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Table 4 Secondary and sensitivity analyses for pooled analysis of the association between propranolol and non-selective beta-blocker use and breast cancer-specific and all-cause mortality

From: Propranolol and survival from breast cancer: a pooled analysis of European breast cancer cohorts

Medication usage Deaths Patients Person-years Unadjusted Fully adjusted
HR (95% CI) P Hetero I 2 (P) Adjusted HR (95% CI) P Hetero I 2 (P)
Breast cancer-specific mortality
Medication use after diagnosis
Main time-varying covariate analysis in stage 1–3 breast cancer patients
 Propranolol in stages 1–3 3389 44,376 112,450 1.02 (0.82, 1.26) 0.88 0% (0.84) 1.06 (0.85, 1.33) 0.62 0% (0.60)
Main time-varying covariate analysis in all breast cancer patients      
 Any beta-blocker 5419 55,252 181,714 1.25 (1.11, 1.40) <0.001 63% (0.03) 1.07 (0.99, 1.16) 0.10 0% (0.82)
Analysis based upon use in year after diagnosisa
 Propranolol 5426 55,252 181,959 0.94 (0.72, 1.21) 0.61 35% (0.19) 1.07 (0.72, 1.60) 0.72 65% (0.02)
 Non-selective beta-blocker 5426 55,252 181,959 1.10 (0.87, 1.39) 0.43 51% (0.09) 1.15 (0.85, 1.56) 0.35 60% (0.04)
Medication use before diagnosisb
 Propranolol 6883 53,870 215,978 0.97 (0.82, 1.15) 0.73 0% (0.51) 1.03 (0.86, 1.22) 0.78 3% (0.39)
 Non-selective beta-blocker 6883 53,870 215,978 1.09 (0.95, 1.25) 0.22 0% (0.47) 1.05 (0.92, 1.21) 0.45 0% (0.68)
All-cause mortality
Medication use after diagnosis
Main time-varying covariate analysis in stage 1–3 breast cancer patients
 Propranolol in stages 1–3c 17,219 96,097 382,1512 1.07 (0.93, 1.24) 0.32 29% (0.21) 1.13 (1.02, 1.24) 0.02 0% (0.46)
Main time-varying covariate analysis in all breast cancer patients      
 Any beta-blocker 25,472 133,251 570,968 1.57 (1.41, 1.75) <0.001 92% (<0.001) 1.12 (1.05, 1.20) <0.001 65% (0.006)
Analysis based upon use in year after diagnosisa
 Propranolol 25,487 133,251 571,213 1.02 (0.89, 1.16) 0.82 48% (0.06) 1.04 (0.89, 1.21) 0.62 48% (0.06)
 Non-selective beta-blocker 25,487 133,251 571,213 1.35 (1.17, 1.55) <0.001 78% (<0.001) 1.14 (0.99, 1.30) 0.06 68% (0.003)
Medication use before diagnosisb
 Propranolol 31,556 139,760 664,448 0.97 (0.86, 1.09) 0.60 44% (0.09) 1.02 (0.94, 1.10) 0.68 0% (0.54)
 Non-selective beta-blocker 31,556 139,760 664,448 1.30 (1.14, 1.49) <0.001 80% (<0.001) 1.13 (1.06, 1.21) <0.001 27% (0.21)
  1. aSimplified analysis, not requiring time-varying covariate use, comparing medication users with non-users in the first year after diagnosis in individuals living more than 1 year after cancer diagnosis; fully adjusted column adjusted for age, year, stage and all confounders presented in Table 1
  2. bBased on use in the year prior to diagnosis, restricted to individuals with 1 year of records prior to diagnosis; fully adjusted column only adjusted for age at diagnosis and year of diagnosis
  3. cExcludes the Belgian cohort
  4. CI confidence interval, HR hazard ratio