Anderson DR, et al. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. NEJM 2018;378:699-707.
Bottom line: In patients who underwent elective hip or knee replacement with rivaroxaban 10 mg/d up until POD #5, switching to ASA 81 mg/d on POD #6 is no worse than continuing rivaroxaban 10 mg/d for preventing VTE, with similar rates of bleeding.
Patients (n=3427)
- Setting: 15 Canadian university-affiliated hospitals from Jan 2013 to April 2016
- Included: Elective unilateral hip (THA) or knee arthroplasty (TKA), primary or revision
- Excluded:
- Hip or lower limb fracture in previous 3 months
- Metastatic cancer
- Did NOT exclude patients who received ASA pre-op (they could continue open-label ASA <100 mg/d in addition to blinded study drug)
- Baseline characteristics:
- Age 63 y
- Male 48%
- Joint operated: Hip (53%), knee (47%)
- VTE risk factors: Prior VTE 2-3%, previous surgery ~3%, cancer 2-3%, smoker ~9%
- BMI 31
- Post-op mechanical compression: IPCs (50%), graduated stockings (42%), both (8%)
- Hospital LOS 3.5 days
- Peri-op tranexamic acid 54.5%
- Pre-op ASA 25%
Intervention & control
- All patients received rivaroxaban 10 mg once daily on POD #0 (starting >6h after wound closure) or POD #1, & was continued until POD #5
- Intervention: Switched to ASA 81 mg daily on POD #6
- Control: Continued Rivaroxaban 10 mg once daily
- Duration of study drug in both groups:
- Hips x30 days (total 35 days of VTE prophylaxis)
- Knees x9 days (total 14 days of VTE prophylaxis)
Results @ 90 days
- Primary efficacy outcome (symptomatic DVT or PE): ASA 0.6% vs rivaroxaban 0.7%
- Absolute risk difference -0.06% (upper end of 95% confidence interval [CI]: +0.55%), p<0.001 for non-inferiority
- Mortality: 0.06% (1 death from PE) vs 0%
- Primary safety outcome (major or clinically-relevant non-major bleed): 1.3% vs 1.0%
- All consisted of overt bleeding at the surgical site; most occurred between POD #6-16
- Major bleed: 0.5% vs 0.3%
Generalizability (external validity)
- Widely applicable to patients who underwent elective THA/TKA (whether they received DOAC or LMWH from POD #0-5)
Risk of bias: Low (high internal validity)
- Low risk of allocation, performance, detection or attrition bias
- Random sequence generation: using permuted-block design, stratified by THA or TKA, centre, & use of open-label ASA
- Allocation concealment: patients & personnel (central pharmacy staff aware)
- Blinding of patients & personnel: ASA & rivaroxaban administered in identical-appearing opaque gelatin capsules
- Blinding of outcome assessors: Independent adjudication committee unaware of treatment allocation
- ITT analysis
- 1 patient lost to follow-up of VTE, but vital status known (alive @ 90 days)
- Non-inferiority trial design
- Non-inferiority margin set at <1.0% absolute risk difference justified based on survey of Canadian thromboembolism specialists & orthopedic surgeons (reference not provided)
- ITT analysis used for primary analysis; on-treatment analysis consistent with ITT analysis:
- Primary outcome: 0.4% vs 0.4%
- Bleeding: 0.9% vs 0.75%
- No safety advantage for ASA demonstrated in this trial, however, non-inferiority design is justifiable based on substantially-lower cost of ASA (<$5 for 1 month) compared to rivaroxaban ($3/day for 10 mg-tab).
