SNOWMASS, COLO. – A patient on chronic warfarin for atrial fibrillation experiences an acute coronary syndrome and gets a coronary stent. What antiplatelet regimen will you prescribe to protect against potentially catastrophic stent thrombosis?
The first-ever randomized trial-based guidance regarding this common and vexing clinical scenario has been provided by the European WOEST (What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting?) trial. The study demonstrated that warfarin plus clopidogrel was superior to warfarin and dual antiplatelet therapy (DAPT) with clopidogrel plus low-dose aspirin, both in terms of bleeding events and 1-year all-cause mortality, Dr. Spencer B. King III observed at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.
Dr. Patrick T. O'Gara
"This trial was very impressive. It will be interesting to see how this is handled here in this country. We’ll see how this evolves as guidelines continue to reflect new evidence," said Dr. King, president of the Saint Joseph’s Heart and Vascular Institute and professor of medicine emeritus at Emory University, Atlanta. The trial results were presented at last year’s European Society of Cardiology meeting.
Current ACC/American Heart Association guidelines covering this scenario recommend warfarin at a target INR of 2.0-2.5, 1 year of a potent antiplatelet agent such as clopidogrel, and low-dose aspirin indefinitely. But that’s based upon expert opinion established in the pre-WOEST days, noted Dr. King, who was not involved in WOEST.
In the multicenter WOEST trial, 573 Dutch or Belgian coronary stent recipients on chronic warfarin remained on the anticoagulant and were randomized to DAPT with 75 mg/day of clopidogrel and 80 mg/day of aspirin or to clopidogrel only.
The primary study endpoint, consisting of the cumulative 1-year incidence of all TIMI bleeding events, occurred in 44.9% of patients on triple therapy (warfarin plus DAPT), compared with 19.5% on double therapy with warfarin and clopidogrel. This translated to a highly significant 64% relative risk reduction (P less than .001).
Dr. Spencer B. King III
All-cause mortality, one of two secondary endpoints, occurred in 6.4% of patients on triple therapy, significantly more than the 2.6% rate in patients on double therapy. The composite secondary endpoint, comprising death, MI, stroke, stent thrombosis, or target vessel revascularization, occurred in 24% of patients on triple therapy compared to 15.8% on double therapy without aspirin. Of note, the stent thrombosis rate was 1.5% on double therapy versus 3.2% with triple therapy, Dr. King continued.
He added that the current standard recommendation for 12 months of DAPT following stent implantation, a consistent feature in the European Society of Cardiology, American College of Chest Physicians, and ACC/AHA guidelines, is open to question. That’s because the risk of stent thrombosis is greatest in the month or so following stent placement, then drops off sharply. Yet the bleeding risk associated with DAPT remains elevated so long as the patient remains on the regimen.
Incoming ACC President Dr. Patrick T. O’Gara, lead author of the 2013 ACC/AHA Guidelines for the Management of ST-Elevation Myocardial Infarction, confirmed that the recommendation for 12 months of DAPT in stent recipients is based upon expert consensus rather than data from prospective randomized trials, which were nonexistent at the time. This consensus opinion went well beyond the recommended 6 months of clopidogrel advised by the drug’s manufacturer at the time the potent antiplatelet agent won Food and Drug Administration marketing approval.
"I think it’s interesting that we have adopted this recommendation for 12 months of dual antiplatelet therapy, but now we’re reexamining the efficacy beyond 6 months in multiple trials," said Dr. O’Gara, executive medical director of the cardiovascular center at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
Neither Dr. O’Gara nor Dr. King reported having any relevant financial interests.