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Should patients on long-term warfarin take aspirin for heart disease?

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The literature on this topic is limited, but it suggests that the decision to prescribe aspirin to patients already taking warfarin (Coumadin) should be individualized. On one hand, the cardiovascular benefit of starting or continuing aspirin in patients already on warfarin outweighs the increased risk of bleeding in patients presenting with an acute coronary syndrome or those with mechanical heart valves or coronary stents. However, for patients with stable coronary artery disease or at risk of coronary disease, the benefit of adding aspirin is not substantial, and continuing warfarin alone may be the preferred strategy.

In patients with coronary artery disease, aspirin has been shown to reduce the rate of death due to all causes by about 18% and the rate of vascular events by about 25% to 30%.1,2 Warfarin is at least as effective as aspirin in reducing the rate of future cardiovascular events (especially if the target international normalized ratio [INR] is greater than 2.5), albeit with a higher bleeding risk.3–6

The decision to prescribe or continue aspirin in patients with coronary artery disease who also need long-term anticoagulation with warfarin for an unrelated medical problem, such as pulmonary emboli, requires careful assessment of the individual patient’s bleeding risk and cardiovascular benefit.

ESTIMATING THE BLEEDING RISK FOR PATIENTS ON WARFARIN

In patients taking warfarin, the risk of major bleeding (defined in most studies as hospitalization because of bleeding and requiring transfusion of at least two units of packed red cells, or an intracranial, intraperitoneal, or fatal bleeding episode) is reported to be about 2.0% to 3.8% per person-year.7–11 The risk of major bleeding with aspirin alone is estimated to be 0.13% per person-year,12 but when aspirin is combined with warfarin, the risk increases significantly.13 In a meta-analysis of randomized controlled trials,14 the risk of major bleeding was calculated to be about 1.5 times higher with combination therapy with aspirin and warfarin than with warfarin alone.

The individual’s bleeding risk depends on specific risk factors and the intensity of anticoagulation.15 The outpatient Bleeding Risk Index (BRI) can be used to estimate the bleeding risk for patients on warfarin.16 The BRI includes four risk factors for major bleeding, each scored as 1 point:

  • Age 65 or older
  • History of gastrointestinal bleeding
  • History of stroke
  • One or more comorbid conditions—recent myocardial infarction, anemia (hematocrit < 30%), renal impairment (serum creatinine level > 1.5 mg/dL), or diabetes mellitus.

The risk is low if the score is 0, moderate if the score is 1 or 2, and high if the score is 3 or more. In a validation study of the BRI, the rate of major bleeding was found to be 0.8%, 2.5%, and 10.6% per person-year on warfarin in the low, intermediate, and high-risk groups, respectively.17 In addition, compared with patients with a target INR of 2.5, those with a target INR higher than 3.0 have a higher frequency of bleeding episodes.10,15

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