Digoxin use and the risk for colorectal cancer

Purpose: Cardiac glycosides affect several pathways central for tumor formation. We sought to evaluate the association between digoxin use and colorectal cancer (CRC) risk. Methods: We conducted a nested case-control study using The Health Improvement Network (THIN), a medical record database representative of the broader UK population. Study cases were defined as those with a diagnostic code for CRC. Each case was matched to up to four eligible controls on age, sex, practice site, and duration of follow-up before index date using incidence density sampling. Exposure of interest was digoxin therapy before index date. The odds ratios (ORs) and 95% confidence intervals (CIs) for CRC associated with digoxin use were estimated using conditional logistic regression analysis, adjusted for BMI, alcoholism, smoking history, diabetes mellitus, heart disease, chronic NSAIDs use and previous screening colonoscopies. Results: The case-control analysis included 20990 CRC patients and 82054 controls whose mean follow-up time before index date was 6.5years (SD 4.0). The adjusted OR for CRC among current digoxin users was increased compared with non-users with an adjusted ORs of 1.41 (95%CI 1.25-1.59, p<0.0001), 1.45 (95%CI 1.22-1.72, p<0.0001) and 1.41 (95%CI 1.00-1.99, p=0.049) for first prescriptions 1-5years, 5-10years and more than 10years before index date respectively. Similar results were observed when cumulative duration and number of digoxin prescriptions were analyzed. The risk was not elevated for past digoxin users. Conclusions: Current digoxin use is associated with increased CRC risk.