The Protective Effects of Aspirin Use from Adverse In Hospital Outcomes and Metastatic Disease in Colorectal Cancer: An Evaluation of the National Inpatient Sample

Introduction Aspirin initially recognized for its anti-inflammatory, antipyretic and analgesic properties hold a prominent role in the treatment of cardiovascular disease. The utility of aspirin in cancer therapeutics has been explored and stratified into COX dependent and independent mechanisms. COX2 gene expression has been demonstrated to be significantly upregulated in colorectal cancer and various other gastrointestinal malignancies including pancreatic, esophageal, and gastric cancer. This study investigates the relationship of aspirin use and outcomes in patients with colorectal cancer. Methodology The Nationwide Inpatient Sample (NIS) database from 2017 to 2022 was analyzed for patients age >18 who were hospitalized for colorectal cancer and its decompensations using ICD-10 diagnostic codes. These patients were further stratified based on the long term use of aspirin. The principal outcome of this investigation is in-hospital mortality, with secondary outcomes including rates of pulmonary embolism, portal vein thrombosis, acute kidney injury and need for renal replacement therapy, septic shock and rates of hepatic, pulmonary, gastrointestinal and peritoneal or retroperitoneal metastatic disease. Multivariate logistic regression accounting for hospital and patient characteristics was implemented for analysis, with the Charlson Comorbidity Index used to adjust for coexisting comorbidity burden; a p-value (p) of <0.05 was considered statistically significant. Results In our analysis of the NIS, 569,306 patients were identified with colorectal cancer and 11.7% (66,608) of this population were identified with long term use of aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.530, p value <0.001 95% CI (confidence interval): 0.460 – 0.617. Patients with aspirin use also demonstrated significantly reduced odds of gastrointestinal, hepatic, pulmonary and retroperitoneal/peritoneal metastasis; (aOR 0.606, 95% CI: 0.564-0.653, P<0.001), (aOR 0.628, 95% CI: 0.582 – 0.678, P<0.001), (aOR 0.676, 95% CI: 0.605 – 0.755, P<0.001) and (aOR 0.751, 95% CI: 0.685 – 0.825, P<0.001) respectively. Conclusion In recent years there has been an alarming increase in incidence of colorectal cancer, particularly amongst younger individuals with increased associated mortality. This mortality increase, albeit alarming, is a driving force for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. COX2 mediated signaling serves as a key promotor of tumorigenic molecular signaling that directly contribute to tumor cell proliferation, angiogenesis and metastasis in colorectal cancer. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced risk of in-hospital mortality. Aspirin use is also linked to a significant reduction in odds of developing metastatic disease to the liver, gastrointestinal system, lungs and peritoneum in patients with colorectal cancer. These findings reveal that aspirin exerts shielding effects against in-hospital mortality and protects patients with colorectal cancer from the development of major comorbid conditions and metastatic disease as compared to those who do not use aspirin.