Among patients who underwent total hip or total knee arthroplasty, aspirin did not differ significantly from rivaroxaban (Xarelto, Janssen Pharmaceutica) for prevention of proximal deep-vein thrombosis or pulmonary embolism, after both groups received a 5-day course of rivaroxaban immediately after surgery, a large trial found.
"In our trial, we found that the inexpensive, widely available generic agent aspirin was not significantly different from the more expensive, direct oral anticoagulant rivaroxaban for the prevention of symptomatic, clinically important venous thromboembolism after total hip or total knee arthroplasty among patients who had received an initial 5-day postoperative course of rivaroxaban," write David R. Anderson, from the Department of Medicine, and colleagues. The researchers report their findings in an article published online in the New England Journal of Medicine.
The multicenter, double-blind, randomized controlled trial, called Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty II (EPCAT II), enrolled 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty). The mean age of participants was 62.8 years, and 47.8% were male.
Study participants were followed up for 90 days for the primary effectiveness outcome, symptomatic venous thromboembolism, and the primary safety outcome, bleeding complications, including major or clinically relevant nonmajor bleeding.
During the 90-day follow-up period, 11 (0.64%) of 1707 patients in the aspirin group and 12 (0.70%) of 1717 patients in the rivaroxaban group developed symptomatic proximal deep-vein thrombosis or pulmonary embolism (difference, 0.06 percentage points; 95% confidence interval [CI], −0.55 to 0.66).
Aspirin was noninferior (P < .001) but not superior (P = .84) to rivaroxaban for preventing postoperative proximal deep-vein thrombosis or pulmonary embolism, which was the primary endpoint.
One patient in the aspirin group who underwent total knee arthroplasty died from pulmonary embolism 31 days after randomization and 17 days after completing aspirin prophylaxis. No other patients died during the trial.
"There were no between-group differences in effectiveness in the subgroup of patients who were receiving long-term aspirin therapy, which suggests that there was no benefit of adding 81 mg of aspirin to either aspirin or rivaroxaban prophylaxis," the authors explain.
Rates of thromboembolism, major bleeding, and clinically relevant nonmajor bleeding were not significantly different among the 855 patients who were and the 2569 patients who were not receiving long-term aspirin therapy.
"[T]here were suggestions of more major and clinically relevant nonmajor bleeding among patients in the long-term aspirin subgroup, particularly among those who had been assigned to the aspirin group and hence were receiving a second daily dose of aspirin prophylaxis," the researchers write.
Eight patients (0.47%) in the aspirin group and five patients (0.29%) in the rivaroxaban group experienced major bleeding events (difference, 0.18 percentage points; 95% CI, −0.65 to 0.29; P = .42). Twenty-two patients (1.29%) in the aspirin group and 17 patients (0.99%) in the rivaroxaban group experienced a combination of major bleeding and clinically relevant nonmajor bleeding (difference, 0.30 percentage points; 95% CI, −1.07 to 0.47; P = .43).
All bleeding events were overt hemorrhage that occurred at the surgical site, and most occurred within 10 days after randomization.
Treatment Strategies Should Evolve as Practice Patterns Change
Having randomized controlled trials, which are very difficult to do, and expensive and time-consuming, is critically important in helping us understand and evaluate important clinical questions like this.
As practice evolves, it's important to reevaluate strategy, so what may have been appropriate for VTE prophylaxis 10 or 15 years ago may not be appropriate today because surgical techniques have changed, rehabilitation protocols have changed; for instance, patients are getting up and mobilizing on the day of surgery, and being discharged home on the day of surgery in many cases.
"This significantly reduces their risk for venous thromboembolism complications, whereas in an era when patients were staying in the hospital and staying in bed for many days, that increased their risk for VTE complications," Bozic continued.
"It's important to reevaluate treatment strategies as practice patterns change," Bozic concluded.