Warfarin and Pradaxa Bleeding Rates Similar After Surgery: Study

The findings of a new study suggest that the rates for bleeding and thromboembolic complications are similar between users of Pradaxa and warfarin, when patients on the anticoagulants need to undergo surgery. 

In a report published on-line this week by the American Heart Association’s Circulation journal, researchers gleaning more data from the controversial RE-LY clinical trials, which were used to obtain FDA approval for Pradaxa in 2010.

Scientists and doctors from Canada found that Pradaxa and warfarin had comparable rates of peri-procedural bleeding. However, Pradaxa was associated with a shorter interruption of drug treatment, meaning that patients were able to stop using it closer to surgery than warfarin, to let the blood-thinning effects wear off.

Patients suffering from atrial fibrillation who needed surgery were observed seven days before the procedure until 30 days after, for bleeding rates and other complications. Researchers found virtually the same rate of stroke, cardiovascular death, heart attack and pulmonary embolism among those who took Pradaxa and those who took warfarin, often known by its brand name, Coumadin.

Bleeding events were also very similar between the two drugs, whether it was planned surgery or an emergency. However, patients were able to stop taking Pradaxa much closer to the date of a planned surgery than warfarin, because the anticoagulant effects of the drug wore off faster. When patients took warfarin within 48 hours of surgery, they faced two to three times the chance of bleeding problems.

Pradaxa (dabigitran) was introduced as the first of a new class of anticoagulants developed as an alternative to warfarin for the prevention of stroke among patients with atrial fibrillation. The medication has been promoted as superior because it is easier to use and requires less monitoring. However, serious concerns have emerged about the risk of severe bleeding problems with Pradaxa, as it has been associated with thousands of reports involving uncontrolled hemorrhaging and hundreds of patient deaths.

While bleeding problems that develop with use of warfarin can be reversed through a dose of Vitamin K, which can be given to patients to stop the drug’s anticoagulation effects, no such reversal agent is available for Pradaxa users.  Therefore, doctors are often left unable to stop bleeding, potentially resulting in serious injury or death.

According to a report released last month by the Institute for Safe Medication Practices (ISMP), there were more adverse event reports submitted to the FDA last year involving problems with Pradaxa than any other medication. During the first full year Pradaxa was available, the FDA received at least 3,781 reports involving serious injuries associated with Pradaxa, including 2,367 reports of hemorrhage and 542 patient deaths.  By comparison, warfarin was linked to 1,106 adverse event reports and 72 patients deaths.

The RE-LY study, which was the basis for this latest report, has come under fire from critics, who have suggested that Pradaxa never should have been approved based on the trial results.

In a letter published last year in the journal Therapeutics Initiative (PDF), researchers from the University of British Columbia described the clinical trials as fundamentally flawed, allowing bias and errors to creep into the results. The trial used a double-blind comparison between two doses of Pradaxa, but a non-blinded comparison between Pradaxa and warfarin, raising questions about the integrity of the data.

Although some have suggested that a Pradaxa recall should be issued given the bleeding problems associated with the medication, such regulatory action does not appear likely. While the FDA is continuing to review recent adverse event reports, European regulators indicated last month that the risks appear to be outweighed by the benefits provided by the medication. However, the European Medicines Agency (EMA) recommended that stronger Pradaxa warnings and information be provided about the best use of the medication, including more specific guidance on when Pradaxa should not be used and how to best manage bleeding problems that do occur.

Boehringer Ingelheim, the manufacturers of the medication, currently face a growing number of Pradaxa lawsuits brought on behalf of individuals who have experienced bleeeding problems. The complaints allege that the drug maker failed to adequately warn about the risk of bleeding or the lack of a reversal agent.