Use of rivaroxaban was superior to placebo for the extended prevention of venous thromboembolism (VTE) in patients after they underwent laparoscopic surgery for colorectal cancer, according to results from the PROLAPS-II study.
“Our study shows that oral rivaroxaban could be a valid alternative to subcutaneous low molecular weight heparin [LMWH] for extended prophylaxis of [VTE] after laparoscopic surgery for colorectal cancer,” said lead author Cecilia Becattini, MD, PhD, of the University of Perugia in Italy.
The incidence of VTE after cancer surgery is higher than that seen in non-cancer surgery. Although in-hospital heparin prophylaxis has been shown to reduce deep vein thrombosis (DVT) and fatal pulmonary embolism (PE), there are no direct comparisons between LMWH and oral rivaroxaban, according to Dr. Becattini.
In the double-blind, investigator-initiated PROLAPS-II study, Dr. Becattini and colleagues compared rivaroxaban with placebo in the extended post-discharge prophylaxis. The study enrolled 582 consecutive patients who had laparoscopic surgery for colorectal cancer and randomly assigned them to 10 mg once daily rivaroxaban or placebo to be started at 7±2 days after surgery and given for the following three weeks. Pre-randomization prophylaxis with LMWH was started 12 to 24 hours after surgery and given until randomization.
The primary outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, or VTE-related death at 28±2 days after surgery. The primary safety outcome was major bleeding.
The median time from surgery to randomization was 6.9 days in both study groups. Mean duration from randomization to primary outcome assessment was 24 days for rivaroxaban and 23 days for placebo.
“In this setting, rivaroxaban reduced the incidence of VTE in comparison to placebo, without safety concerns,” Dr. Becattini said.
The primary outcome event occurred in 11 of 282 patients in the placebo group compared with three of 287 patients in the rivaroxaban group (3.9% vs. 1.0%; odds ratio [OR] = 0.26; 95% CI 0.07-0.94; log rank p=0.032). None of the events were PE.
In a per protocol analysis that excluded 26 patients with major violations, a primary outcome event occurred in 1.2% of patients assigned rivaroxaban and 4.1% of patients assigned placebo. Some of the major violations included declined consent, adverse events, physician decisions, or required re-intervention.
“The advantage of extended prophylaxis with rivaroxaban in comparison to that with LMWH is mainly related to improved feasibility,” Dr. Becattini said. “The efficacy and safety of rivaroxaban in comparison to LMWH in this indication is still unexplored.”
No major bleeding occurred in patients assigned to placebo, and 0.7% of patients assigned to rivaroxaban experienced major bleeding. In the two patients with major bleeding, the bleeding occurred at the surgical site. No fatal bleeding occurred.
Study limitations included slower than anticipated recruitment, which led the study drug to expire when about 90% of patients had been randomized. Additionally, pre-randomization antithrombotic prophylaxis and mechanical prophylaxis were not standardized but were left to investigators’ discretion. Time from randomization to primary outcome assessment was longer than expected, partially due to limited accessibility to study centers during the COVID-19 pandemic.
In the discussion of the results, the researchers acknowledged that the rate of VTE was lower than anticipated. Data that led to the recommendation of long-term antithrombotic prophylaxis are mostly from before the era of laparoscopic surgery, Dr. Becattini said.
“Differences in study design, together with the 20 years of advancement in the surgical theatre could explain the low incidence of primary outcome observed in our study,” Dr. Becattini said. “Further studies are required to confirm our incidence rates.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Becattini C, Pace U, Pirozzi F, et al. Rivaroxaban versus placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer [published online ahead of print, 2022 May 17]. Blood. doi: 10.1182/blood.2022015796.