In a recent trial, switching to low-dose aspirin was just as effective at preventing blood clots after joint replacement surgery as continuing the anti-clotting drug rivaroxaban. Six per 1,000 people taking aspirin experienced a blood clot, compared with seven per 1,000 taking rivaroxaban. Three to five per 1,000 patients experienced major bleeding with either drug.
Rivaroxaban or similar drugs are usually prescribed for two or five weeks after knee or hip surgery, respectively, to reduce the risk of blood clots in the legs or lungs.
This trial included over 3,000 adults who received rivaroxaban for the first five days after surgery and then either continued with the drug as is current practice or switched to aspirin.
The findings suggest that aspirin is an equally safe and effective alternative after initial rivaroxaban prophylaxis, though the chance of a clot or bleeding was small for both strategies. Aspirin is a cheap drug, and that could reduce costs of prevention if patients are switched to it after five days, by when most are discharged. Aspirin is not licensed for this use, but NICE 2018 guidelines recommend it as an option.
It’s unclear if these results would apply to groups with a higher risk of thrombosis.
Why was this study needed?
The UK National Joint Registry reports that there were 101,651 hip replacement procedures and 108,713 knee replacements recorded in 2016, an increase of nearly 4% on 2015. Blood clots in the legs (deep vein thrombosis [DVT]) or the lungs (pulmonary embolism) are well-recognised complications in the postoperative period that require extended preventive measures.
Anti-clotting (anticoagulant) drugs like rivaroxaban and apixaban are widely used as they are safe, effective and convenient, being taken by mouth. Several studies have suggested that aspirin may be an alternative, at least after an initial period of anticoagulation, but there have been no trials comparing it directly against anticoagulants.
The Canadian EPCAT II trial (Extended Venous Thromboembolism Prophylaxis Comparing Rivaroxaban to Aspirin Following Total Hip and Knee Arthroplasty II) meets that need.
What did this study do?
The randomised trial included 3,424 adults after total hip or knee replacement across 15 centres in Canada. All patients received rivaroxaban (10mg daily) immediately following surgery for five days. From day six they were randomised to continue rivaroxaban or switch to aspirin (81mg daily) for an additional nine days following knee surgery or 30 days following hip surgery.
The drugs were given in identical capsules, so neither patients nor researchers knew what they were taking. Randomisation was balanced according to whether patients were already taking low-dose aspirin. In this case, patients continued with their standard aspirin alongside the assigned drug. The trial included sufficient patients to be able to rule out what experts thought was a clinically important difference (1%) in the rate of DVT or pulmonary embolism between groups.
What did it find?
- Aspirin was just as effective as rivaroxaban at preventing symptomatic DVT or pulmonary embolism. These events occurred in 0.64% (11/1,707) of patients in the aspirin group and 0.70% (12/1,717) in the rivaroxaban group (difference 0.06%, 95% confidence interval [CI] -0.55% to +0.66%).
- There was also no difference in the rate of major bleeding, which affected 0.47% (8/1,707) of the aspirin group and 0.29% (5/1,717) of the rivaroxaban group (difference 0.18%, 95% CI -0.65% to +0.29%). Neither was there a difference when including non-major bleeding (1.29% with aspirin vs 0.99% with rivaroxaban). All events involved bleeding at the surgical site.
- There was a single death from pulmonary embolism. This occurred in a patient assigned to aspirin after knee replacement. It happened 17 days after finishing aspirin treatment.
- Results were similar across the different operations, and when looking at those already taking long-term aspirin or not.
What does current guidance say on this issue?
Recent NICE guidelines (2018) on reducing risk of hospital-acquired venous thromboembolism recommend aspirin as an option, though not the switching strategy from rivaroxaban.
Recommended options after hip replacement are:
- Low molecular weight heparin (LMWH) for 10 days followed by aspirin (75 to 150mg) for 28 days; or
- LMWH for 28 days plus compression stockings until discharge; or
- Rivaroxaban (10mg daily) for five weeks (in line with the NICE 2009 technology appraisal).
Recommended options after knee replacement are:
- Aspirin (75 to 150mg) for 14 days; or
- LMWH for 14 days plus compression stockings until discharge; or
- Rivaroxaban (10mg daily) for two weeks.
What are the implications?
Enough patients were included to demonstrate the equivalence of low-dose aspirin with rivaroxaban after knee or hip replacement. Results generally support new NICE recommendations to consider aspirin as an option and as aspirin is a low-cost drug it could save resources on prevention, though treatment of clots and complications if they occurred, would remain the same.
The trial didn’t compare treatments started immediately post-operatively, and it is possible that much of the benefit comes from the first five days of rivaroxaban. The authors note that most bleeding events occurred in the early postoperative period too.
Questions remain about the optimal time to start aspirin and how long to continue it. It is not clear whether patient characteristics should guide treatment choice.
Citation and Funding
Anderson DR, Dunbar M, Murnaghan J, et al. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018;378:699-707.
This project was funded by the Canadian Institutes of Health Research.
NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. NG89. London: National Institute for Health and Care Excellence; 2018.
NICE. Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. TA170. London: National Institute for Health and Care Excellence; 2009.
NJR. 14th annual report 2017. Hemel Hempstead: National Joint Registry; 2017.
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