Hydrochlorothiazide use and the risk of skin cancer (Q19-05)

Hydrochlorothiazide use and the risk of skin cancer (Q19-05)

Hydrochlorothiazide use and the risk of skin cancer (Q19-05)

Q19-05

Overview

What is the issue?
  • Hydrochlorothiazide (HCTZ), a thiazide diuretic, is among the most prescribed antihypertensive drugs.
  • Some studies have suggested that HCTZ can potentially increase the risk of skin cancer.
What was the aim of the study?
  • To determine if there is an association between the use of HCTZ and the risk of keratinocyte carcinoma and melanoma compared with angiotensin-converting enzyme inhibitors (ACEIs) or calcium channel blockers (CCBs), two other classes of drugs used in the first-line treatment of hypertension.
How was the study conducted?
  • We conducted a multi-site population-based cohort study using administrative health databases from six Canadian provinces and the United States (US) MarketScan® Commercial and Medicare databases.
  • The study cohorts included patients aged 40 years and older newly treated with HCTZ or a clinically relevant comparator, ACEIs in the primary comparison or CCBs in the secondary comparison, between 1995 and 2018.
  • The risk of keratinocyte carcinoma and melanoma was compared between new users of HCTZ and new users of ACEIs and CCBs separately. Results were combined using a statistical approach called meta-analysis for Canada alone and also including the US data.
What did the study find?
  • The study cohorts included over one million patients with more than 80,000 keratinocyte carcinoma cases and close to 6,000 melanoma cases.
  • While HCTZ was not associated with an overall increased risk of keratinocyte carcinoma when compared with ACEIs (HR 1.02, 95% CI 0.98-1.07) or CCBs (HR 1.08, 95% CI 0.99-1.17), higher risks were observed with long-term use and higher cumulative doses. For melanoma, there was no clear evidence of an association when compared with ACEIs (HR 1.14, 95% CI 0.99-1.31) or by duration of use or dose.
  • When compared with CCBs, HCTZ was associated with a 32% increase in the risk of melanoma (HR 1.32, 95% CI 1.19-1.46), with higher risks observed with long-term use (≥10 years) and higher cumulative doses (≥100,000 mg).
  • Results were consistent when including the US data.
  • Strengths of the study include its large population size and long duration of follow-up. A limitation is the potential for confounding due to unmeasured factors (e.g., sun exposure, race, smoking).
Implications
  • These findings need to be considered in light of previous observational studies which highlighted increased risk of skin cancer; most of these studies were without active comparators, which increases the potential for confounding bias.
  • Given the importance of HCTZ in treating hypertension, physicians, patients, and decision-makers must weigh the benefits and risks of HCTZ compared with other antihypertensive drugs (e.g., ACEIs, CCBs).
Key message
  • The use of HCTZ was not associated with increased overall risks of keratinocyte carcinoma or melanoma when compared with ACEIs.
  • However, elevated risks of keratinocyte carcinoma and melanoma were observed with longer durations of use (≥10 years) and higher cumulative doses (≥100,000 mg) of HCTZ, particularly when compared with calcium channel blockers (CCBs).

Manuscripts

Azoulay L, St-Jean A, Dahl M, Quail J, Aibibula W, Brophy JM, Chan AW, Bresee L, Carney G, Eltonsy S, Tamim H, Paterson JM, Platt RW, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study. J Am Acad Dermatol. 2023;89(2):243-253.

Presentations

Project Team

Project Lead
Laurent Azoulay PhD
Methods Lead
Robert W. Platt PhD
Content Expert
James Brophy MD, PhD
Steering Committee Liaison
Michael Paterson MSc
Lead Analyst
Matthew Dahl BSc
Staff Scientist
Wusiman Aibibula PhD
Research Assistant
Audray St-Jean MSc
Site Investigator
Jacqueline Quail PhD
Saskatchewan
Site Investigator
Jacques LeLorier MD, MSc, FRCPC, FISPE
Quebec
Site Investigator
Michael Paterson MSc
Ontario
Site Investigator
Hala Tamim PhD
Atlantic
Site Investigator
Laura Dysart Postdoc Fellow
Atlantic
Site Investigator
Greg Carney BSc, PhD
MarketScan
Site Investigator
Sherif Eltonsy MSc, PhD
Manitoba
Site Investigator
Greg Carney BSc, PhD
British Columbia
Site Investigator
Lauren Bresee PhD
Alberta
Analyst
Shan Jin MSc
Saskatchewan
Analyst
Anjie Huang
Ontario
Analyst
David Stock PhD
Atlantic
Analyst
Yan Wang MSc
Atlantic
Analyst
Jason Kim MPH, BHSc
MarketScan
Analyst
Matthew Dahl BSc
Manitoba
Analyst
Nicole Croteau P.Stat
British Columbia
Analyst
Jianguo (James) Zhang MSc
Alberta