Rivaroxaban ranks top for VTE prevention among immobilized patients following trauma

France: A research article published in PLOS Medicine confirmed the efficacy of anticoagulants in preventing Venous Thromboembolism (VTE) in lower extremity trauma involving immobilization. The study confirmed rivaroxaban as the best efficacious and safe treatment approach. The aspirin has uncertain efficacy and requires further investigation.

The main contributing factor to venous thromboembolism (VTE) is immobilization following lower limb trauma, including deep vein thrombosis (DVT) and Pulmonary embolism (PE). The indication and prophylaxis are a matter of debate regarding how clinically effective thromboprophylaxis is in such cases. Evidence suggests that pharmacological prophylaxis could reduce VTE, but the treatment with the best clinical benefit remains unclear. Horner and colleagues addressed the only network meta-analysis (NMA) on this population group, but it had limitations. England, Germany, and Australia have proposed that the risk of thrombosis assessment is vital before initiating thromboprophylaxis.

Against the above background, a study from Emergency Department, Angers University Hospital, Health Faculty, Angers, France, assessed the efficacy of thromboprophylaxis in preventing VTE in immobilized patients (isolated temporary lower limb) after trauma. The team, led by Douillet et al. with co-researcher Chapell, compared the efficacy and safety of different thromboprophylaxis treatments to determine the best possible strategy.

The strategies used in the study were Low Molecular Weight Heparin, fondaparinux, aspirin, rivaroxaban, and control. These were compared against one another, and the most efficient with the highest level of evidence was concluded in the study.

The lead and co-author, Douillet and Chapelle team, conducted a computer-assisted search on electronic databases, namely Medline, Embase, Google Scholar, the Cochrane Library, and the international clinical trials database. The keywords used were trauma, injury, immobilization, casts, Achilles' tendon rupture, LMWH, fondaparinux, DOAC, and aspirin in combination with a controlled or randomized trial, study, observational, and cohort study. The primary efficacy endpoint was major VTE, and the primary safety endpoint was major bleeding.

The key pointers of the study are:

• 14 RCTs were included with 8,198 patients.

• Outcomes for major VTE were reported in 13 trials.

• The rate of major VTE was 0% to 11.7%, symptomatic VTE in the range of 0% to 2.1%, and PE in the range of 0% to 2.1% without pharmacological thromboprophylaxis in the control group.

• Rivaroxaban was associated with a significant risk reduction of major VTE in adults with an Odds Ratio (OR) of 0.02.

• Fondaparinux had an OR of 0.22.

• Odds Ratio for LMWH was 0.32.

• Aspirin had an OR of 0.13 and was not associated with a significant risk reduction of major VTE.

• In the POT-CAST study, one death was reported and was related to PE.

• Rivaroxaban was more effective than LMWH and was ranked first with a confidence interval between 1 to 2

• Fondaparinux was ranked second, and LMWH ranked third.

• Rivaroxaban had the highest likelihood of efficacy with surface under the cumulative ranking curve (SUCRA) 94.9%.

• Fondaparinux had SUCRA 52.6% and LMWH had SUCRA 37.7%.

• Aspirin was not ranked due to ineffectiveness.

• Considering sensitivity analysis, symptomatic VTE endpoint, the magnitude effect was similar for the major VTE endpoint. The OR was 0.05, 0.19, and 0.41 for rivaroxaban, fondaparinux, and LMWH, respectively.

• Major bleeding data was available for 13 studies and was not reported with rivaroxaban.

• A total of 9 patients had nonmajor clinically relevant bleeding: 3 in the rivaroxaban group (out of 1,078 patients), 5 in the LMWH (among 3353 patients) group, and 1 in the fondaparinux group (among 766 patients).

• Rivaroxaban had an increased net clinical benefit with an OR of 0.02, and was more effective than LMWH and fondaparinux.

• The clinical benefit of fondaparinux was presented with an OR of 0.25, followed by LMWH with OR of 0.34

The study had the strength of data analysis from a large sample size and the PRONOMOS study. The research answered the most important question in thromboprophylaxis.

The final conclusion from researchers was," Rivaroxaban, Fondaparinux, and LMWH are efficacious in preventing VTE in lower extremity trauma with immobilization as compared to placebo. However, rivaroxaban is top-ranked in terms of efficacy and net clinical benefit. Thromboprophylaxis depends on factors like cost-effectiveness and utility, baseline risk, medical experience, risk score, and patient preference."

The researchers acknowledged Prof. Marc Samama for agreeing to use the individual data from the PRONOMOS study. The authors added that PRONOMOS was the first study assessing rivaroxaban's efficacy and safety.

References:

Douillet D, Chapelle C, Ollier E, Mismetti P, Roy P-M, Laporte S (2022) Prevention of venous thromboembolic events in patients with lower leg immobilization after trauma: Systematic review and network meta-analysis with meta epidemiological approach. PLoS Med 19(7): e1004059.