MD Conference Express ESC 2012 - (Page 14)
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C L I N I C A L
T R I A L
H I G H L I G H T S
Long-term OAC therapy is necessary in most patients with atrial fibrillation (AF) or a mechanical heart valve. The addition of aspirin and clopidogrel are indicated when these patients undergo percutaneous coronary intervention (PCI), but when all 3 drugs are coadministered, the risk of major bleeding is substantially increased [Sorensen et al. Lancet 2009]. In this context, the What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulation and Coronary Stenting [WOEST; NCT00769938] trial was designed to test the hypothesis that in patients on OAC therapy undergoing PCI, the addition of clopidogrel alone is superior to the combination of aspirin and clopidogrel with respect to bleeding. The results of the trial were presented by Willem Dewilde, MD, Twee Steden Hospital, Tilburg, the Netherlands. WOEST was an investigator-initiated, prospective, randomized study conducted in 15 Danish and Belgium hospitals between November 2008 and November 2011. Patients with a prior history of AF (69%), a mechanical heart valve (10%), or other indication for OAC (eg, thromboembolic disease or severe systolic heart failure) were openly randomized to either dual (warfarin+clopidogrel 75 mg QD; n=279) or triple (warfarin+clopidogrel 75 mg QD+aspirin 80 mg QD; n=284) therapy. Patients were treated with clopidogrel for a minimum of 1 month after placement of a bare-metal stent (~30% of patients) and 1 year after placement of a drug-eluting stent (~65%). All patients were followed for 1 year. The primary outcome was the occurrence of any bleeding event (Thrombolysis in Myocardial Infarction [TIMI] major or minor criteria), and the study was statistically powered to detect a 60% reduction in bleeding based on prior cohort data (annual expected bleeding rate on triple therapy was projected to be 12%). Secondary exploratory endpoints included ischemic events, a combination of stroke, death, myocardial infarction (MI); stent thrombosis (ST) and target vessel revascularization (TVR); and individual components of these endpoints [Dewilde W and Berg JT. Am Heart J 2009]. Baseline characteristics in the WOEST study revealed the mean age of patients was ~70 years, ~80% were men, ~70% had a history of hypertension, 70% had hypercholesterolemia, and 25% to 30% had a prior history of either diabetes, MI, or heart failure. Concurrent use of proton pump inhibitors was ~35%. Despite the exclusion of patients with a recent history of major bleeding, peptic ulcer disease, or other major risk factors, bleeding in this study was higher than expected (~45% of patients assigned to triple therapy experienced a bleeding endpoint within 1 year). However, patients treated with dual therapy experienced significantly less bleeding compared with triple therapy (19.5% vs 44.9%; HR, 0.36; 95% CI, 0.26 to 0.50; p<0.001; Figure 1).
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Figure 1. Primary Endpoint: Total Number of Bleeding Events (TIMI Criteria).
50% Triple Therapy Group
44.9%
Cumulative Incidence of Bleeding
40%
30%
20% Dual Therapy Group 10%
p<0.001 HR=0.36 (95%CI, 0.26 to 0.50)
19.5%
0%
0
30
60
90 120
180 Days
270
365
No. at Risk 284 210 194 186 279 253 244 241
181 241
173 236
159 226
140 208
TIMI=thrombolysis in myocardial infarction. Reproduced with permission from W. Dewilde, MD.
Results were consistent among major subgroups, including when analyzed by a threshold age of 75 years, gender, presentation with acute coronary syndrome, indication for OAC, and stent received. The difference in bleeding between the 2 treatment groups was driven predominantly by TIMI minimal and minor bleeding from the access site, gastrointestinal, and superficial locations. There was no difference between the 2 groups in TIMI major bleeding (3.3% vs 5.8%; p=0.159) or intracranial bleeds (3 in each group). Patients receiving dual therapy experienced significantly fewer composite ischemic events compared with those receiving triple therapy (11.3% vs 17.7%; HR, 0.60; 95% CI, 0.38 to 0.94; p=0.025). Each component of the composite ischemic endpoint was consistently less frequent among patients assigned dual therapy except for TVR. The investigators concluded that a strategy of omitting aspirin is an option in high-risk patients on chronic anticoagulation undergoing PCI. Although it was an openlabel study, this provocative trial will hopefully open the door for further investigations of the optimal long-term treatment strategy to balance ischemic and bleeding outcomes in high-risk patients.
Results from the Aldo-DHF Trial
Written by Maria Vinall
Results from the Aldosterone Receptor Blockade in Diastolic Heart Failure [Aldo-DHF; ISCRTN94726526] trial, presented by Burkert Mathias Pieske, MD,
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Table of Contents for the Digital Edition of MD Conference Express ESC 2012
MD Conference Express ESC 2012
Contents
ESC 2012 Clinical Practice Guidelines
TAVI: 10 Years After the First Case
PARAMOUNT Trial Results
TRILOGY ACS Outcomes
Results from the ALTITUDE Trial
Results of the WOEST Trial
Results from the Aldo-DHF Trial
FAME 2 Results
Results from the IABP-SHOCK II Trial
STEMI Mortality Decreases in France While Some Key Risk Factors Increase
Results from the PURE Study
PURE: Treatment and Control of Hypertension
Genetic Determinants of Variability in Dabigatran Exposure
The RE-LY AF Registry
TRA 2°P-TIMI 50 Results
Rivaroxaban of Benefit in STEMI: ATLAS ACS 2-TIMI 51
Ivabradine Effect on Recurrent Hospitalization for HF
CLARIFY: Similar 1-Year Outcomes for Men and Women with Stable CAD
HPS2-THRIVE Study Results
PRoFESS Study Results
Outcomes from the CARDia Trial
Hypertension
Atrial Fibrillation
Heart Failure
MD Conference Express ESC 2012
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