Beta blockers and cancer prognosis – The role of immortal time bias: A systematic review and meta-analysis

• Previous findings have suggested enhanced cancer survival among beta blocker users.
• Our results suggest no benefit of beta blocker use among cancer patients.
• The proposed beneficial effect might be based on immortal time bias.

BackgroundFindings from experimental and observational studies have suggested beneficial effects of beta blocker (BB) use on cancer survival. Nevertheless, results have been inconclusive and there have been concerns that the observed associations might have resulted from immortal time bias (ITB). We conducted a systematic review and meta-analysis to summarize existing evidence, paying particular attention to this potential source of bias.MethodsA systematic literature search was performed in PubMed and Web of Science. Studies investigating the association between BB use and overall or cancer-specific survival were included. Summary estimates were derived from meta-analyses using random effects models. The potential influence of ITB was investigated.ResultsWe identified 30 eligible studies including 88,026 cancer patients in total. We deemed 11 studies to be at high or unclear risk of ITB. Including all studies in the meta-analysis, BB users had a significantly better overall (hazard ratio (HR) 0.88, 95% CI 0.79–0.97) and cancer-specific (HR 0.75, 95% CI 0.64–0.88) survival. Excluding the studies deemed to be prone to ITB resulted in HRs (95% CIs) of 1.00 (0.93–1.07) and 0.90 (0.83–0.98), respectively. Analyses on cancer site and BB type did not show beneficial associations besides overall survival among melanoma patients. However, melanoma-specific survival was not improved.ConclusionWe found no clinically meaningful evidence for an association between BB use and survival after excluding studies with a possible ITB. Our results support suggestions that the proposed beneficial effect of BBs on cancer survival might be based on ITB.