(C-216) Diuretics are associated with rates of basal and squamous cell carcinomas of the skin in the U.S. Medicare population with hypertension

Background: Diuretics are commonly prescribed for hypertension but increase skin photosensitivity to ultraviolet radiation (UVR), an important risk factor for keratinocyte cancer (KC), including basal (BCC) and squamous (SCC) cell carcinoma. Little is known about how UVR modify susceptibility to BCC and SCC among patients on diuretics.

Objectives: To examine the association between common types of diuretics and risk for BCC and SCC accounting for UVR exposure

Methods: We conducted a cohort study using data from U.S. Medicare. We included non–Hispanic White individuals ages 66– < 85 with a diagnosis of hypertension 1/1/2012 (baseline; N=6,539,996). We followed patients from 1/1/2012, to the earliest event: KC diagnosis, death, lost coverage of Part A/B/non–Health Maintenance Organization (HMO), switching to HMO, turning 85-years-old, or end of study (12/31/2018). Satellite–based ambient UVR was linked to patients’ zip codes at baseline. Time–dependent duration of diuretic use was based on Part D prescription claims. KCs were ascertained using administrative diagnoses and procedure codes. To examine the association between major types of diuretics and risks of BCC and SCC, we used Poisson regression models to calculate excess relative rates (ERRs) and 95% confidence intervals (CIs). To examine whether ambient UVR (low: 2– < 35 J/m2 versus high: 35–84 J/m2) modified the associations of four common types of diuretics, we conducted likelihood–ratio tests for multiplicative interaction.

Results: There were 778,705 BCCs and 615,178 SCCs diagnosed during 30 million person–years. KC incidence was increased per year of use for hydrochlorothiazide (ERR=0.008; 95% CI=0.007,0.009 for BCC; ERR=0.024; 95% CI=0.023,0.025 for SCC), furosemide (ERR=0.009; 95% CI=0.007,0.010 for BCC; ERR=0.041; 95% CI=0.039,0.043 for SCC), and triamterene (ERR=0.010; 95% CI=0.008,0.012 for BCC; ERR=0.041; 95% CI=0.039,0.043 for SCC). SCC but not BCC incidence was reduced per year of use for chlorthalidone (ERR=-0.010; 95% CI=-0.014,-0.005). While ambient UVR modified positive associations for hydrochlorothiazide and triamterene (all P values for interaction < 0.001), increased KCs rates remained for hydrochlorothiazide, furosemide and triamterene in patients with low and high UVR.

Conclusions: Patients with claims of hydrochlorothiazide, furosemide or triamterene had increased KC rates, independent of UVR. However, patients with chlorthalidone claims did not have increased SCC rate. Considerations in interpreting the diuretic-KCs associations include lack of information before age 65 about diuretic use, prior history of KCs, and potential misclassification of individual UVR exposure using the proxy of ambient UVR levels.