Investigators asked: What is the optimal therapy in patients requiring oral anticoagulation (OAC) who subsequently undergo coronary stenting? (Out of this question the investigators obtained the acronym WOEST.) The answer appears to be dual therapy without aspirin.

It's an important question for the growing number of older patients on OAC for AF or mechanical heart valves who then undergo coronary stenting. Until now, it really has not been clear what the optimal antithrombotic treatment should be. Lifelong anticoagulation is necessary, of course, for the prevention of stroke in patients with rhythm disturbances or with mechanical valves. When these patients undergo PCI with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. For these individuals, use of all three drugs (oral anticoagulants, aspirin, and clopidogrel) seems logical for the prevention of stroke and stent thrombosis.

It's also what the current ACC guidelines recommend: Following PCI or revascularization surgery in patients with AF, low-dose aspirin (<100 mg per day) and/or clopidogrel (75 mg per day) may be given concurrently with anticoagulation to prevent myocardial ischemic events.¹

The guidelines do acknowledge, though, that "these strategies have not been thoroughly evaluated and are associated with an increased risk of bleeding. (Level of Evidence: C)"

What is current clinical practice? Willem Dewilde, MD, and colleagues looked at this question in a 2012 survey of interventional cardiologists in eight European countries.² Triple therapy (warfarin, aspirin, and clopidogrel) was the most frequently prescribed (80%), generally for 1 month after bare-metal stenting (77%) and for at least 12 months after drug-eluting stent (60%) placement. Throughout triple therapy, interventional cardiologists surveyed reported the international normalized ratio (INR) was mostly targeted to the lower end of the therapeutic range (77%) in these patients on triple therapy; gastric protection was routinely prescribed (69%), mostly by giving proton-pump inhibitors (70%).

WOEST

WOEST was a study of 573 patients already treated with OAC for AF or mechanical valves and undergoing coronary stenting. Participants were prospectively randomized to two groups: one given additional clopidogrel only (double-therapy group) and the other given clopidogrel and aspirin (triple-therapy group). Each was followed for 1 year. The investigator-driven study was conducted in 15 hospitals in the Netherlands and Belgium, and was sponsored by the St. Antonius Hospital, Nieuwegein, The Netherlands.

As expected, OAC plus clopidogrel caused less bleeding than triple therapy (19.5% vs. 44.9%), but importantly there was no excess of thrombotic or thromboembolic events and actually a lower all-cause mortality with dual therapy.

According to Dr. Dewilde, TweeSteden Hospital, Tilburg, The Netherlands, "WOEST is the first study demonstrating that the omission of aspirin in patients treated with oral anticoagulants and having a coronary stent is safe. Omitting aspirin leads to less bleeding but does not increase the risk of stent thrombosis, stroke, or myocardial infarction. Although the number of patients in the trial is limited, this is an important finding with implications for future treatment and guidelines in this group of patients known to be at high risk of bleeding and thrombotic complications."

In "The Best of ESC Congress 2012" program, broadcast online 1 week after the meeting, it was noted that WOEST evaluated an important clinical area without a lot of evidence. Steen Dalby Kristensen, MD, DMSc, said, "It gives us important new information showing surprisingly—as a secondary endpoint—a reduction in mortality." While saying he would like to see more studies, Dr. Kristensen added "We would probably start using warfarin plus clopidogrel in some patients, but I don't think in all patients."

Interestingly, Kurt Huber, MD, from Vienna, Austira, noted that triple therapy is recommended for stable patients for only 3 to 6 months following drug-eluting stenting, but in this trial this therapy was used for 12 months, which might explain the high bleeding rates reported.

Professor Keith AA Fox, BSc, MB, ChB, from University of Edinburgh, United Kingdom, said even though the bleeding seen was of a more minor-to-moderate nature, "bleeding does impact outcome, so even a small increase in bleeding may be problematic." He added, "Watch this space, because in the future we may not automatically use aspirin in these patients."

References

1. Fuster V, Rydén LE, Cannom DS, et al. J Am Coll Cardiol 2011;57:e101-e198. http://content.onlinejacc.org/article.aspx?articleid=1144258
2. Rubboli A, Dewilde W, Huber K, et al. J Interv Cardiol 2012;25:163-9.

Keywords: Stroke, Myocardial Infarction, Drug-Eluting Stents, Belgium, Ticlopidine, Proton Pump Inhibitors, International Normalized Ratio, Thrombosis, Netherlands, Heart Valves, Hemorrhage

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