By Caroline Price, Senior medwireNews Reporter
Publication of the WOEST trial results reaffirm the study's major finding that antiplatelet therapy with clopidogrel alone is preferable to the use of both aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) who are receiving oral anticoagulant therapy.
The use of clopidogrel alone in this setting offers just as good protection against thrombotic events, but significantly reduces the risk for bleeding associated with the use of both antiplatelet therapies on top of oral anticoagulation, say the WOEST investigators.
The findings challenge the current European and US recommendation (based on expert opinion) that patients requiring PCI who are on long-term oral anticoagulant therapy, for example, because of a mechanical valve or atrial fibrillation, should receive triple therapy with aspirin, clopidogrel, and oral anticoagulation.
The WOEST (What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing) trial results were provisionally unveiled at the European Society of Cardiology Congress in September last year, and are now reported in full by investigators Willem Dewilde (Twee Steden Hospital, Tilburg, the Netherlands) and colleagues in The Lancet.
The trial included 573 patients (aged 18-80 years) with a long-term indication for oral anticoagulation and a severe coronary lesion (≥75% stenosis or fractional flow reserve <0.8) with indication for PCI. All patients received 75 mg clopidogrel daily and the 285 patients assigned to triple therapy group also received aspirin 80-100 mg daily.
Over the 1-year follow-up period, 54 (19%) patients in the double-therapy group reported any bleeding episode, compared with 126 (44%) patients in the triple-therapy group, translating into a significant 64% reduced risk for bleeding with double versus triple therapy. Just six (2%) patients receiving double therapy had multiple bleeding events, versus 34 (12%) of those receiving triple therapy. In line with these results, 11 (4%) double-therapy patients, compared with 27 (9.5%) triple-therapy patients required at least one blood transfusion, representing a 61% reduction in odds.
The improved bleeding rates did not appear to come at the cost of increased thrombotic events, however. Indeed, the secondary endpoint of death, myocardial infarction, stroke, target-vessel revascularization, and stent thrombosis was reached by a smaller proportion of patients in the double therapy group (11%) than in the triple therapy group (18%), but after correcting for imbalances in baseline characteristics the hazard for this combined endpoint was similar in each group.
The authors caution that the trial was small, and its open-label nature means it was open to inherent bias. Furthermore, they concede that the benefit in terms of bleeding with dual therapy was mainly due to a reduction in more minor bleeding events.
Nevertheless, the authors say the findings translate into a number needed to harm of 40, which they believe "is clinically relevant if all aspects of the effects of double therapy on bleeding risk are taken into account."
However, Keith Fox (University of Edinburgh, UK) argues in a related editorial that the WOEST trial involved a more aggressive antiplatelet regimen than is currently recommended, and would therefore be expected to be provoke a high rate of bleeding events. In addition, he says the study was underpowered to "resolve with confidence that there is no excess of stent thrombosis when aspirin is omitted."
Nevertheless he writes: "WOEST will certainly stimulate larger confirmatory trials with the aim of defining the optimum balance between too much and too little anticoagulant and antiplatelet therapy in patients who require both forms of treatment.
"Robust evidence shows that bleeding, especially major bleeding episodes, is hazardous, not only because of the bleeding event itself but also because of the consequences of bleeding, such as discontinuation of treatment leading to thrombotic complications."
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