Sustained Propranolol Use and Site-Specific All-Cause Mortality after Cancer Diagnosis: A Nationwide Taiwan Cohort Study.

Authors

Paul J Chen, Jung-Ju Lin, Wei-Lin Hsu, Der-Cherng Chen, Yu-Hsiang Lin, Chien-Tung Yang, Chao-Hsuan Chen, Yu-Chung Juan, XianXiu Chen

Published in

Oncology research. Volume 34. Issue 11. Pages 15. Epub Oct 28, 2026.

Abstract

Objectives: Drug repurposing offers a low-cost route to expanding cancer therapeutics. β-Adrenergic signalling links physiological stress to tumour progression, and propranolol, a non-selective β-blocker, interrupts this pathway upstream. Existing evidence is drawn predominantly from Western, single-cancer studies, and a comprehensive evaluation of survival across the cancer spectrum within a universal-coverage East Asian population has been lacking. Methods: In this nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database, patients with incident cancer (2010-2020) who received propranolol for at least six consecutive months after diagnosis were compared with non-users frequency-matched 1:4 by sex, age, and index year, yielding 11,500 patients (2300 users; 9200 non-users). All-cause mortality was analysed using Cox proportional hazards regression adjusted for age, sex, and area of residence, with a delayed index-date assignment for non-users intended to reduce temporal imbalance between cancer diagnosis and cohort entry. Pre-specified sensitivity analyses comprised alternative exposure-duration thresholds, propensity score matching, and E-value calculation; site-specific analyses applied false discovery rate control. Results: Over a median follow-up of 4.9 years, propranolol use was associated with lower all-cause mortality (adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.80-0.94), corresponding to 6.7 fewer deaths per 1000 person-years. The E-values for the primary adjusted HR and its upper 95% confidence limit were 1.56 and 1.32, respectively. Estimates across alternative exposure-duration thresholds ranged from 0.90 at three months to 0.83 at twelve months. The association was more evident among men and patients aged ≥ 60 years. Among pre-specified grouped categories, lower mortality was associated with propranolol use in genitourinary (HR 0.50, 95% CI 0.32-0.77) and digestive (HR 0.69, 95% CI 0.56-0.85) system cancers, whereas estimates for lung and liver cancer were near unity; individual cancer-site estimates were exploratory and non-significant after correction. Conclusion: In this nationwide East Asian cohort, sustained propranolol use was associated with lower all-cause mortality, most evident in genitourinary and digestive system cancers. These associations are hypothesis-generating rather than causal, given the observational design and unmeasured confounders including cancer stage and treatment, and support prioritising these categories for prospective evaluation of propranolol as a candidate for oncological repurposing. Because the exposure definition required survival to completion of a six-month treatment window, residual immortal time and selection bias cannot be excluded and the magnitude of the association may be overstated.

PMID:
42985483
Bibliographic data and abstract were imported from PubMed on 05 Nov 2026.

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