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Triple antithrombotic therapy is commonly prescribed to patients undergoing percutaneous coronary intervention (PCI) who also have an indication for long-term anticoagulation, such as atrial fibrillation or a mechanical heart valve. This approach can, however, lead to an increased risk of bleeding. Omitting aspirin from the antithrombotic regimen has now been shown to reduce the incidence of bleeding events, without an overt increase in thrombosis. In their report, published in the Lancet, the WOEST study investigators view the reduction in bleeding complications in the trial as being “clinically meaningful”. On the basis of their findings, they propose that “aspirin does not need to be used in patients receiving oral anticoagulants and undergoing PCI”. However, in an accompanying Editorial, Professor Keith Fox (University of Edinburgh, UK), who was not involved in the study, cautions that “practice should not change on the basis of this study alone”.

The WOEST trial was designed on the basis of the hypothesis that inhibition of thrombin and P2RY12 with anticoagulants and clopidogrel, respectively, would render inhibition of prostaglandin G/H synthase 1 (cyclooxygenase 1) by aspirin less important. The trial was conducted between 2008 and 2011 at 15 treatment centres in Belgium and the Netherlands. The investigators enrolled a varied population of patients, stipulating only that they must be aged between 18 and 80 years, be scheduled to undergo PCI for a severe coronary lesion, and have a condition that required long-term anticoagulant therapy. Some exclusion criteria were specified, but the aim of the investigators was to replicate the real-world clinical situation to enable their findings to be generalized as widely as possible.

...much larger trials will be necessary to determine the right antithrombotic cocktail...

In addition to their anticoagulant medication, patients were randomly assigned to receive both clopidogrel and aspirin (triple therapy; n = 289) or clopidogrel alone (dual therapy; n = 284). During PCI, oral anticoagulants were continued when possible, or replaced with low-molecular-weight heparin at the discretion of the treating physician, and restarted after the intervention. The target international normalized ratio was determined on the basis of the patient's underlying condition. Patients who received a bare-metal stent took clopidogrel for between 1 and 12 months after PCI, whereas those who received a drug-eluting stent continued with clopidogrel for at least 12 months.

At 1-year follow-up, the incidence of all bleeding events was significantly reduced in patients receiving dual therapy compared with those receiving triple therapy (19.4% versus 44.4%; HR 0.36, 95% CI 0.26–0.50, P <0.0001). This outcome was driven by reductions in minimal and minor bleeding, as the incidence of major bleeding events did not significantly differ between the two groups. The incidence of multiple bleeding events (2.2% versus 12.0%) and the need for blood transfusion (3.9% versus 9.5%; OR 0.39, 95% CI 0.17–0.84, P = 0.011) was also lower for dual therapy than with triple therapy. These reduced rates of bleeding for dual therapy were consistent across patient subgroups. The findings for the secondary end point (a combination of death, myocardial infarction, stroke, target-vessel revascularization, and stent thrombosis) also favoured dual therapy (11.1% versus 17.6%; HR 0.60, 95% CI 0.38–0.94, P = 0.025). The rates of thrombotic events did not significantly differ between the two groups, although the investigators emphasize that the trial was not powered to assess this outcome.

Commenting on the WOEST study, Professor Deepak Bhatt from the Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA states “this was a cleverly designed and well-executed trial, [but] of course much larger trials will be necessary to determine the right antithrombotic cocktail for patients who have indications for both antiplatelet and anticoagulant therapy”. Professor Fox also calls for a judicious approach to these data, and believes that the WOEST study “provides an innovative stimulus, but one that requires confirmation” and reminds us that “the findings cannot be extrapolated to more-potent antiplatelet agents or novel anticoagulants”.