Drop Aspirin in Stent Patients on Oral Anticoagulants: WOEST

August 28, 2012

August 28, 2012 (Munich, Germany) — Patients on oral anticoagulant therapy undergoing stenting should be treated with clopidogrel but not aspirin, according to the results of the What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulation and Coronary Stenting (WOEST) trial.

The trial, reported today at the European Society of Cardiology (ESC) 2012 Congress, showed a large reduction in overall TIMI bleeding in patients receiving dual therapy with oral anticoagulants and clopidogrel compared with those receiving triple therapy including aspirin. And efficacy did not seem to be compromised. If anything, there appeared to be lower rates of ischemic events and a significant reduction in all-cause mortality.

Although the study involved just 573 patients, as the first randomized trial to address this issue, it has been well received. Both cochairs of an ESC press conference at which WOEST was discussed said they thought the trial would be practice changing.

This is a huge deal.

Dr David Holmes (Mayo Clinic, Rochester, MN) said: "This is a huge deal. How to treat AF patients undergoing stenting is a huge clinical problem. These results have incredibly important clinical implications. They are going to change guidelines overnight."

Dr Keith Fox (University of Edinburgh, Scotland) commented: "If we look at the evidence prior to this, there has been very little. So this is a very big step. The community will take this seriously."

The oral anticoagulants used in the study were warfarin-type drugs. Holmes said it was not possible to extrapolate the results to the new anticoagulants at this stage in the absence of data.

Dr John Harold (Cedars-Sinai Heart Institute, Los Angeles, US), who is president-elect of the American College of Cardiology, commented to heartwire that WOEST was a "well-done study providing clinically relevant information." On the issue of whether it would change guidelines, he said: "The guideline process is very structured. This may take some time." He added: "Bleeding in patients on triple therapy is very prevalent. This is a real problem that we see every day, and this news will lead to some change of practice in the near term. It will also stimulate guideline committees to look at the data and decide whether updates are needed."

Too Small for Conclusions on Stent Thrombosis/Stroke

Harold cautioned, however, that the power of the study to look at clinical events was low. "The big worry is whether removing aspirin will lead to an increase in stent thrombosis and stroke. These data suggest not, but the numbers are too small for any conclusions to be drawn. This will be one of the questions raised on this study."

Dr Willem Dewilde

Presenting the trial, Dr Willem Dewilde (TweeSteden Hospital, Tilburg, the Netherlands) noted that oral anticoagulants are obligatory in most patients with AF and those with mechanical heart valves. Over 30% of these patients have concomitant ischemic heart disease, and when they undergo PCI, there is also an indication for aspirin and clopidogrel. While triple therapy is recommended in the guidelines, it is known to increase major bleeding, which could increase mortality, and there has been no prospective randomized data on the issue until now.

In the WOEST trial, 573 patients were randomized to dual therapy with oral anticoagulation and clopidogrel (75 mg daily) or to triple therapy with oral anticoagulation, clopidogrel, and aspirin 80 mg daily. Treatment was continued for one month after bare-metal stenting (35% of patients) and one year after drug-eluting-stent placement (65% of patients). Follow-up was for one year.

The primary end point of all TIMI bleeding was significantly reduced in the dual-therapy arm. This end point included minimal, minor, and major bleeding. Dewilde noted that there was a significant reduction in minimal and minor bleeding, and while major bleeding was also numerically lower, this did not reach statistical significance (p=0.159).

WOEST: Primary End Point--All Bleeding Events (TIMI Criteria)

  Dual therapy (%) Triple therapy (%) HR (95% CI) p
All bleeding events 19.5 44.9 0.36 (0.26–0.50) <0.001

Type of Bleeding Reduced

Type of bleeding Dual therapy (%) Triple therapy (%)
TIMI minimal 6.5 16.7
TIMI minor 11.2 27.2
TIMI major 3.3 5.8

Location of TIMI Bleeding: Worst Bleeding Per Patient

Location of bleeding Dual therapy (n) Triple therapy (n)
Intracranial 3 3
Access site 16 20
GI 8 25
Skin 7 30
Other 20 48

There was no difference in intracranial bleeding, with three cases in each group.

Dewilde noted that the trial was powered for superiority in bleeding, but it was not powered for noninferiority in efficacy. Clinical ischemic events were a secondary end point, and results suggested these were not increased by dropping aspirin. Indeed, most end points showed lower numerical rates in the dual-therapy arm, and total mortality was actually significantly reduced.

WOEST: Composite Efficacy End Point

  Dual therapy (%) Triple therapy (%) HR (95% CI) p
Composite efficacy end point 11.3 17.7 0.60 (0.38–0.94) 0.025

WOEST: Efficacy Results, Individual End points

End point Dual therapy (%) Triple therapy (%) p
Death 2.6 6.4 0.027
MI 3.3 4.7 0.382
Target vessel revascularization 7.3 6.8 0.876
Stroke 1.1 2.9 0.128
Stent thrombosis 1.5 3.2 0.165

Designated discussant of WOEST, Dr Marco Valgimigli (Ferrara, Italy), noted that the number need to treat to avoid a bleed by omitting aspirin was just four. While it was mostly minimal and minor bleeding that was reduced, he said, "These events are anything but minor from a clinical standpoint."

Holmes agreed with this, saying: "A reduction in minor bleeding is still very important. If you cut yourself shaving and you can't stop the bleeding, that can be a big deal."

Valgimigli noted that while the major bleeding reduction was not significant, the number needed to treat (by omitting aspirin) to avoid a major bleed was 40, and this may have become significant with larger numbers.

He added that the numerical reductions in stent thrombosis and stroke without aspirin were somewhat surprising and could either be a chance finding or could mean that bleeding is more important than antithrombotic effects for outcomes.