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Table 3 Sensitivity and subgroup analyses for furosemide use and esophageal cancer-specific mortality

From: Furosemide use and survival in patients with esophageal or gastric cancer: a population-based cohort study

  Non-users Users Unadjusted HR (95% CI) Adjusteda HR (95% CI)
  Patients Deaths Person-years Patients Deaths Person-years
All patientsb
 Main analysis 2365 1625 4336 343 219 471 1.47 (1.27, 1.69) 1.28 (1.10, 1.50)
 All cancer death 2365 1730 4336 343 248 471 1.56 (1.36, 1.78) 1.34 (1.16, 1.55)
 All cause death 2365 1784 4336 343 277 471 1.68 (1.47, 1.90) 1.44 (1.25, 1.65)
 Use in the year before diagnosis 3862 2836 5739 567 438 469 1.46 (1.32, 1.62) 1.14 (1.02, 1.28)
 12 month lag 1481 883 3401 208 112 336 1.56 (1.28, 1.90) 1.41 (1.13, 1.75)
Tumor typec
 Adenocarcinoma 1478 1015 2837 218 145 322 1.55 (1.30, 1.85) 1.30 (1.07, 1.57)
 Squamous cell carcinoma 717 496 1214 99 59 115 1.38 (1.05, 1.81) 1.64 (1.18, 2.26)
 Additionally adjusted for smoking and alcohold 1391 1031 1581 182 134 173 1.34 (1.11, 1.60) 1.12 (0.91, 1.36)
 Additionally adjusted for BMIe 1448 1036 1928 218 148 243 1.25 (1.05, 1.49) 1.09 (0.90, 1.32)
 All loop diureticsf 2348 1613 4313 360 231 492 1.44 (1.25, 1.66) 1.24 (1.06, 1.44)
 Additionally adjusted for stageg 473 285 641 47 26 62 1.24 (0.83, 1.86) 1.19 (0.74, 1.91)
 Additionally adjusted for gradeh 1775 1229 3131 246 164 312 1.55 (1.31, 1.82) 1.44 (1.20, 1.73)
 Restricted to patients with high grade diagnosisi 908 661 1371 98 70 113 1.55 (1.21, 1.99) 1.36 (1.04, 1.79)
 Restricted to patients surgically treatedj 959 579 2460 125 70 248 1.64 (1.28, 2.11) 1.44 (1.10, 1.90)
 Restricted to any hypertensive medication usek 1062 736 1676 264 174 335 1.34 (1.13, 1.58) 1.13 (0.94, 1.36)
 Furosemide vs other antihypertensive medicationl 1106 771 1909 343 219 471 1.46 (1.25, 1.70) 1.27 (1.07, 1.49)
 Year of diagnosism: 1998 to 2002 482 372 1095 85 58 131 1.72 (1.30, 2.27) 1.46 (1.06, 1.99)
 2003 to 2007 789 601 1701 123 80 179 1.45 (1.15, 1.84) 1.28 (0.99, 1.65)
 2008 to 2013 1094 652 1540 135 81 162 1.32 (1.05, 1.67) 1.22 (0.94, 1.59)
Restricted to any diagnosis of hypertension/edema/MI/HFn
 Main analysis 1097 763 1747 233 148 285 1.29 (1.08, 1.55) 1.07 (0.88, 1.30)
 12 month lag 683 422 1314 138 75 194 1.31 (1.02, 1.68) 1.04 (0.79, 1.37)
Tumor typeo
 Adenocarcinoma 715 493 1192 146 98 188 1.43 (1.14, 1.78) 1.08 (0.85, 1.39)
 Squamous cell carcinoma 310 214 471 71 41 78 1.18 (0.85, 1.66) 1.32 (0.87, 2.00)
 Additionally adjusted for smoking and alcohold 758 567 785 137 97 137 1.15 (0.92, 1.43) 0.95 (0.74, 1.21)
 Additionally adjusted for BMIe 774 562 900 162 107 182 1.03 (0.83, 1.27) 0.83 (0.65, 1.05)
 All loop diureticsf 1082 752 1730 248 159 302 1.28 (1.08, 1.52) 1.03 (0.84, 1.25)
 Additionally adjusted for Stageg 275 160 351 33 17 32 1.29 (0.78, 2.14) 1.37 (0.76, 2.48)
 Additionally adjusted for Gradeh 832 578 1328 172 112 211 1.41 (1.15, 1.72) 1.25 (0.99, 1.57)
 Year of diagnosisp: 1998 to 2002 149 120 290 43 30 47 1.47 (0.98, 2.20) 1.07 (0.65, 1.77)
 2003 to 2007 348 279 685 83 58 112 1.34 (1.01, 1.79) 1.12 (0.81, 1.54)
 2008 to 2013 600 364 772 107 60 126 1.16 (0.88, 1.52) 0.99 (0.72, 1.36)
  1. aAdjusted for age at diagnosis, sex, year of diagnosis, deprivation, radiotherapy within 6 months, chemotherapy within 6 months, surgery within 6 months, comorbidities (prior to diagnosis, including cerebrovascular disease, chronic pulmonary disease, congestive heart disease, diabetes, myocardial infarction, peptic ulcer disease, peripheral vascular disease, renal disease, rheumatological disease and liver disease), and other medication use (statins, aspirin, time-varying after diagnosis)
  2. bSensitivity analyses based on the primary main analyses, including all eligible patients except were indicated
  3. cP-value for interaction for esophageal cancer is 0.794
  4. dRestricted to patient with smoking and alcohol records
  5. eRestricted to patient with BMI records
  6. fAssociation between all loop diuretics (including furosemide, bumetanide and torasemide) use after diagnosis and gastric or esophageal cancer mortality
  7. gAdditionally adjusted for tumor stage
  8. hAdditionally adjusted for tumor grade
  9. iRestricted to patients who were diagnosed as grade 3 or 4 cancer
  10. jRestricted to patients who received the surgery treatment within 6 months of diagnosis
  11. kRestricted to patients with any antihypertensive medication use in the year prior to cancer diagnosis
  12. lUsing other antihypertensive medications after cancer diagnosis as an active comparator
  13. mP-value for interaction across cancer diagnosis year is 0.265
  14. nRestricted to patients with any diagnosis of hypertension, edema, myocardial infarction or heart failure at any time prior to esophageal cancer diagnosis
  15. oP-value for interaction for esophageal cancer is 0.524
  16. pP-value for interaction across cancer diagnosis year is 0.964
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