by Elizabeth Hofheinz, M.P.H., M.Ed., February 12, 2020
In one form or another, chemists through the ages have been experimenting with aspirin. When it comes to rubber stamping this ancient treatment for preventing complications following total hip (THA) and knee (TKA) arthroplasty, however, the experimentation should continue, says at least one hip and knee surgeon.
Richard Iorio, M.D. is Chief of the Adult Reconstruction and Total Joint Arthroplasty Service in the Department of Orthopaedic Surgery at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Iorio told OSN, “There is a long history of debate between the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) when it comes to appropriate preventive measures for venous thromboembolism (VTE) after total joint surgery. In 2012 the two organizations came together to declare that the occurrence of bleeding deserved more attention, with both parties declaring that with clinically significant pulmonary embolism (PE) as the vital endpoint, there were insufficient data to endorse any specific prophylaxis regimen over another.”
So when three clinical studies emerged in the 2019 literature, Dr. Iorio and colleagues from multiple centers were, well, intrigued. They soon published, “Selection Bias, Orthopaedic Style: Knowing What We Don’t Know About Aspirin,” which appears in the December 31, 2019 edition of The Journal of Bone and Joint Surgery.
“Each of these 2019 clinical studies essentially declared that aspirin was finally proven to be the best option to prevent VTE following THA and TKA. One of the problems was that each study utilized retrospective observational data from the time period when surgeons were choosing aspirin for all patients except those deemed at the highest possible risk level. The patients involved were specifically selected to receive some kind of prophylaxis other than aspirin if they were considered to be at higher risk than other TJA patients. This points to a selection bias that highlights the effectiveness of aspirin and sheds doubt on the outcomes for other anticoagulants.”
Show me the prospective randomized clinical trials…
Dr. Iorio: “What we lack is a study involving patients at similar risk levels who are randomly assigned to receive either aspirin (ASA) or a potent anticoagulant.”
But data is on the way…
The Pulmonary Embolism Prevention after Hip and Knee Replacement trial (PEPPER), a 20,000-person study funded by the Patient Centered Outcomes Research Institute (PCORI), began in 2015 and will run to 2024. Dr. Iorio: “This randomized trial, led by principal investigator Vincent Pellegrini, M.D. of the Dartmouth-Hitchcock Clinic, involves 25 medical centers around the country that are comparing aspirin, warfarin, and rivaroxaban for use after total joint surgery.”
“Years ago, we noticed that many TJA patients remained in bed too long postoperatively and were thus not rapidly mobilizing. These patients were at higher risk for venous thromboembolic disease (VTED) and were thought to require aggressive anticoagulation.”
Thus, says Dr. Iorio, began the era of painting with a broad brush. “Many surgeons began treating every TJA patient aggressively, assuming they die from a PE. Meanwhile, however, such treatment put them at risk for bleeding and infection.”
Then we moved to the era of rapid rehab protocols, and the trend of not using aggressive anticoagulants on these patients. “Currently, aggressive anticoagulants are frowned upon in most patients because of the bleeding and infection complications that can occur. We also found that a small subset of patients likely had a genetic predisposition to clots, may not respond to traditional VTED prophylaxis and may require aggressive anti-coagulation and other interventions to prevent fatal pulmonary embolism. It’s unclear if ASA is sufficient for VTED prophylaxis in most patients or if most patients in this age of rapid recovery will be fine with any regimen. These are high risk individuals who likely need something different, but we can’t yet identify who they are. While genetic testing is an option, it is quite expensive and not definitive.”
And the fundamental issue that Dr. Iorio wants to highlight? “This trial essentially begs for surgeons to wait for definitive answers about the most appropriate prophylaxis. Once complete, we will be able to definitively say which of the three does the least harm. At this point we have roughly 10,000 people enrolled. We do not know yet which arm of the trial has the best efficacy or the least complications. It is too soon to declare ASA the winner.”
“Interestingly, PE is seen by patients as an act of God (i.e., not the surgeon’s fault), whereas infection or bleeding is believed to be within the control of the surgeon. Ultimately, the PEPPER study will help us gain clarity on this complex issue.”
