S A J Schmidt1,2, M Schmidt1,2, F Mehnert1, S Lemeshow1,2, H T Sørensen1. 1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 2. Division of Biostatistics, College of Public Health, Ohio State University, Columbus, OH, USA.
Abstract
BACKGROUND: Several antihypertensive drugs are photosensitizing and may therefore act as cocarcinogens with ultraviolet radiation. OBJECTIVE: To examine whether antihypertensive drug use is associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: We used population-based databases to conduct a case-control study including all first-time cases of SCC (n = 2282), BCC (n = 17,242), and MM (n = 3660) in northern Denmark, 1991-2010. We matched approximately 10 controls (n = 231,743) to each case by age, sex and county using risk-set sampling. We used conditional logistic regression to compute odds ratios (ORs) for skin cancer with 95% confidence intervals comparing ever users of antihypertensives (>2 previous prescriptions) with non-users (≤2 previous prescriptions). We adjusted for comorbidity and comedications. We further analysed use by duration (short term: <5 years; long term: ≥5 years) and intensity (low intensity or high intensity: <50% or ≥50% prescription coverage during total duration of use, respectively). RESULTS: Ever users of diuretics were at increased risk of SCC (OR 1.19; 1.06-1.33), driven by potassium-sparing agents alone (OR 1.40; 1.09-1.80) or with low-ceiling diuretics (OR 2.68; 2.24-3.21) and by long-term use (OR 1.41; 1.16-1.72 at low intensity; OR 1.44; 0.98-2.14 at high intensity). Ever users of sulphonamides (OR 1.49; 1.04-2.12) and non-aldosterone antagonist potassium-sparing agents (OR 2.26; 0.85-6.01) were at increased MM risk. The latter was also associated with BCC (OR 1.47; 1.00-2.17), as was low-ceiling diuretics combined with potassium-sparing agents (OR 1.23; 1.12-1.35). Long-term, low-intensity (OR 1.53; 1.05-2.23) and high-intensity (OR 1.44; 0.56-3.69) angiotensin receptor blocker use was associated with MM. Estimates for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers were inconsistent or weak (<20% increased). CONCLUSION: Long-term angiotensin receptor blocker use was associated with risk of MM. Moreover, long-term diuretic use was associated with SCC risk, driven by potassium-sparing agents alone or in combination with low-ceiling diuretics.
BACKGROUND: Several antihypertensive drugs are photosensitizing and may therefore act as cocarcinogens with ultraviolet radiation. OBJECTIVE: To examine whether antihypertensive drug use is associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: We used population-based databases to conduct a case-control study including all first-time cases of SCC (n = 2282), BCC (n = 17,242), and MM (n = 3660) in northern Denmark, 1991-2010. We matched approximately 10 controls (n = 231,743) to each case by age, sex and county using risk-set sampling. We used conditional logistic regression to compute odds ratios (ORs) for skin cancer with 95% confidence intervals comparing ever users of antihypertensives (>2 previous prescriptions) with non-users (≤2 previous prescriptions). We adjusted for comorbidity and comedications. We further analysed use by duration (short term: <5 years; long term: ≥5 years) and intensity (low intensity or high intensity: <50% or ≥50% prescription coverage during total duration of use, respectively). RESULTS: Ever users of diuretics were at increased risk of SCC (OR 1.19; 1.06-1.33), driven by potassium-sparing agents alone (OR 1.40; 1.09-1.80) or with low-ceiling diuretics (OR 2.68; 2.24-3.21) and by long-term use (OR 1.41; 1.16-1.72 at low intensity; OR 1.44; 0.98-2.14 at high intensity). Ever users of sulphonamides (OR 1.49; 1.04-2.12) and non-aldosterone antagonist potassium-sparing agents (OR 2.26; 0.85-6.01) were at increased MM risk. The latter was also associated with BCC (OR 1.47; 1.00-2.17), as was low-ceiling diuretics combined with potassium-sparing agents (OR 1.23; 1.12-1.35). Long-term, low-intensity (OR 1.53; 1.05-2.23) and high-intensity (OR 1.44; 0.56-3.69) angiotensin receptor blocker use was associated with MM. Estimates for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers were inconsistent or weak (<20% increased). CONCLUSION: Long-term angiotensin receptor blocker use was associated with risk of MM. Moreover, long-term diuretic use was associated with SCC risk, driven by potassium-sparing agents alone or in combination with low-ceiling diuretics.
Authors: Beatrice Nardone; Sara Majewski; Ashley S Kim; Tina Kiguradze; Estela M Martinez-Escala; Rivka Friedland; Ahmad Amin; Anne E Laumann; Beatrice J Edwards; Alfred W Rademaker; Mary C Martini; Dennis P West Journal: Drug Saf Date: 2017-03 Impact factor: 5.606