Rivaroxaban superior to enoxaparin for VTE prevention after nonmajor orthopedic surgery
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Treatment with rivaroxaban was more effective than enoxaparin for preventing venous thromboembolism during immobilization after lower-limb nonmajor orthopedic surgery, according to results of the PRONOMOS trial.
Among 3,604 patients randomly assigned to oral rivaroxaban (Xarelto, Janssen/Bayer) or subcutaneous enoxaparin, major VTE occurred in 0.2% of the rivaroxaban group compared with 1.1% of the enoxaparin group (RR = 0.25; 95% CI, 0.09-0.75; P < .001 for noninferiority; P = .01 for superiority), according to data presented at the virtual American College of Cardiology Scientific Session.
Incidence of bleeding was not significantly different in the two groups, with major bleeding or nonmajor clinically relevant bleeding reported in 1.1% of patients assigned rivaroxaban vs. 1% assigned enoxaparin and major bleeding in 0.6% vs. 0.7%, respectively, according to the results.
In an additional post hoc analysis comparing the composite of VTE or major bleeding, incidence of the net clinical benefit outcome was 52% lower with rivaroxaban (0.8% vs. 1.8; RR = 0.48; 95% CI, 0.26-0.9), according to the results.
“The net clinical benefit is quite in favor of rivaroxaban. There was no difference according to bleeding and very significant difference in reducing VTE with rivaroxaban,” Nadia Rosencher, MD, senior consultant and anesthesiologist at Paris University, said during the virtual presentation. “In this younger population with moderate risk of VTE after orthopedic surgery, which would require immobilization for at least 2 weeks, rivaroxaban should replace low-molecular-weight enoxaparin, in this case.”
The double-blind, randomized, controlled PRONOMOS trial enrolled adults (median age, 41 years) who underwent lower-limb nonmajor orthopedic surgery and were to receive thromboprophylaxis for at least 2 weeks.
“We must prevent VTEs in these patients because some can lead to pulmonary embolism, which can be fatal,” Rosencher said in a press release. “This study represents a major step forward in our treatment of patients after many orthopedic procedures because it proves that we can more effectively prevent thrombosis with a once-daily oral medication vs. a daily injection with the same safety.”
The rivaroxaban group received 10 mg plus a subcutaneous injection of placebo. The enoxaparin group received subcutaneous enoxaparin (40 mg in 0.4 mL of diluent) plus oral placebo. Mean duration of drug administration was 28 days. The most common surgeries in this population were ligament repair of the knee (37%), ankle fracture (15%) and complicated knee arthroscopy (9%).
The study was conducted between December 2015 and April 2018 at 200 sites in 10 countries. The PRONOMOS steering committee and sponsors stopped enrollment in April 2018 due to slow recruitment of the intended 4,400 patients, which led to the trial drugs reaching expiration dates and then subsequent high replacement costs. Median follow-up was 59 days in both groups. Median follow-up after treatment ended was 33 days in both groups.
During a discussion of the PRONOMOS results, Gregory Piazza, MD, MS, cardiovascular medicine specialist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, commented on the need for prophylaxis research in this population.
“This is a group of patients that, clinically, we recognize to have a high risk of venous thromboembolism but have never received the attention that total hip and total knee replacement have, at least in the prophylaxis literature,” Piazza said. “This was a very important study and it will be one of the most important steps in breaking up some of the heterogeneity in how we treat patients who are undergoing non-total hip and non-total knee surgery. Right now, there is a wide spread on how these patients are treated. Some receive no prophylaxis based on some of the guideline recommendations. Others receive aspirin, warfarin, some receive [direct oral anticoagulants], some receive injectables. It’s the Wild West when it comes to prophylaxis for these patients, and there will be more clarity after this study.” – by Scott Buzby
References:
Rosencher N, et al. Late-Breaking Clinical Trials III. Presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting).
Samama CM, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1913808.
Disclosures: Rosencher reports she received research support from Bayer, is a consultant for Bayer, Bristol-Myers Squibb, Pfizer and Sanofi, received honoraria from Pfizer, Sandoz, Sanofi and Vifor, and is on scientific advisory boards for Bayer, Pfizer and Sandoz. Piazza reports no relevant financial disclosures.