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Pulmonary Embolism Prevention Trial - PEP
Description:
The Pulmonary Embolism Prevention Trial (PEP) was a randomized clinical trial designed to test whether aspirin reduces in-hospital morbidity due to venous thromboembolism in high-risk patients undergoing surgery for hip fracture and elective hip or knee arthroplasty.
Hypothesis:
Patients at high risk for venous thromboembolism receiving perioperative low-dose aspirin would have improved in-hospital morbidity and mortality from venous thromboembolism.
Study Design
Study Design:
Patients Enrolled: 17,444
Mean Follow Up: 35 days
Mean Patient Age: mean 79
Female: 79
Patient Populations:
Patients with a femoral-neck fracture or other fracture of the proximal femur were potentially eligible for the trial in all participating countries. In New Zealand, patients undergoing elective hip or knee arthroplasty were also eligible. The fundamental eligibility criterion was the treating doctor’s uncertainty as to the balance of benefits and risks of low-dose aspirin for the particular patient.
Exclusions:
Patients with a clear indication for aspirin (e.g., recent MI) or clear contraindication to aspirin (e.g., active peptic ulcer). The use of other prophylactic measures (e.g., subcutaneous heparin) did not preclude entry in the trial, nor did previous use of aspirin or other NSAIDs.
Primary Endpoints:
In-hospital venous thromboembolism (symptomatic DVT, PE)
Secondary Endpoints:
Vascular and nonvascular in-hospital morbidity; 35-day mortality; and in-hospital bleeding complications
Drug/Procedures Used:
Five weeks of 160 mg enteric-coated aspirin or matching placebo. Study treatment was to be continued daily until completion of the 35-day course (or prior death), unless a clear indication for, or a clear contraindication to, aspirin was judged to have developed.
Concomitant Medications:
Avoidance of nonstudy aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) unless specifically indicated
Principal Findings:
A total of 13,356 patients with hip fracture and 2,648 patients undergoing elective hip or knee arthroplasty were enrolled. Baseline characteristics were well-balanced between the study arms. Overall, the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT) was reduced by 34% in the patients treated with aspirin (p=0.0003).
In patients with hip fracture, PE, DVT, or both was confirmed in 1.6% of aspirin-treated patients and 2.5% of placebo-treated patients (36% relative reduction, p=0.0003). Similar statistically significant reductions were seen when PE, fatal PE, and DVT were considered as individual endpoints. Reductions in venous thromboembolism were also seen in aspirin-treated patients treated with heparin.
There were slightly more bleeding complications in aspirin-treated patients (2.9% incidence of any postoperative bleeding episode vs. 2.3% in the placebo group, p=0.04). Although there was no statistically significant effect of aspirin in the group of patients undergoing hip or knee arthroplasty, the effect of size of aspirin in this subgroup appeared to be similar to the overall group.
Interpretation:
This trial demonstrates that low-dose aspirin was associated with a reduction in in-hospital risk of venous thromboembolism in patients undergoing surgery for hip fracture and knee and hip arthroplasty. To what extent aspirin is efficacious in this regard compared to other strategies such as low molecular weight heparin and warfarin therapy was not addressed in this study.
References:
Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet 2000;355:1295-302.
Keywords: Arthroplasty, Replacement, Hip, Thromboembolism, Platelet Aggregation Inhibitors, Heparin, Low-Molecular-Weight, Pulmonary Embolism, Warfarin, Venous Thromboembolism, Venous Thrombosis, Hip Fractures, Risk Assessment
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