CORONOR Registry: Long-term Warfarin Plus Antiplatelet Increases Bleeding in Stable CAD Patients

Download this article's Factoid (PDF & PPT for Gold Subscribers)  

The combination of warfarin and antiplatelet therapy can put patients with stable coronary artery disease (CAD) at increased risk for major bleeding while providing no added protection against ischemic events, according to registry data published in the October 7, 2014, issue of the Journal of the American College of Cardiology. Major bleeding, through rare, carried a risk of death.

Major Bleeding Uncommon, But Deadly

At 2-year follow-up, the rate of major bleeding was 0.6% per 100 patient-years (51 events). Most were BARC type 3a bleeds, and 12 were fatal. In more than half of cases (54.9%), the site of bleeding was gastrointestinal. Even after adjustment for clinical characteristics, major bleeding was associated with increased mortality (adjusted HR 2.89; 95% CI 1.73-4.83; P < .0001).

Multivariable analysis identified 4 independent predictors of major bleeding (table 1).

Table 1. Predictors of Major Bleeding in Stable CAD

 
Additionally, bleeding was greatly increased in patients taking a combination of antiplatelet therapy and vitamin K antagonists compared with those who received vitamin K antagonists alone, dual antiplatelet therapy, or antiplatelet monotherapy (log rank P < .0001). The adjusted HR for bleeding in the combined antiplatelet and vitamin K group was 7.30 (95% CI 3.91-13.64) compared with antiplatelet monotherapy. In contrast, there was no difference in the risk of cardiovascular death, MI, or nonhemorrhagic stroke between patients receiving vitamin K antagonists plus antiplatelet therapy and those on vitamin K antagonists alone (P = .697).

The study authors point out that the results are not generalizable to all stable CAD patients since anticoagulant therapy was limited to vitamin K antagonists and antiplatelet agents were limited to aspirin and/or clopidogrel. Furthermore, because the study focused on BARC ≥ 3 bleeds, less severe events that could be associated with the prognosis were not analyzed.

“For the clinician, the important message is to avoid long-term use of antiplatelet agents in combination with oral anticoagulation in stable CAD patients and to consider coprescription of a proton-pump inhibitor because many events in these patients are related to gastrointestinal bleeding,” Dr. Bauters and colleagues write.

Lessons for Clinicians

In an editorial accompanying the study, Harold L. Dauerman, MD, of the University of Vermont College of Medicine (Burlington, VT), points out that the study “provides the first point estimates of BARC bleeds in the outpatient setting” and notes that the findings are consistent with major bleeding seen in ACS patients.

“The CORONOR registry suggests that warfarin does not confer a bleeding risk; rather, the combination of antiplatelet therapy with warfarin is the only antithrombotic regimen that independently predicts bleeding,” he writes. “Importantly, continuing aspirin with warfarin does not demonstrate ischemic benefit.”

Dr. Dauerman says the message to clinicians from this and at least 4 other studies is “stop worrying about platelet inhibition in patients with CAD who are taking oral anticoagulant agents.”

In his own practice, Dr. Dauerman plans to continue giving aspirin to many stable CAD patients with A-fib, particularly those with first-generation DES. However, in selected stable CAD patients with A-fib identified by CORONOR as being at high bleeding risk, he says, “these registry observations will be heeded: stop the aspirin, continue the warfarin, and use the art of clinical medicine to guide decisions where clear information remains wanting.”

Sources:
1. Hamon M, Lemesle G, Tricot O, et al. Incidence, source, determinants, and prognostic impact of major bleeding in outpatients with stable coronary artery disease. J Am Coll Cardiol. 2014;64:1430-1436.

2. Dauerman HL. Reconsidering the necessity of aspirin in stable coronary artery disease [editorial]. J Am Coll Cardiol. 2014;64:1437-1340.

Disclosures:

• Dr. Bauters reports no relevant conflicts of interest.
• Dr. Dauerman reports serving as a consultant for Medtronic and The Medicines Company and receiving research grants from Abbott Vascular and Medtronic.

Related Stories:

• CORONOR Registry: No Advantage to Prolonged DAPT in Stable CAD
• Danish Registry Suggests Aspirin Unnecessary in A-fib Patients After MI or PCI
• WOEST: Clopidogrel Alone Works Best for PCI Patients on Oral Anticoagulants