Dabigatran Etexilate and Knee or Hip Replacement Surgery

Los Angeles—An open-label, prospective, observational study found that dabigatran etexilate was effective and well tolerated in patients undergoing total knee or hip replacement surgery.

The incidence of symptomatic venous thromboemolic events (VTEs) and all-cause mortality, the primary efficacy end point, was lower in patients who underwent total hip replacement surgery. The incidence of major bleeding events, the primary safety end point, was comparable in the 2 groups.

Results were presented at the AHA meeting during a poster session. The poster was titled Safety and Efficacy of Once-Daily 220-mg Dabigatran Etexilate in a Real-World Non-Interventional Study of more than 5000 Patients after Total Knee or Hip Replacement.

In October 2010, the FDA approved dabigatran etexilate to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The drug, a direct thrombin inhibitor, has also been approved in >80 countries (not in the United States) for the primary prevention of VTEs after elective total knee or hip replacement surgery. The authors noted that phase 3 trials found 220 mg of dabigatran etexilate taken daily was as effective as daily 40-mg doses of enoxaparin to prevent VTEs following total knee or hip replacement surgery.

In this study, 5292 patients between 18 and 75 years of age were treated with 220 mg of dabigatran etexilate daily between March 2009 and July 2011. Exclusion criteria included concomitant amiodarone or quinidine treatment, an indication for quinidine or chronic anticoagulant therapy, renal or hepatic impairment, active clinically significant bleeding, or spontaneous or pharmacological impairment of haemostasis.

All patients had 3 visits: (1) at baseline (≤7 days before surgery); (2) when discharged from the hospital or 24 to 48 hours after ending treatment (whichever came first); and (3) at follow-up if they were discharged before finishing treatment.

Of the patients, 2734 underwent hip replacement surgery and 2558 underwent knee replacement surgery. The mean age was 62.6 years, 42.2% of patients were male, and 99.0% were white.

The overall incidence of major bleeding events was 0.72% (95% confidence interval [CI], 0.51%-0.98%), and the incidence was similar in the hip replacement (0.69%; 95% CI, 0.42%-1.08%) and knee replacement (0.74%; 95% CI, 0.45%-1.16%) groups.

The authors defined major bleeding events as clinically overt bleeding; fatal, retroperitoneal, intracranial, intraocular, or intraspinal bleeding; or bleeding warranting treatment cessation or leading to reoperation.

In patients with at least 1 risk factor for bleeding, the incidence of major bleeding events was 0.76%, which was comparable to the 0.64% incidence among patients with no risk factors. The risk factors were active smoking, coronary artery disease, chronic heart failure, history of VTE, concomitant acetylsalicyclic acid, and chronic use of non-steroidal anti-inflammatory drugs.

Of the patients, 18.7% had an adverse event, 2.6% had a serious adverse event, and 4.9% had an adverse event that led to discontinuation of dabigatran etexilate.

The incidence of symptomatic VTEs and all-cause mortality was 1.04% (95% CI, 0.78%-1.35%), including 0.55% (95% CI, 0.31%-0.90%) in patients undergoing hip replacement and 1.56% (95% CI, 1.12%-2.12%) in patients undergoing knee replacement.

Patients with a history of VTE had a higher incidence than those without a history of VTE (odds ratio, 5.59; 95% CI, 2.53-11.08). The authors noted none of the other risk factors had much of an impact on the incidence of symptomatic VTEs and all-cause mortality.

This poster was sponsored by Boehringer Ingelheim.