Switch to Rivaroxaban Led to Higher Complication Rate

By: Terry Stanton

Terry Stanton

The rate of wound complications in British patients undergoing total knee or total hip replacement rose significantly when the anticoagulant rivaroxaban was used in place of tinzaparin for thromboprophylaxis. When physicians noted this and returned to using tinzaparin, the return to surgery rate decreased, according to the Scientific Poster, “Effect of Rivaroxaban on Return to Theatre Rates Following Total Hip and Knee Replacement.”

In the United States, rivaroxaban was approved as prophylaxis for deep vein thrombosis after hip and knee arthroplasty in June 2011. Tinzaparin is also approved in the United States for a variety of indications, including prophylaxis of deep vein thrombosis and pulmonary embolism.

Retrospective cohort analysis
This retrospective cohort analysis included 1,558 consecutive patients undergoing joint replacement within the same hospital over a 19-month period (2009–2011). In the first group of 489 patients, who received tinzaparin, the rate of wound complications requiring a return to surgery within 30 days was 1.8 percent (9 patients).

The next 559 patients were given rivaroxaban and had a return-to-surgery rate of 3.94 percent (22 patients), a significant increase (P = 0.046). After 7 months of rivaroxaban use in what would become the study’s second group of patients, concerns arose over its safety in regard to large, fresh wounds. The surgery department elected to resume use of tinzaparin, which had been the previous standard therapy.

The final 510 patients received tinzaparin, and had a wound complication rate requiring a return to surgery of 1.6 percent (8 patients). The decrease between the rates for the rivaroxaban group and this tinzaparin group was also statistically significant (P = 0.02). When the first and third groups were combined and compared with the rivaroxaban group, the significance increased.

Across the study groups, all aspects of the perioperative care were standardized, including antibiotic prophylaxis, compression stockings, lack of wound drains, and encouragement of early mobilizing. Indications for return to surgery did not change during the period and were based on clinical suspicion of wound infection or hematoma and increased inflammatory markers.

The study was conducted by Cyrus D. Jensen, MRCS; Rebecca Morrell, MBBS; Andrew Steval, MBBS; Paul F. Partington, MD; FRCS; Mike R. Reed, MD, FRCS; and Scott D. Mullet, MD, FRCS.

Recently approved prophylaxis
Rivaroxaban is the one of the world’s first orally active direct Factor Xa inhibitors. In both intrinsic and extrinsic clotting cascades, factor Xa helps to convert prothrombin into thrombin, and it is this mechanism that is inhibited. Rivaroxaban is well absorbed by the gut and so can be delivered orally, in contrast with the subcutaneously administered heparins, thus making it more acceptable to the general public and improving compliance rates.

The switch to rivaroxaban was made after the drug was approved for chemical thromboprophylaxis in the European Union. The authors note, however, that this recommendation was based solely on four sponsored studies.

A report issued by the National Institute of Health and Clinical Excellence (NICE) comparing rivaroxaban and enoxaparin had focused on major bleeding as the primary safety outcome, paying less attention to wound complications such as prolonged bleeding/oozing and infection.

Commenting on their findings, the authors note that “releases of new NICE guidelines have a huge impact on UK practice, not always with a predictable effect.” They write.”

The study has several limitations, including its observational nature, varied group size, and participation by multiple surgeons. The authors sought to mitigate this by looking at rates rather than absolute numbers of return to surgery. As a result, they say, further independent trials are needed to assess new anticoagulants.

The authors reported no conflicts.