Rivaroxaban superior to enoxaparin in preventing VTE in non-major orthopaedic surgery

Oral rivaroxaban has shown to be superior to subcutaneous enoxaparin in preventing venous thromboembolism (VTE) in patients undergoing non-major orthopaedic surgery with a period of immobilisation [1,2]. No significant difference was observed in major bleeding with rivaroxaban versus enoxaparin.

Prof. Nadia Rosencher (Paris Center University Hospital, France) and colleagues in the PRONOMOS trial aimed to compare the effect of rivaroxaban with that of enoxaparin in preventing major VTE during immobilisation after lower-limb non-major orthopaedic surgery [1]. The trial enrolled 3,604 adult patients who underwent non-major orthopaedic surgery of the lower limbs and who required thromboprophylaxis for >2 weeks (investigator’s assessment). The primary efficacy endpoint of the study was major VTE, a composite of symptomatic distal or proximal deep-vein thromboembolism (DVT), pulmonary embolism, or VTE-related death during the treatment period, or asymptomatic proximal DVT at the end of treatment. Safety outcomes were major and clinically relevant non-major bleeding. Participants were enrolled between December 2015 and April 2018 at 200 sites in 10 countries. As recruitment of patients was slower than expected, enrolment was terminated early due to drug supply issues. Participants had a mean age of 41 years and median body mass index of 26.3 kg/m². Many types of surgery were included in the study (median duration 60 minutes), with the most common being ligament repair of the knee, ankle fracture, and knee arthroscopy. A prophylactic dose of low-molecular-weight heparin was given prior to surgery to 13.8% of patients. The patients were randomised to receive 10 mg oral rivaroxaban and a placebo injection (n=1,809) or enoxaparin (40 mg in 0.4 mL of diluent) plus a placebo oral tablet (n=1,795).

The results showed that 0.2% of patients on rivaroxaban experienced VTE (n=4) versus 1.1% of patients receiving enoxaparin (n=18; risk ratio [RR] 0.25; 95% CI 0.09-0.75; P<0.001 for non-inferiority, P=0.01 for superiority). Symptomatic VTE was seen in 0.2% versus 0.6% of patients, respectively (RR 0.28; 95% CI 0.08-1.00). Asymptomatic proximal DVT was seen in 0.1% of the rivaroxaban group versus 0.4% of the enoxaparin group. Major and non-major clinically relevant bleeding occurred in 1.1% of rivaroxaban patients and 1.0% of enoxaparin patients (RR 1.04; 95% CI 0.55-2.00). Although this study was prematurely stopped because of low accrual, and is therefore limited in impact, the net clinical benefit of VTE + major bleeding was 0.8% for rivaroxaban and 1.8% for enoxaparin (RR 0.48; 95% CI 0.26-0.90). These findings suggest that rivaroxaban could replace enoxaparin to prevent VTE during postoperative reduced mobility after non-major orthopaedic surgery in at-risk patients.

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   1. Samama CM, et al. Abstract 406-11. ACC/WCC 28-30 March 2020.
   2. Samama CM, et al. N Engl J Med. 2020. DOI:10.1056/NEJMoa1913808.

Posted on 7 September, 20209 December, 2020