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Among younger patients undergoing total hip or knee replacement, whether they received aspirin versus direct oral anticoagulants (DOACs) did not seem to affect their risk of venous thromboembolism (VTE) following surgery, a large retrospective study indicated.

But bleeding rates were higher with DOACs, reported Brian Hollenbeck, MD, of New England Baptist Hospital in Boston, and colleagues in .

Among propensity-matched patients with records in the MarketScan database of private insurance claims, the odds of experiencing VTE were a nonsignificant 14% higher among those receiving DOACs versus aspirin (OR 1.14, 95% CI 0.82-1.59). The incidence of postoperative bleeding, however, was definitely greater with DOACs (OR 1.36, 95% CI 1.13-1.62).

VTE risk was almost entirely predicted by standard patient-related factors, the group found:

• Previous VTE (OR 5.94, 95% CI 4.29-8.24)

• Hereditary hypercoagulability (OR 2.64, 95% CI 1.32-5.28)

• Male sex (OR 1.34, 95% CI 1.08-1.67)

• Knee versus hip replacement (OR 1.65, 95% CI 1.29-2.10)

"These results suggest a need for patient-centric thromboprophylaxis strategies tailored to individual risk of thrombosis and bleeding," Hollenbeck's group concluded.

Over the past 10 years, DOACs including apixaban (Eliquis) and rivaroxaban (Xarelto) have become popular for preventing VTE after arthroplasty, alongside conventional drugs such as warfarin. Aspirin, too, has been gaining. Real-world comparisons among them for VTE and bleeding risk, however, have been lacking, the researchers said.

Consequently, they turned to MarketScan data, which covers some 245 million individuals with private insurance, as well as those with employer-paid Medicare supplemental insurance. The group analyzed 3 years of data spanning 2017 through 2019, looking for people undergoing hip or knee replacements and who had continuous insurance coverage for 3 months prior to and following their procedures. For individuals who had both left and right joints replaced, only the first procedure was included. Those who received anticoagulants prior to a 2-week period before their procedures were excluded, as were those who didn't get any postoperative anticoagulants or who were given more than one such drug.

About 132,000 people in the database had total knee or hip procedures during the study period, but for more than 95,000, their records didn't indicate a thromboprophylaxis prescription. With other exclusions, the final analysis covered 29,264 patients. Some 63% had knee replacements; 42% were men, and 82% were younger than 65.

The primary outcome was VTE incidence (deep vein thrombosis and/or pulmonary embolism) within 30 days after surgery; 90-day VTE incidence was tracked too. Any type of bleeding event receiving treatment, and hence included in the claims data, within 30 and 90 days was counted.

In this group, 34.5% received aspirin, 19.7% enoxaparin, 11.1% warfarin, 24.2% rivaroxaban, and 10.6% apixaban. Overall, 30-day rates were 1.19% for VTE and 3.43% for bleeding events. At 90 days, rates stood at 1.86% and 5.33%, respectively.

After adjusting for certain risk factors, 30-day VTE rates appeared lowest for aspirin, with odds ratios of 1.21-2.26 for warfarin, rivaroxaban, apixaban, and enoxaparin versus aspirin. For all but apixaban, the differences were statistically significant. Bleeding risk within 30 days was also numerically greater with these agents versus aspirin, with odds ratios of 1.28-1.43.

But in a propensity-matched comparison of aspirin with the two DOACs -- with 7,844 patients in each group -- the differences in VTE risk shrank into insignificance, even as the higher bleeding risk with DOACs became clearer. Findings were similar for 90-day risks for VTE and bleeding. One factor driving these results might have been that aspirin was taken for longer than were DOACs: median durations were 31 days for aspirin versus 18 days for DOACs.

In general, Hollenbeck and colleagues said, their results support a recent trend to prefer aspirin for postsurgical VTE prevention on account of comparable efficacy and lower bleeding risk. One randomized trial favored enoxaparin over aspirin, while others indicated rough equivalence between aspirin and competing therapies. A trial is now ongoing, the researchers noted; results are expected in 2025.

The new study did come with substantial limitations. Although these were real-world data, they covered only a tiny fraction of the estimated 1.5 million knee and hip replacement performed annually in the U.S. Most patients were younger than 65, since these were individuals with private employer-paid insurance. And, of course, the study relied on administrative data that don't include all potentially relevant information and may contain errors.

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