Associations of Statin Use With Colorectal Cancer Recurrence and Mortality in a Danish Cohort

Abstract

In earlier studies of the influence of hydroxymethylglutaryl-coenzyme A reductase inhibitors (also known as statins) on colorectal cancer prognosis, investigators reported a reduced rate of cancer-specific mortality. Studies of recurrence are few and small. Using data from Danish registries, we followed 21,152 patients diagnosed with stage I-III colorectal cancer from 2001 to 2011. We estimated the association between statin use in the preceding year and cancer recurrence, cancer-specific mortality, and all-cause mortality rates. We identified 5,036 recurrences, 7,084 deaths from any cause, and 4,066 deaths from colorectal cancer. After adjustment for potential confounders, statin use was not associated with recurrence (adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.93, 1.09), but it was associated with death from colorectal cancer (aHR = 0.72, 95% CI: 0.65, 0.79) and death from any cause (aHR = 0.72, 95% CI: 0.67, 0.76). Statin use in the year preceding recurrence was associated with a reduced risk of cancer-specific mortality (aHR = 0.83, 95% CI: 0.74, 0.92) but also a reduced risk of death from any other cause (aHR = 0.78, 95% CI: 0.61, 1.00). Statin use was not associated with a reduced rate of colorectal cancer recurrence, but it was associated with a reduced rate of cancer-specific mortality, which suggests that there is no cancer-directed benefit; therefore, there is no basis to prescribe statins to colorectal cancer patients who do not have cardiovascular indications.

Statin uses and mortality in colorectal cancer patients: An updated systematic review and meta‐analysis

“…Detailed characteristics of the included studies were summarized in Table . Generally, six studies involving 86 622 patients reported survival outcomes for patients of pre‐diagnostic statin uses, while 11 studies involving 44 322 patients investigated survival outcomes related to post‐diagnostic statin uses . Eight studies were conducted in Europe (United Kingdom, Denmark, Netherland, Germany), four in North America, and two in Asia (China, Korea) .…”

“…Generally, six studies involving 86 622 patients reported survival outcomes for patients of pre‐diagnostic statin uses, while 11 studies involving 44 322 patients investigated survival outcomes related to post‐diagnostic statin uses . Eight studies were conducted in Europe (United Kingdom, Denmark, Netherland, Germany), four in North America, and two in Asia (China, Korea) . Six studies investigated patients with stages I‐IV, four with stages I‐III, two with stage III, one with stages II‐III, one with stage IV cancer .…”

Validating registry data on statins prescriptions by blood measurements

“…The "Stender cohort" included patients admitted for curative surgery 18 from October 2003 to November 2005. Patients were followed with clinical examination for signs of deep venous thrombosis at 1,3,6,9,12,18,24,30,36,48, and 60 months after surgery. The COLOFOL cohort included patients who had resection for colorectal cancer between January 2006 and January 2011 (clinicaltrials.gov identifier NCT00225641).…”

“…Apart from protection against cardiovascular conditions, statins affect immune function and may reduce risk of other diseases including cancer . Studies of these pleiotropic effects have often used routinely registered prescription data and are therefore dependent on data validity …”

“…5 Studies of these pleiotropic effects have often used routinely registered prescription data and are therefore dependent on data validity. [5][6][7] Prescription registries benefit from being readily available for large cohorts and independent of patient's recall but suffer from lack of information on adherence. Different approaches have been made to estimate adherence, for instance by calculating a medication possession ratio 8,9 or by comparing expected pill count to actual pill count midway through a prescription.…”