Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides

A Matched Cohort Study

Beatrice Nardone, Sara Majewski, Ashley S. Kim, Tina Kiguradze, Estela M. Martinez-Escala, Rivka Friedland, Ahmad Z Amin, Anne E Laumann, Beatrice J. Edwards, Alfred W Rademaker, Mary C. Martini, Dennis P West*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Introduction: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Objective: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. Methods: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Results: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35). Conclusions: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

Original languageEnglish (US)
Pages (from-to)249-255
Number of pages7
JournalDrug Safety
Volume40
Issue number3
DOIs
StatePublished - Mar 1 2017

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Thiazides
Angiotensin Receptor Antagonists
Skin Neoplasms
Angiotensin-Converting Enzyme Inhibitors
Melanoma
Skin
Cohort Studies
Odds Ratio
Squamous Cell Carcinoma
Confidence Intervals
International Classification of Diseases
Logistics
Logistic Models
Electronic medical equipment
Data warehouses
Electronic Health Records
Epithelial Cells
Health Personnel
Population
Medicine

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Nardone, Beatrice ; Majewski, Sara ; Kim, Ashley S. ; Kiguradze, Tina ; Martinez-Escala, Estela M. ; Friedland, Rivka ; Amin, Ahmad Z ; Laumann, Anne E ; Edwards, Beatrice J. ; Rademaker, Alfred W ; Martini, Mary C. ; West, Dennis P. / Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides : A Matched Cohort Study. In: Drug Safety. 2017 ; Vol. 40, No. 3. pp. 249-255.
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title = "Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study",
abstract = "Introduction: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Objective: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. Methods: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Results: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95{\%} confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95{\%} CI 2.13–3.83), ACEIs (OR 2.23; 95{\%} CI 1.78–2.81) and TZs (OR 2.11; 95{\%} CI 1.60–2.79); SCC and ARBs (OR 2.22; 95{\%} CI 1.37–3.61), ACEIs (OR 1.94; 95{\%} CI 1.37–2.76), and TZs (OR 4.11; 95{\%} CI 2.66–6.35). Conclusions: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.",
author = "Beatrice Nardone and Sara Majewski and Kim, {Ashley S.} and Tina Kiguradze and Martinez-Escala, {Estela M.} and Rivka Friedland and Amin, {Ahmad Z} and Laumann, {Anne E} and Edwards, {Beatrice J.} and Rademaker, {Alfred W} and Martini, {Mary C.} and West, {Dennis P}",
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doi = "10.1007/s40264-016-0487-9",
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Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides : A Matched Cohort Study. / Nardone, Beatrice; Majewski, Sara; Kim, Ashley S.; Kiguradze, Tina; Martinez-Escala, Estela M.; Friedland, Rivka; Amin, Ahmad Z; Laumann, Anne E; Edwards, Beatrice J.; Rademaker, Alfred W; Martini, Mary C.; West, Dennis P.

In: Drug Safety, Vol. 40, No. 3, 01.03.2017, p. 249-255.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides

T2 - A Matched Cohort Study

AU - Nardone, Beatrice

AU - Majewski, Sara

AU - Kim, Ashley S.

AU - Kiguradze, Tina

AU - Martinez-Escala, Estela M.

AU - Friedland, Rivka

AU - Amin, Ahmad Z

AU - Laumann, Anne E

AU - Edwards, Beatrice J.

AU - Rademaker, Alfred W

AU - Martini, Mary C.

AU - West, Dennis P

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Introduction: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Objective: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. Methods: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Results: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35). Conclusions: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

AB - Introduction: Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Objective: The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. Methods: This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Results: Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35). Conclusions: A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

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