Study links popular hypertension drug to increased skin cancer risk

Anastasia Tsirtsakis

5/08/2020 3:44:54 PM

But experts have warned against abruptly stopping their medication as a result.

Patient getting blood pressure tested.
Hypertension affects more than one third of Australians over the age of 18.

The drug in questions is hydrochlorothiazide, one of Australia’s most prescribed high blood pressure medications.
The new study, conducted by University of New South Wales (UNSW) scientists and published in Basic & Clinical Pharmacology & Toxicology, found an association between use of the drug and an increased risk of developing lip cancer and malignant melanoma for older Australians.
The drug contains photosynthesising properties, which can make skin more sensitive to the sun.
The findings are based on data provided by the Department of Veterans’ Affairs (DVA), for veterans aged 65 and over who lived in NSW between 2004 and 2015. It included de-identified information about GP visits and tests, medicine dispensing, hospitalisations, and cancer registrations. 
Researchers compared hydrochlorothiazide use in people who had been diagnosed with lip cancer (45 cases) or malignant melanoma (659 cases) with those who had neither diagnosis (13,300 controls).
‘We had an odds ratio for lip cancer of 2.6, so patients who were using hydrochlorothiazide were more than twice as likely to develop lip cancer than those who weren’t,’ Dr Benjamin Daniels, lead author of the study, told newsGP.
‘For cutaneous melanoma, the odds ratio was 1.2.
‘So that means there’s about a 20% increase in risk, or increase in the likelihood, of developing melanoma.
‘For lip cancer, the risk also appears to be cumulative – that is, the longer that hydrochlorothiazide is used, the higher the risk of developing lip cancer.’
Australia has one of the highest rates of skin cancer in the world, with around two in three people diagnosed by the age of 70. Hypertension affects more than one third of Australians over the age of 18.
Given these statistics, Dr Daniels, a pharmacoepidemiologist, says the findings of the new study are significant.
‘It’s obviously important for Australians, as there’s already a high baseline risk of developing various skin cancers in Australia,’ he said.
In response to the findings, the Therapeutic Goods Administration (TGA) has revised the product information for medicines containing hydrochlorothiazide to help GPs and other prescribers, as well as patients, make informed choices about the benefits and risks associated with taking the drug.
‘The results of this study confirm that the risk of skin cancer seen in international studies is relevant to Australians using medicines that contain hydrochlorothiazide,’ a TGA spokesperson said.
While Dr Daniels acknowledges the study’s findings may evoke fear, he cautions against patients abruptly stopping their medication.
‘It’s definitely a bit scary when you hear a medicine is associated with cancer,’ he said. ‘I think one’s instinct is probably to stop taking that medicine.
‘[But] hypertension is a condition that needs to be carefully managed. We don’t want anyone to suddenly stop taking hydrochlorothiazide out of fear of developing skin cancer.
‘The outcomes would probably be a lot worse if people stopped taking their hypertension control medicines, because that can lead to various serious consequences.’
Professor Mark Nelson, Research Fellow and Chair of General Practice at the University of Tasmania, is a Clinical Liaison of the High Blood Pressure Research Council of Australia.
He told newsGP the findings are ‘plausible from prior studies and supported by dosing effect for lip cancers’.
‘But effects [are] modest, [it is a] small sample size, and subject to residual confounding,’ he said.
‘Case-control design matched for age, so possibly could be associated with a survival advantage.
‘Melanoma with larger numbers, showed little effect.’
Professor Nelson said GPs would need to assess the risk for individual patients.
‘This study was conducted in an aged population where cardiovascular disease event risk is high and hydrochlorothiazide is a cheap and effective blood-pressure-lowering agent which reduces said risk,’ he said.
‘Therefore wholesale cessation is unwarranted.
‘Should GPs consider the adverse risk is relevant to their patient, then dose equivalent swapping to another diuretic agent would be justified.
‘It should also be a consideration in initiating an agent for blood pressure control.’
Dr Daniels said it is important that GPs and other prescribers are aware of associated skin cancer risks, and that the emphasis should be on ‘management and surveillance’.  
‘While there is risk, this risk is manageable,’ he reassured.
‘It’s something GPs and other prescribers should be aware of.
‘They might want to encourage sun-safe behaviours in their patients who are taking these medicines, [and] they might do more frequent skin checks. Because if these conditions do develop, they too are very manageable when they’re caught early on.’
While the dataset used was localised to an older population group, the results support findings from international studies that found similar risk estimates for all ages, said Dr Daniels.
‘Hydrochlorothiazide is used predominantly in older patients, as they tend to have high blood pressure more so than younger patients. But it’s absolutely worth exploring in a younger group,’ he said.
‘We hope to explore that if we can get our hands on some other data in younger Australians.’
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