Dabigatran a Danger for Mechanical Valves?

Prosthetic heart valve patients gained no benefit from dabigatran to prevent blood clots

(RxWiki News) Some patients with weak heart valves opt to get an artificial valve to improve heart function. These valves require lifelong anticlotting medication, but some medications may be more effective than others.

Dabigatran (brand name Pradaxa) is an anticoagulant, an agent that reduces blood clotting in arteries, veins or the heart. The medication has been shown to be effective in patients with atrial fibrillation (an irregular and often rapid heart beat).

Scientists speculated that dabigatran might also prevent clotting (thrombosis) and related complications in patients who had surgery to receive a mechanical heart valve. Patients with heart disease that weakens the valves may get mechanical valves to replace their own if their heart valves are not working as they should.

A new study found, however, that patients with mechanical heart valves who took the anticlotting medication dabigatran, compared with those who took a commonly used anticlotting therapy, were more likely to have complications due to bleeding and blood clots. 

"Ask a pharmacist about the side effects of dabigatran."

Frans Van de Werf, MD, professor of cardiology at University of Leuven, Belgium, and colleagues compared the effectiveness of dabigatran versus warfarin (brand names Coumadin and Jantoven), an anticoagulant that is commonly used for patients with mechanical heart valves.

Dr. Van de Werf and his team noted that warfarin provides excellent protection against blood clotting in these patients but requires “...restrictions on food, alcohol, and drugs and lifelong coagulation monitoring.”

For this study, 162 patients received dabigatran and 81 received warfarin. Dosing was based on each patient's kidney function.

In the dabigatran group, there were nine strokes that were ischemic (due to a clot) or unspecified. Those in the warfarin group had zero strokes.

More dabigatran patients also had major bleeding — seven dabigatran patients compared to two of the warfarin patients.

The trial was discontinued early because of clotting and bleeding events among those in the dabigatran group. More than a quarter of the dabigatran patients had a bleeding episode of any degree, compared with 12 percent of those taking warfarin.

“The use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic [blocking of a blood vessel] and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk,” the authors wrote.

In a related commentary, Elaine Hylek, MD, professor of medicine at Boston University School of Medicine, speculated that the poor results for dabigatran may partially be explained by the fact that about 80 percent of the patients had recently undergone surgery.

“The early postoperative period may have been less than optimal for testing a new fixed-dose drug regimen because of the enhanced thrombogenicity [tendency to produce a clot] inherent in such patients,” wrote Dr. Hylek.

While the US Food and Drug Administration (FDA) and the European Medicines Agency have recommended against the use of dabigatran in patients with mechanical heart valves and the results of this study were “disappointing,” Dr. Hylek believes that it is “premature” to abandon research in the use of such medications in patients with mechanical heart valves.

This study and related commentary were published at the beginning of September in The New England Journal of Medicine. The study was supported by Boehringer Ingelheim, the manufacturer of Pradaxa.

Review Date: 
September 5, 2013