What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing - WOEST

Description:

The goal of the trial was to evaluate treatment with clopidogrel alone compared with aspirin and clopidogrel among patients on oral anticoagulation therapy undergoing percutaneous coronary intervention (PCI).

Hypothesis:

Clopidogrel alone would be superior at reducing the incidence of bleeding without increasing thrombotic events.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Age 18-80 years
  • Indication for oral anticoagulation therapy
  • Indication for PCI (fractional flow reserve <0.8 or coronary stenosis ≥75%)

    Number of enrollees: 573
    Duration of follow-up: 1 year

Exclusions:

  • History of intracranial hemorrhage
  • Cardiogenic shock
  • Contraindication to aspirin or clopidogrel
  • Peptic ulcer in the last 6 months
  • Thrombocytopenia
  • Major bleeding (TIMI) in the last 12 months
  • Pregnancy

Primary Endpoints:

  • Any bleeding event

Secondary Endpoints:

  • Death, MI, stroke, stent thrombosis, or TVR

Drug/Procedures Used:

Patients in the Netherlands and Belgium on oral anticoagulation therapy, due to atrial fibrillation or mechanical heart valve, undergoing PCI, were randomized to clopidogrel alone (n = 284) versus aspirin 80 mg and clopidogrel (n = 289).

Patients were loaded with clopidogrel (300 mg 24 hours before or 600 mg 4 hours before PCI) or received clopidogrel 75 mg daily for at least 7 days before PCI. During PCI, anticoagulation therapy was maintained where possible with a target international normalized ratio (INR) of 2.0.

The study drug was maintained for 1 month after a bare-metal stent and 1 year after a drug-eluting stent.

Principal Findings:

Overall, 573 patients were randomized. The mean age was 70 years, 77% were men, mean body mass index was 28 kg/m2, mean ejection fraction (EF) was 46%, 25% had an acute coronary syndrome at baseline, 73% had femoral access, 24% had diabetes, 34% had a history of myocardial infarction (MI), and 18% had a history of renal failure. The indication for anticoagulation was atrial fibrillation in 69%, mechanical valve in 10%, or apical aneurysm, pulmonary embolism, peripheral arterial disease, or left ventricular EF <30% in 20%. Approximately one-third of patients (32%) received a bare-metal stent and two-thirds (65%) received a drug-eluting stent.

The primary outcome, any bleeding event at 1 year, occurred in 19.4% of the double therapy group versus 44.4% of the triple therapy group (p < 0.001). The primary outcome was the same among all tested subgroups.

- TIMI major and minor: 14.0% vs. 31.3% (p < 0.0001); TIMI major: 3.2% vs. 5.6% (p = 0.16), respectively, for clopidogrel alone vs. aspirin and clopidogrel

- GUSTO severe and moderate bleeding: 5.4% vs. 12.3% (p = 0.003); GUSTO severe: 1.4% vs. 3.5% (p = 0.12), respectively, for clopidogrel alone vs. aspirin and clopidogrel

- Any blood transfusion: 3.9% vs. 9.5% (0.011), respectively

Location of worst bleeding event:
- Intracranial: 1% vs. 1%
- Access site: 6% vs. 7%
- Gastrointestinal: 3% vs. 9%
- Skin: 3% vs. 1%
- Nose: 4% vs. 7%, respectively, for clopidogrel alone versus aspirin and clopidogrel

- Death, MI, stroke, stent thrombosis, or target vessel revascularization (TVR): 11.1% vs. 17.6% (p = 0.025)
- All-cause death: 2.5% vs. 6.3% (p = 0.027)
- MI: 3.2% vs. 4.6% (p = 0.38)
- TVR: 7.2% vs. 6.7% (p = 0.88)
- Stroke: 1.1% vs. 2.8% (p = 0.13)
- Stent thrombosis: 1.4% vs. 3.2% (p = 0.17), respectively, for clopidogrel alone vs. aspirin and clopidogrel

Interpretation:

Among patients on oral anticoagulation therapy undergoing PCI, the use of clopidogrel alone compared with aspirin plus clopidogrel reduced the frequency of all bleeding events. This was accomplished without an increase in adverse ischemic events. The primary outcome was mainly driven by a reduction in minimal bleeding events, which may not be clinically important. Although the observed reduction in mortality is plausible, this trial was not powered to show a mortality difference; therefore, this outcome should be interpreted with caution. Minimization of bleeding events after PCI is an important priority; however, additional studies (placebo controlled) are needed before this strategy can be widely adopted.

References:

Dewilde WJ, Oirbans T, Verheugt FW, et al., on behalf of the WOEST Investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013;381:1107-1115.

Presented by Dr. W. Dewilde at the European Society of Cardiology Congress, Munich, Germany, August 28, 2012.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Vascular Medicine

Keywords: Follow-Up Studies, Platelet Aggregation Inhibitors, Peripheral Arterial Disease, Ticlopidine, Purinergic P2Y Receptor Antagonists, International Normalized Ratio, Blood Transfusion, Coronary Stenosis, Thrombosis, Heart Valves, Stroke, Myocardial Infarction, Acute Coronary Syndrome, Drug-Eluting Stents, Pulmonary Embolism, Belgium, Percutaneous Coronary Intervention, Renal Insufficiency, Body Mass Index, Metals, Netherlands, Atrial Fibrillation, Diabetes Mellitus


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