Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis

Abstract

Previous studies have suggested that β-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p < 0.01). In multivariable analysis, beta-blockers usage was not associated with improved survival (Hazard Ratio (HR) 1.04, 95%, Confidence Interval (CI) 0.98–1.1, p = 0.2). When patients were stratified by conditions with indications for beta-blocker usage, such as hypertension, coronary artery disease and cardiac arrhythmia, differences in survival were insignificant compared to non-users in all groups (p > 0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p > 0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8–0.9, p < 0.01). Beta-blocker usage before diagnosis does not confer a survival advantage in patients with PDAC, though continuous use before and after diagnosis did confer a survival advantage. Prospective studies into the mechanism for this advantage are needed.

The prevalence and impact of overweight and hypertension among patients with pancreatic cancer

“…A meta-analysis by Jiang et al (2022) [27] confirmed that the use of anti-hypertensive medication (ACEIs/ARBs, CCBs, diuretics, β-blockers) does not have a negative effect on overall survival of PC patients; thus, they should continue to use these drugs to prevent cardiovascular events. Yang et al (2021) [28] suggested that β-blockers usage before PC diagnosis is not correlated with survival advantage; nevertheless, continuous use before and after diagnosis presented survival benefits. The mechanism remains unclear, and the authors noted the need for further prospective studies [28].…”

Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

“…In a preclinical study (NCT00502684), β-blockers, such as propranolol/propranolol hydrochloride, reduced PDAC-specific mortality [ 10 ]. In a multivariable analysis, treatment with beta-blockers did not improve survival in PDAC patients [ 77 ]. Using an in vivo model of PNI, it was possible to show that cancer cells’ neural spreading might be treated by the administration of an attenuated, replication-competent, oncolytic herpes simplex virus.…”

Neural Component of the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma

“…Results regarding the overall survival of patients with PDAC who used β-blockers were inconsistent [ 98 , 99 ]. A Swedish general population-based cohort study demonstrated that β-blocker use may have a beneficial effect on survival among PDAC patients [ 98 ].…”

“…A Swedish general population-based cohort study demonstrated that β-blocker use may have a beneficial effect on survival among PDAC patients [ 98 ]. Nevertheless, a US-based epidemiological study determined that no β-blocker treatment, even after stratification by receptor selectivity, lasting for six months before diagnosis, improved survival in pancreatic cancer [ 99 ]. However, according to the same study, continuous β-blocker usage within 12 months surrounding PDAC diagnosis conferred significant improvement in overall survival [ 99 ].…”