Thiazides associated with increased risk for skin cancer in older adults
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Adults aged over 65 years who took thiazides for hypertension had an increased risk for keratinocyte carcinoma and melanoma, according to results of a population-based cohort study.
“It is important to think about the increased risk of skin cancer associated with thiazide diuretics in the context of the whole patient,” study co-author Aaron M. Drucker, MD, ScM, a dermatologist at Women’s College Hospital and an assistant professor at the University of Toronto, told Healio Primary Care. “While we couldn’t study this specifically in our study, the risk is probably most important for people already at higher risk for skin cancer, such as people with fair skin, a lot of existing sun damage or artificial tanning over time and people who have already had a skin cancer or precancer.”
Husam Abdel-Qadir MD, PhD, FRCPC, a cardiologist at the Women’s College Hospital and University Health Network and an assistant professor at the University of Toronto who was also involved in the study, said that thiazide diuretics are commonly used for hypertension because “they are effective, inexpensive and generally well tolerated.” However, previous reports have linked the agents to keratinocyte carcinoma and melanoma.
To verify these reports, Drucker, Abdel-Qadir and colleagues conducted a population-based inception cohort study of administrative health data from Ontario that was gathered from 1998 to 2017. The analysis included 302,634 adults aged over 65 years (mean age at index, 70 years; 63% women) who had a first prescription for thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers or beta-blockers. They were matched by age and sex with 605,268 adults (mean age at index, 70 years; women, 63%) who were not exposed to these medications. The study’s primary outcome measure was time to first keratinocyte carcinoma, advanced keratinocyte carcinoma or melanoma.
Increasing thiazide exposure correlated with an increased risk for incident keratinocyte carcinoma (adjusted HR [aHR] = 1.08; 95% CI, 1.03-1.14), advanced keratinocyte carcinoma (aHR = 1.07; 95% CI, 1.01-1.78) and melanoma (aHR = 1.34; 95% CI, 1.01-1.78), but there was “no consistent evidence between other anti-hypertensive classes and keratinocyte carcinoma or melanoma,” according to the researchers.
“I do not think the risk of skin cancer is well recognized; I did not know about it before this study,” Abdel-Qadir said.
Although future research could elucidate the risk for skin cancer among high-risk populations in more detail, Drucker and Abdel-Qadir said that there are steps providers can take to mitigate risk based on their findings.
“For patients with skin cancer risk factors, a primary care doctor could weigh the increased risk of skin cancer against the importance of thiazide diuretics to treat their hypertension,” Drucker said. “Are there alternatives that will be as effective and safe overall that can be used instead?”
Providers can also “emphasize the importance of sun protection and following recommendations about prevention of skin cancers,” Abdel-Qadir said.
Perspective
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There has been some suggestion in previous studies that a class of anti-hypertensive medicines for BP — thiazides — leads to increased rates of both nonmelanoma (squamous cell and basal cell carcinoma) and melanoma skin cancers. The hypothesis is that increased exposure to these medications due to phototoxicity can lead to changes and damage to the skin, leading to cancer formation. This study was conducted in Ontario. The researchers used administrative health data comparing approximately 300,000 patients exposed to different types of anti-hypertensive drugs, including thiazides, to a matched cohort of patients who were not exposed.
They found that increasing exposure to only the thiazide type of anti-hypertensive drugs led to an increased incidence of both nonmelanoma and melanoma skin cancers in patients over the age of 65. There was no increased risk in the use of other classes of anti-hypertensive medications.
This is a very interesting study, and although there are many limitations to these types of large population-matched cohort studies, the take-home point is that physicians should be aware of the use of thiazides in this patient population. Further research is warranted to confirm their findings. However, clinicians should consider altering their choice of anti-hypertensive medications, if possible, in patients over the age of 65, or be aware of the risk and make sure patients are educated on skin cancer awareness, screening with routine dermatologic examinations and sun exposure prophylaxis with sunscreen and sun protection strategies.
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