding.
Should aspirin be continued in patients started on warfarin?
Journal of General Internal Medicine, 2004
Clinicians frequently face the decision of whether to continue aspirin when starting patients on warfarin. We performed a meta-analysis to characterize the tradeoffs involved in this common clinical dilemma.
Circulation, 2002
; for the Combination Hemotherapy and Mortality Prevention (CHAMP) Study Group* Background-Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results-We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank Pϭ0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank Pϭ0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank Pϭ0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; PϽ0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. Conclusions-In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy. (Circulation. 2002;105:557-563.
Circulation, 2002
for the Combination Hemotherapy and Mortality Prevention (CHAMP) Study Group* Background-Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results-We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank Pϭ0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank Pϭ0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank Pϭ0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; PϽ0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. Conclusions-In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy. (Circulation. 2002;105:557-563.)
2006
Aims In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (AþW) with aspirin alone in such patients. Methods and results MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), AþW did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90-1.03), P ¼ 0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47-2.13), P , 0.00001. However, in studies with INR of 2-3, AþW was associated with a significant reduction of MAE [OR 0.73 (0.63-0.84), P , 0.0001, number needed to treat to avoid one MAE ¼ 33], albeit at an increased risk of MB [OR 2.32 (1.63-3.29), P , 0.00001; number needed to harm by causing one MB ¼ 100]. In both analyses, intracranial bleeding was not significantly increased by AþW when compared with aspirin alone. Conclusion For patients recovering from ACS, a combined strategy of AþW at INR values of 2-3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a 'double' anti-platelet strategy or to newer evolving treatments warrants further investigation.
Journal of Korean medical science, 2010
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase > or =15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of > or =15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respec...
2006
BACKGROUND: Despite the risk of hemorrhage, warfarin is the most commonly used oral anticoagulant today, both as monotherapy and when taken in combination with selected drugs. Warfarin is used most commonly for irregular heartbeat, after a heart attack, and after joint or heart valve replacement surgery. OBJECTIVE: To evaluate the relative risk of hemorrhage in health plan members who received warfarin concomitant with a drug known to cause an interaction or after diagnosis of liver disease or heart failure (HF). METHODS: A cohort study sample was drawn from an administrative database comprising medical and pharmacy claims for 1.7 million health plan members. A health plan member was defined as anyone who was eligible for pharmacy and medical benefits at any time from October 1, 2003, to September 30, 2004. To be included in the study, a member must have received at least 1 pharmacy claim for warfarin during the study period and been younger than 100 years. Hemorrhage was defined as...