Is It Time to Comprehensively Utilize Low-Dose Aspirin for Preventing Venous Thromboembolism After Total Knee Arthroplasty?

Commentary The International Consensus Meeting on Venous Thromboembolism (ICM-VTE) in 2022 declared low-dose aspirin as the most effective and safe prophylactic agent for patients undergoing joint arthroplasty1. However, there remains incomplete evaluation regarding its current utilization and safety, particularly for high-risk total knee arthroplasty (TKA) patients. Lavu et al. conducted a comprehensive retrospective analysis using a nationwide database, comparing the efficacy of low-dose aspirin to other anticoagulants following TKA. Their study, which included 126,692 TKA patients from 60 health-care organizations, revealed a significant increase in the proportion of patients receiving low-dose aspirin (from 7.65% to 55.29%) between 2012 and 2022, with the use of other chemoprophylaxis declining accordingly. Notably, both low- and high-risk patients within the low-dose aspirin-only cohorts exhibited reduced odds of deep-vein thrombosis (DVT), pulmonary embolism (PE), bleeding, infections, and hospitalizations compared with alternative prophylactic regimens. Another notable strength of this study lies in its utilization of the most current patient sample, potentially providing insights into the outcomes of emerging outpatient surgery and rapid recovery protocols2. Nevertheless, several considerations emerge when interpreting these findings. First, while the authors evaluated risk across different categories, the definition of high VTE risk in the study appeared vague, potentially overlooking variations in risk severity among high-risk patients, particularly those with preexisting conditions such as atrial fibrillation (AF), a mechanical heart valve, or recent DVT. Those patients often need special attention regarding perioperative anticoagulation therapy, such as bridging anticoagulation therapy for patients with a high thromboembolic risk due to AF3. It is worth noting that, within this cohort, only approximately 15% of patients had a history of prior use of chronic antithrombotic agents, comprising 12% with chronic aspirin usage and 3% with chronic anticoagulant usage across both cohorts, prior to undergoing TKA. Consequently, the current conclusions may not be generalizable to patients with prior use of antithrombotic agents. Furthermore, among patients who chronically use antithrombotic agents before TKA, medication usage may vary over time, particularly for those initially using warfarin who then transition to low-dose aspirin as a prophylactic agent following TKA, and vice versa. Hence, it is crucial to consider the impact of the time-varying exposure pattern among this high-risk population. On the other hand, the authors' contention that low-dose aspirin is a safe and effective prophylactic measure for patients across all risk profiles raises questions regarding dose-dependent differences in risk, particularly among patients with multiple comorbidities. Evaluating the efficacy of low-dose aspirin in patients with various multiple comorbidities through a composite risk categorization approach warrants further investigation. Second, unmeasured confounding remains a challenge in this type of research. While a rise in low-dose aspirin usage coincided with declines in DVT and PE, factors such as the increasing use of ambulatory surgical centers and rapid recovery protocols may have influenced postoperative outcomes. There has been a recent trend toward earlier mobilization of patients postoperatively and earlier discharge to home, which could not be adequately assessed in this study. With the increased utilization of aspirin over the years, a higher proportion of aspirin users relative to other users has been noted in recent years and has been associated with better outcomes. However, bias derived from this trend in exposure over time was not measured and adjusted for in the current study4. Moreover, confounding by indication poses a concern, as clinicians may choose anticoagulation types on the basis of subjective risk assessments not captured in the study data set, potentially biasing the results. For instance, a physician may opt for low-dose aspirin after TKA because of the patient's superior preoperative activity (which is not recorded) and their adoption of rapid recovery protocols, leading the physician to perceive a lower risk of VTE. Addressing these confounders should be a focus of future research endeavors. Specifically, a comprehensive assessment of factors such as year of admission, hospital level, surgeon preference, and socioeconomic status is necessary to properly evaluate their influence on both exposure to antithrombotic agents and related clinical outcomes. Nevertheless, the authors have provided important evidence in the field of prophylaxis for preventing VTE after TKA, and their efforts will become a cornerstone for many future clinical applications and research.