August 28th, 2012

WOEST: Get Rid of the Aspirin in Triple Therapy

According to current guidelines and clinical practice, PCI patients already taking an oral anticoagulant generally end up on triple therapy comprising the anticoagulant plus clopidogrel and aspirin. However, there is no supporting evidence base for this approach, and the triple-therapy regimen is known to increase bleeding complications. Now a new study — the first randomized trial to address this situation, according to the investigators — may have a large impact on clinical practice by demonstrating that the omission of aspirin in this context appears to be safe and may reduce adverse events.

Results of the WOEST (What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting) trial were presented by Willem Dewilde at the ESC in Munich today. Investigators in the Netherlands and Belgium randomized 573 patients to triple therapy or dual therapy of an anticoagulant plus clopidogrel for at least 1 month after implantation of a bare-metal stent or 1 year after a drug-eluting stent. Two thirds of the patients were receiving oral anticoagulation for atrial fibrillation.

The primary endpoint, the incidence of all bleeding events, was dramatically reduced in the dual-therapy group at 1 year:

  • 44.9% with triple therapy versus 19.5% (HR 0.36, CI 0.26-0.50)

There were three intracranial bleeds in each group. Most of the difference in bleeding occurred in TIMI minor and minimal bleeding. The difference in TIMI major bleeding (3.3% vs. 5.8%) did not achieve statistical significance.

Clinical events, the trial’s secondary endpoint, were numerically lower in the dual-therapy group. The difference in mortality achieved statistical significance.

  • Mortality: 7 deaths (2.6%) with dual therapy versus 18 (6.4%) with triple therapy, p=0.027
  • MI: 3.3% versus 4.7%, p=0.382
  • TVR: 7.3% versus 6.8%, p=0.876
  • Stroke: 1.1% versus 2.9%, p=0.128
  • Stent thrombosis: 1.5% versus 3.2%, p=0.165

“The WOEST study demonstrates that omitting aspirin leads to less bleedings but does not increase the risk of stent thrombosis, stroke or myocardial infarction,” said Dewilde in an ESC press release. “Although the number of patients in the trial is limited, this is an important finding with implications for future treatment and guidelines in this group of patients known to be at high risk of bleeding and thrombotic complications.”

David Holmes said the trial addressed “an incredibly important issue” and predicted that it would “change the way we practice medicine, it will change practice right away.” Keith Fox said that the evidence base prior to WOEST was extremely limited and that the trial showed that there was no hazard in doing without aspirin. The ESC discussant, Marco Valgimigli, said the trial showed it was safe to drop aspirin and provided another demonstration that “we have hit the wall” with anticoagulation.

4 Responses to “WOEST: Get Rid of the Aspirin in Triple Therapy”

  1. Judith Andersen, AB, MD says:

    Extremely interesting : the decrease in bleeding is not unexpected, but the decreased mortality — given that the incidence of intracranial bleeds was similar and that of TIMI major bleeding not significantly different for dual and triple therapy — is counterintuitive. Like many issues in medicine — in which what seems obvious turns out to be unsupported by the facts, when they are finally known. Still, it will be interesting to dissect this study once published.

  2. Very much interesting, it appears that “less is more”. I am not sure if the full text is published yet but have a few questions and comments:

    1. How was the adherence to treatment in the triple therapy group?

    2. The reduced mortality is interesting but I look at it with caution. Was the study adequately powered to detect a mortality difference? According to the methods paper (, probably not.

    3. Moving from PCI to ACE management,is it time to revisit the use of aspirin as the cornerstone of ACS therapy? Several new antiplatelets or anticoagulants were challenged in recent trials because they were added on top of aspirin. Unsurprisingly, excess bleeding was a major drawback for all of them. Is it worth revisiting them, after omission of aspirin from the treatment regimen?

  3. Geoffrey Jao, MD says:

    This is a potentially practice-altering study hence the need to closely examine it thoroughly once it hits the press. Since the study’s primary endpoint is the incidence of all bleeding events, I would be interested to know if the bleeding risk of the comparison groups similar, which oral anticoagulants were used (i.e., any of the newer agents), if warfarin was used, what proportion of patients had therapeutic INRs, was a subgroup analysis done to look at those patients with INR in the 2-2.5 range?

    With regard the secondary endpoints, I echo the above comments about whether the study is powered to detect changes in mortality, stroke, MI, TVR, or stent thrombosis. How long was the study duration follow-up?

    Overall, the study is a timely piece that addresses a common clinical dilemma encountered especially among elderly patients who are predisposed to both CAD and afib but is also more prone to bleeding complications. The authors should be congratulated for tackling this problem and provide some guidance on the right thing to do.

  4. Mani Prasad Gautam, MD says:

    Nice study and will have an impact in clinical practice. But few issues are unexplained, may need to go through the whole publication.
    1. What is the reason for increased mortality? As there is no difference in the incidence of stroke, major bleeding and MI incidence, raised mortality in triple therapy group seems ellusive.
    2. Although the p value is not significant, Why there should be increased trend to stent thrombosis in triple therapy group? Contradictory to this point, on the otherside, why there is decreased TVR in triple therapy regime?
    3. What happens if we use Warfarin and Aspirin in post PCI cases of CAD with AF in place of Warfarin and Clopidogrel? As Aspirin is much cheaper than Clopidogrel.