Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta‐analysis of observational studies

• Published in: Pharmacoepidemiology and drug safety 2018-03, Vol.27 (3), p.279-288
• Main Authors: Tang, Huilin, Fu, Shuangshuang, Zhai, Suodi, Song, Yiqing, Asgari, Maryam M., Han, Jiali
• Format: Article
• Language: English
• Subjects: Angiotensin-converting enzyme inhibitors; Antihypertensive Agents - adverse effects; antihypertensive drugs; Antihypertensives; Basal cell carcinoma; Calcium; Carcinoma, Basal Cell - chemically induced; Carcinoma, Basal Cell - epidemiology; Carcinoma, Basal Cell - pathology; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - pathology; Diuretics; Epidemiology; Humans; Hypertension - drug therapy; Inhibitors; keratinocyte carcinoma; Keratinocytes - drug effects; Keratinocytes - pathology; Meta-analysis; Observational studies; Observational Studies as Topic; pharmacoepidemiology; Pharmacology; Skin cancer; Skin Neoplasms - chemically induced; Skin Neoplasms - epidemiology; Skin Neoplasms - pathology; Squamous cell carcinoma
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.4384

Purpose Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta‐analysis of observational studies. Methods We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta‐adrenergic blocking agents (β‐blockers), and calcium channel blockers (CCBs). Random‐effects meta‐analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Results Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01‐1.20) and SCC (OR, 1.40; 95% CI, 1.19‐1.66). Use of β‐blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with β‐blockers was 1.09 (95% CI, 1.04‐1.15) and with CCBs was 1.15 (95% CI, 1.09‐1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39‐0.71) and SCC (OR, 0.58; 95% CI, 0.42‐0.80) in high‐risk individuals. Conclusions Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high‐risk individuals. β‐blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.