my personal edition > cardiology other > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Severe Bleeding Rate With Clopidogrel/Aspirin Comparable to That of Warfarin: Presented at AHA

By Emma Hitt, PhD

ORLANDO, FL -- November 6, 2007 -- The rate of severe bleeding with the combination of clopidogrel and aspirin in patients at high cardiovascular risk is 1.8% per year, which is comparable to the rate observed with long-term warfarin therapy in patients with atrial fibrillation, according to an analysis of several clinical trials.

Freek W Verheugt, MD, Professor, Department of Cardiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands, presented the results of the analysis here on November 5 at the American Heart Association (AHA) 2007 Scientific Sessions.

Dr. Verheugt and colleagues compiled results from four large trials -- CURE, CREDO, MATCH and CHARISMA* -- to determine the annual rate of severe bleeding with the combination of clopidogrel and aspirin. The studies comprised 40,707 patient-years overall.

The bleeding rate was also determined for warfarin in three major observational trials of warfarin in patients with atrial fibrillation -- SPAF-III, SPORTIF III and SPORTIF V* -- which included 11,921 patient-years.

Over the four dual antiplatelet trials, therapy resulted in an average bleeding rate of 1.8% compared with the trials of warfarin, which showed a bleeding rate of 2.5%. However, patients in the dual antiplatelet trials were younger than those in the warfarin trials (64 vs 71 years).

The researchers then compared the clopidogrel/aspirin and warfarin trials with the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events - W (ACTIVE-W) randomized trial which assessed clopidogrel/aspirin versus warfarin in patients with documented atrial fibrillation. That trial found and incidence of bleeding of 2.4% with clopidogrel/aspirin and 2.2% for warfarin. Thus, the rate of bleeding was actually slightly higher for the clopidogrel/aspirin combination when the two were compared directly.

"Long-term combination therapy with clopidogrel/aspirin in cardiovascular patients is associated with a severe bleeding rate, which comes close to that of chronic warfarin therapy in atrial fibrillation," the authors concluded.

They added that physicians "should also be aware of the enhanced risk with long-term dual antiplatelet therapy, especially when using drug-eluting stents."

According to Dr. Verheugt, one way to minimize bleeding risk is to give clopidogrel for as short a period as possible, for example, up to 1 month after elective bare metal stent implantation, and for only 1 year after myocardial infarction.

In addition, the aspirin-prasugrel combination may increase the risk of bleeding even further over clopidogrel/aspirin, Dr. Verheugt said in an interview. This was supported by the findings of the TRITON-TIMI 38 trial, reported at the AHA meeting on November 4. That trial compared clopidogrel directly with prasugrel and found that while prasugrel appeared more effective, major bleeding occurred in 2.4% of patients receiving prasugrel versus 1.8% of patients receiving clopidogrel.

"The aspirin/dipyridamole combination may be safer, but this has not been well tested in cardiology," Dr. Verheugt added.

*Clopidogrel for Reduction of Events During Observation (CREDO); Management of Atherothrombosis With Clopidogrel in High-Risk Patients With Recent Clopidogrel in Unstable angina to prevent Recurrent Events (CURE); Transient Ischaemic Attack or Ischaemic Stroke (MATCH); Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA)
** Stroke Prevention in Atrial Fibrillation (SPAF); Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF)


[Presentation title: Incidence of Severe Bleeding with Long-Term Clopidogrel-Aspirin combination: comparison with Chronic Warfarin Therapy. Abstract 2040]

E-Mail this DGDispatch to a colleague

To print, use this version