A cohort study of digoxin exposure and mortality in men with prostate cancer.
OBJECTIVE
To examine the association between digoxin exposure and mortality in men with prostate cancer using linked Irish National Cancer Registry and pharmacy claims data.


METHODS
Prostate cancer cases were identified from the database and digoxin exposure at prostate cancer diagnosis was identified from prescription claims. Digoxin users were matched to non-users using a propensity score to identify men with similar cardiovascular comorbidity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between digoxin exposure and all-cause and prostate cancer-specific mortality (PCSM). Analyses were repeated in the propensity score-matched cohort. Effect modification of treatment with radiation or androgen-deprivation therapy by digoxin exposure was also assessed.


RESULTS
In all, 5732 men with a prostate cancer diagnosis (2001-2006) were identified (digoxin exposed, 391). The median follow-up was 4.3 years. Digoxin exposure was associated with a small non-significant increase in PCSM in the full cohort (HR 1.13, 95% CI 0.91, 1.42) and the propensity. score-matched cohort (HR 1.17, 95% CI 0.88, 1.57). Adjusted HRs for all-cause mortality were increased for digoxin exposed men (HR 1.24, 95% CI 1.07, 1.43). Interactions with treatments received were not significant.


CONCLUSIONS
These results suggest digoxin exposure is not associated with reduced PCSM. Further investigation of other cardiac glycosides that have shown anti-cancer potential may be warranted.
Department of Pharmacology and Therapeutics, Trinity College, University of Dublin, Dublin, Ireland.
Evelyn M
EM
Flahavan
Linda
L
Sharp
Kathleen
K
Bennett
Thomas I
TI
Barron
D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D002423:Cause of Death; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000889:Anti-Arrhythmia Agents; D014408:Biomarkers, Tumor; D002316:Cardiotonic Agents; D004077:Digoxin; D017430:Prostate-Specific Antigen
cardiac glycoside; digoxin; hypoxia-inducible factor 1α; mortality; propensity score; prostate neoplasms