Antihypertensive drugs are prescribed to treat high blood pressure and are one of the most commonly prescribed drugs in the world. This group of drugs includes thiazide diuretics, which have been shown to be effective in reducing blood pressure. Recently, however, there have been some concerns that the use of thiazide diuretics may increase the risk of some cancers, including colorectal cancer. Thus, to address this concern, we will conduct a large study using the Clinical Practice Research Datalink to examine whether the use of thiazide diuretics is associated with an increased risk of colorectal cancer. Because colorectal cancer is the third most common cancer worldwide, results from this population-based study will provide important information on the long-term safety of these drugs.
Antihypertensive drugs are one of the most commonly prescribed drugs worldwide, with thiazide diuretics accounting for nearly 30% of these prescriptions. Recently, there have been controversies regarding the long-term safety of thiazide diuretics. Observational studies have reported associations with certain cancers, including colorectal cancer. To date, however, this possible association has been understudied and warrants further investigation. This is particularly important given that colorectal cancer has the third highest incidence among all cancers. To address this question, we will assemble a cohort of approximately 300,000 patients newly treated with either thiazides or dihydropyridine calcium channel blockers between January 1, 1988 and March 31, 2018, with follow-up until March 31, 2019. Cox proportional hazard models will be used to estimate hazard ratios with 95% confidence intervals of colorectal cancer comparing thiazide diuretics with dihydropyridine calcium channel blockers using standardized morbidity ratio weights. Secondary analyses will assess whether the risk of colorectal cancer varies by duration of use, cumulative dose, and by individual agents. To our knowledge, this will be the first study to specifically assess the association between thiazide diuretics and the incidence of colorectal cancer.
We all identify all incident colorectal cancer events occurring during the follow-up period recorded in either the CPRD (identified based on Read codes; see Table A1 in Appendix) or HES repository (based on ICD-10 codes; see Table A2 in Appendix). Diagnoses of colorectal cancer in the CPRD have been previously validated, with a positive predictive value of 98%, sensitivity of 92%, and specificity of 98%, when compared with diagnoses in the UK National Cancer Data Repository. Linkage with HES have resulted in further increases in sensitivity and specificity.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Emily McDonald - Collaborator - McGill University
Ilan Matok - Collaborator - The Hebrew University of Jerusalem
James Brophy - Collaborator - McGill University
Julie Rouette - Collaborator - McGill University
Laurent Azoulay - Collaborator - McGill University
Tibor Schuster - Collaborator - McGill University
Patient Level Index of Multiple Deprivation