CMAJ : Canadian Medical Association Journal
CMA Joule Inc.
image
Association between thiazide diuretics and skin cancer: still nebulous
DOI 10.1503/cmaj.78925 , Volume: 193 , Issue: 25 , Pages: E963-E963
Article Type: letter, Article History

Table of Contents

Highlights

Notes

I read with interest the article by Drucker and colleagues,1 which concludes, “higher cumulative exposure to thiazides was associated with increased risk of skin cancer.” No doubt an important study, and I agree that efforts should be made in identifying modifiable risk factors to prevent this. However, Table S7 in the supplementary appendix of the article shows that the hazard ratios for all 3 types of skin cancers were similar or higher with angiotensin receptor blockers when compared with thiazides (keratinocyte carcinoma: 1.09 v. 1.08; advanced keratinocyte carcinoma: 1.49 v. 1.07; and melanoma: 1.73 v. 1.34: angiotensin receptor blockers v. thiazide diuretics),1 yet the association between thiazides is highlighted in the manuscript. This association between thiazide diuretics and skin cancer was raised in some studies2,3 and refuted46 in others, and the study by Drucker and colleagues does not resolve this issue conclusively. Although the Pottegård study published in 20173 showed an association with lip cancer, another study by the same authors 2 years later4 failed to demonstrate or confirm this association. In fact, both hypertension and all antihypertensive agents are associated with increased risk of cancer, and 2 meta-analyses of observational studies failed to show evidence of association with the use of thiazide diuretics, but did show an association between calcium channel blockers and β-blockers.5,6 Furthermore, although diuretics were first-line agents in the treatment of hypertension, they have not held this status for uncomplicated hypertension for at least 2 decades,7 and any of the classes of antihypertensive agents, except β-blockers, may be used as first-line therapy. 7 The use of thiazides for treatment of hypertension has been declining,810 defined daily dose of thiazide diuretics is decreasing,11 and prescriptions for thiazides failed to increase despite the distribution of printed educational materials to primary care providers in Ontario.12 The effective control of blood pressure often requires multiple agents,13 increasing the cost and number of agents, and strategies to contain cost and number of pills should be considered.10

Since the publication of this article, the media have exaggerated this association in the population, and to clarify this issue, Hypertension Canada a week later posted a statement14 that such observational studies generate hypotheses and cannot provide proof of causality, and hypertension itself is associated with cancer risk. The organization advised the public that those who are concerned about this hypothetical risk should speak with their physician and, more importantly, should use measures to prevent skin cancer. Thiazides are important agents in controlling blood pressure and in reducing risk of death, stroke, heart failure and heart attack, and should not be stopped or withheld without assessing the risk–benefit ratio.

The incidence of skin cancer increased by 10% between 2005 and 2015, and focus should be on factors responsible for this increase in risk, rather than creating anxiety in the population about an important, cost-effective therapy for control of hypertension whose utilization is already decreasing worldwide.10,11

Competing interests:: None declared.

References

Drucker   AM , Hollestein   L , Na   Y , . Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study. CMAJ 2021;193:E50816.

Pedersen   SA , Gaist   D , Schmidt   SAJ , . Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018;78:673681.

Pottegård   A , Hallas   J , Olesen   M , . Hydrochlorothiazide use is strongly associated with risk of lip cancer. J Intern Med 2017;282:32231.

Pottegård   A , Pedersen   SA , Schmidt   SAJ , . Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study. Br J Cancer 2019;121:9738.

Tang   H , Fu   S , Zhai   S , . Use of antihypertensive drugs and risk of keratinocyte carcinoma: a meta-analysis of observational studies. Pharmacoepidemiol Drug Saf 2018;27:27988.

Gandini   S , Palli   D , Spadola   G , . Antihypertensive drugs and skin cancer risk: a review of the literature and meta-analysis. Crit Rev Oncol Hematol 2018;122:19.

Feldman   RD . The 1999 Canadian recommendations for the management of hypertension. On behalf of the Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension. Can J Cardiol 1999;15 Suppl G:57G64G.

Walker   RL , Chen   G , Campbell   NR , . Canadian provincial trends in antihypertensive drug prescriptions between 1996 and 2006. Can J Cardiol 2011;27:4617.

Moser   M , Feig   PU . Fifty years of thiazide diuretic therapy for hypertension. Arch Intern Med 2009;169:18516.

10 

Quinn   AE , Ronksley   PE , Bresee   L , . Antihypertensive prescribing for uncomplicated, incident hypertension: Opportunities for cost savings. CJC Open 2021 Jan. 19 [Epub ahead of print]. doi: 10.1016/j.cjco.2020.12.026

11 

McNally   RJ , Morselli   F , Farukh   B , . A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective. Br J Clin Pharmacol 2019; 85:270713.

12 

Zwarenstein   M , Grimshaw   JM , Presseau   J , . Printed educational messages fail to increase use of thiazides as first-line medication for hypertension in primary care: a cluster randomized controlled trial [ISRCTN72772651]. Implement Sci 2016;11:124.

13 

Derington   CG , King   JB , Herrick   JS , . Trends in Antihypertensive Medication Monotherapy and Combination Use Among US Adults, National Health and Nutrition Examination Survey 2005–2016. Hypertension 2020;75:97381.

14 

Campbell   N , Bell   A , Gros   R , . Statement on thiazide diuretics and skin cancer. Edmonton: Hypertension Canada; 2021. Available: hypertension.ca/wp-content/uploads/2021/04/HC-thiaz-skin-cancer-HCP-final-19-04-2021-1.pdf ( accessed 2021 Apr. 24 )
https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
https://www.researchpad.co/tools/openurl?pubtype=article&doi=10.1503/cmaj.78925&title=Association between thiazide diuretics and skin cancer: still nebulous&author=&keyword=&subject=Letters,