Extended venous thromboembolism prophylaxis comparing rivaroxaban to aspirin following total hip and knee arthroplasty

Abstract

Deep vein thrombosis and pulmonary embolism are common complications post-total hip (THA) and total knee arthroplasty (TKA). Prophylaxis with direct oral anticoagulants, such as rivaroxaban extended beyond hospital discharged is commonly prescribed for the prevention of these complications. We reasoned aspirin (ASA) potentially would be an attractive alternative agent for extended prophylaxis because of its low cost, convenience and few side effects. Objective was to determine if aspirin was as effective and safe as rivaroxaban for extended prophylaxis in patients already having received five days of rivaroxaban prophylaxis post-total hip or total knee arthroplasty. This was a 15-centers Canadian, double-blind, randomized controlled trial following THA and TKA. All patients received rivaroxaban 10 mg orally once daily until postoperative day 5 and then were randomized to continue rivaroxaban 10 mg daily or be switched to aspirin 81 mg daily. Prophylaxis was continued for an additional 9 days following TKA or 30 days following THA. All patients were followed for 90 days for the development of symptomatic proximal deep vein thrombosis and pulmonary embolism confirmed by objective testing or clinically important bleeding complications. The target sample size was 3426 patients based upon a non-inferiority design and the primary analysis was intention-to-treat. A total of 3427 patients were randomized and 3424 patients were included in the intention to treat analysis (1804 THA and 1620 TKA). The mean age of patients was 63 and 48% of patients were male. Eleven (0.64%) patients randomized to rivaroxaban experienced deep vein thrombosis or pulmonary embolism compared with 12 (0.70%) of patients randomized to aspirin (P less than 0.0001 for non-inferiority and 0.84 for superiority). Seven (0.99%) of patients receiving rivaroxaban and 22 (1.3%) of patients receiving aspirin experienced clinically important bleeding complications (absolute difference 0.30%, P = 0.4). Predefined efficacy analyses also showed no significant differences in rates of complications. Venous thromboembolism is a common complication after THA and TKA. Administration of antithrombotic prophylaxis has been proved to effective. On the other hand, extending prophylaxis with novel agents like rivaroxaban increases the cost of care of patients and is associated with increased bleeding events. Simplified, inexpensive alternative therapies as aspirine would be welcome. This study showed that extended prophylaxis with aspirin was at least as effective and safe as rivaroxaban. Given its low cost, aspirin is an attractive alternative for this indication.