Beneficial Prognostic Effects of Aspirin in Patients Receiving Sorafenib for Hepatocellular Carcinoma: A Tale of Multiple Confounders

Abstract

Case–control observational studies suggested that aspirin might prevent hepatocellular carcinoma (HCC) in high-risk patients, even if randomized clinical trials are lacking. Information regarding aspirin in subjects who already developed HCC, especially in its advanced stage, are scarce. While aspirin might be a low-cost option to improve the prognosis, multiple confounders and safety concerns are to be considered. In our retrospective analyses of a prospective dataset (n = 699), after assessing the factors associated with aspirin prescription, we applied an inverse probability treatment weight analysis to address the prescription bias. Analyses of post-sorafenib survival were also performed to reduce the influence of subsequent medications. Among the study population, 133 (19%) patients were receiving aspirin at the time of sorafenib prescription. Aspirin users had a higher platelet count and a lower prevalence of esophageal varices, macrovascular invasion, and Child–Pugh B status. The benefit of aspirin was confirmed in terms of overall survival (HR 0.702, 95% CI 0.543–0.908), progression-free survival, disease control rate (58.6 vs. 49.5%, p < 0.001), and post-sorafenib survival even after weighting. Minor bleeding events were more frequent in the aspirin group. Aspirin use was associated with better outcomes, even after the correction for confounders. While safety concerns arguably remain a problem, prospective trials for patients at low risk of bleeding are warranted.

Durable objective response to sorafenib and role of sequential treatment in unresectable hepatocellular carcinoma

“…Aspirin use was reported in association with better clinical outcomes and survival benefits in patients who received sorafenib treatment for HCC. 36 As to our patients, none of sorafenib-responders had used aspirin during the sorafenib or subsequent therapies for HCC. Therefore, we did not include aspirin use in the analysis.…”

Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study

“…A previous study has reported that aspirin, a low-cost medication for cardiovascular protection, was associated with reduced incidence of and lower mortality from HCC in patients with viral hepatitis infection [28]. Ielasi et al also reported recently that aspirin use could improve survival in HCC patients who received sorafenib treatment [29]. Statins could also benefit patients with reduced risk of recurrence and improved survival after a surgical resection or liver transplant [30].…”

Outcomes of Sorafenib for Recurrent Hepatocellular Carcinoma After Liver Transplantation in the Era of Combined and Sequential Treatments

“…34 Chronic use of low-dose aspirin has been recently advocated as a positive predictive factor in sorafenib-treated patients. 21,22 Its extensive use in LT patients to prevent the occlusion of the hepatic artery anastomosis 34 could be another factor contributing to the OS values. Second, the preserved liver function and good performance status allowed a more frequent use of combined locoregional treatments during and Copyright © 2022 Wolters Kluwer Health, Inc.…”