Elsevier

The Lancet

Volume 381, Issue 9872, 30 March–5 April 2013, Pages 1107-1115
The Lancet

Articles
Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

https://doi.org/10.1016/S0140-6736(12)62177-1Get rights and content

Summary

Background

If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin.

Methods

We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938.

Findings

573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26–0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17–0·84, p=0·011).

Interpretation

Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events.

Funding

Antonius Ziekenhuis Foundation, Strect Foundation.

Introduction

Long-term treatment with oral anticoagulants is necessary in patients with mechanical heart valves and in most with atrial fibrillation.1, 2, 3 20–30% of patients have concomitant ischaemic heart disease that requires percutaneous coronary intervention (PCI) with stenting.3, 4 In these cases, double antiplatelet therapy with aspirin and clopidogrel is indicated to prevent stent thrombosis.3, 5 The combination of oral anticoagulants and antiplatelet therapy, however, is associated with a high annual risk (4–16%) of fatal and non-fatal bleeding episodes.4, 6, 7, 8 The optimum treatment after PCI is, therefore, unclear when thrombotic and bleeding risks are both taken into account. No indicative data are available from prospective randomised trials. Experts recommend triple antithrombotic therapy, consisting of oral anticoagulants with a revised target international normalisation rate, aspirin, and clopidogrel (for as short a time as possible),3 but this strategy has not been tested prospectively.3, 9 Omission of oral anticoagulants could lead to an increased risk of thrombotic stroke,10, 11, 12 whereas clopidogrel is essential to prevent stent thrombosis.6, 13, 14, 15 The exclusion of aspirin might, therefore, be useful to reduce the bleeding risk in patients with coronary artery disease. Results from two large, randomised trials showed that full-intensity oral anticoagulants alone after myocardial infarction were associated with reduced rates of reinfarction and stroke compared with aspirin, although the risk of bleeding episodes was raised.16, 17

In this trial we tested the hypothesis that in patients taking oral anticoagulants and undergoing PCI, the use of clopidogrel alone would reduce the risk of bleeding but not increase the risk of thrombotic events compared with clopidogrel plus aspirin.

Section snippets

Study design and patients

The What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing (WOEST) study was an open-label, randomised, controlled trial done at 15 sites in the Netherlands and Belgium.18 All eligible patients referred to the study centres from November, 2008, to November, 2011, were included. Inclusion criteria were a long-term indication for oral anticoagulation treatment (until at least 1 year after the study); a severe coronary lesion (at

Results

573 patients were enrolled, of whom 284 were assigned to the double-therapy group and 289 to the triple-therapy group (figure 1). Baseline and procedural characteristics were similar in the two groups (Table 1, Table 2). Complete follow-up was obtained for 98·3% of the patients (figure 1). The final collection of follow-up data occurred on Aug 1, 2012. The median follow-up for both groups was 365 days, and the mean follow-up was 358 (minimum 16 and maximum 365) days for the double-therapy group

Discussion

The WOEST trial clearly shows that clopidogrel alone administered to patients taking oral anticoagulants who require PCI is associated with a significantly lower rate of bleeding complications at 1 year than is use of clopidogrel plus aspirin.

As anticipated, the frequency of gastrointestinal bleeding episodes was substantially lower in the double-therapy than in the triple-therapy group, which is probably related to the local erosive effect of aspirin. When assessed by the BARC criteria, the

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