Clopidogrel used on its own or in combination with low-dose aspirin may have a protective effect on colorectal cancer (CRC), a magnitude similar to that of low-dose aspirin alone, according to study results published in Clinical Gastroenterology and Hepatology.

Low-dose aspirin is shown to have a protective effect against CRC, perhaps on its ability to inactivate cyclooxygenase-1. However, it is currently unknown whether antiplatelet drugs with a different mechanism of action such as clopidogrel have the same protective effects. The objective of this study was to test whether clopidogrel has a similar chemoprotective effect on CRC compared with low-dose aspirin.

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In this case-control study, researchers collected data on 15,491 incident CRC cases and 60,000 randomly selected controls using the Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria database in Spain. Data was observed between January 1, 2001, and December 31, 2014, and included patients between the ages of 20 and 89. The effects of 3 antiplatelet drugs were studied: low-dose aspirin, clopidogrel, and triflusal. Researchers built multiple logistic regression models and computed adjusted-odds ratios (aORs) to estimate the association between exposure to different antiplatelet drugs and the risk for CRC.


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Results demonstrated that low-dose aspirin was associated with a reduced risk for CRC overall (aOR, 0.83; 95% CI, 0.78-0.89), and a reduced risk after more than 1 year of therapy (aOR, 0.79; 95% CI, 0.73-0.85) — the effect of which disappeared following discontinuation of therapy. The reduced risk began to be statistically significant after 180 days of therapy. Use of clopidogrel was also associated with a reduced risk for CRC overall (aOR, 0.80; 95% CI, 0.69-0.93), and a reduced risk after more than 1 year of therapy (aOR, 0.65; 95% CI, 0.55-0.78). 

Dual antiplatelet therapy with low-dose aspirin and clopidogrel was shown to have the same effect as either drug taken by itself.  No modification by sex or age was observed. Researchers observed a nonsignificant aOR among users of triflusal (aOR, 0.92; 95% CI, 0.76-1.12), and a trend of risk reduction among users of triflusal who received daily doses between 600 mg and 900 mg (aOR, 0.83; 95% CI, 0.62-1.11), which was more pronounced after more than 1 year of therapy (aOR, 0.75; 95% CI, 0.53-1.06).

This study had several limitations. First, there is a small probability of false-positive results that may have resulted in a minor dilution of the effect of the drugs used in this study. Second, misclassification of low-dose aspirin may be present in this study because aspirin can be dispensed over the counter and is nearly free in Spain, and commonly used long-term by those who also use other prescription cardiovascular drugs. Third, researchers were unable to analyze results based on antecedents of colonoscopy because tests were not recorded in a systematic way in the database. Lastly, due to the observational nature of this study, researchers could not rule out the possibility of unknown residual confounding.

The study researchers concluded that clopidogrel has a protective effect on CRC comparable to that of low-dose aspirin, which contributes to the concept that platelet targeting may be a promising strategy for disease prevention.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Rodríguez-Miguel A, García-Rodríguez LA, Gil M, Montoya H, Rodríguez-Martín S, de Abajo FJ. Clopidogrel and low-dose aspirin, alone or together, reduce risk of colorectal cancer. Clin Gastroenterol Hepatol. 2019;17(10):2024-2033.