CO10 Clopidogrel shares with low‐dose acetylsalicylic acid a comparable protection against colorectal cancer: a population‐based case‐control study

Abstract

Objectives: The mechanism of action of low-dose acetylsalicylic acid (ASA) to explain its chemopreventive action on colorectal cancer (CRC) is still debated. Some evidence suggests that the antiplatelet effect of low-dose ASA (through irreversible inhibition of platelet-COX-1) might be the principal mechanism. This platelet hypothesis would be reinforced if other antiplatelet agents, acting through a mechanism of action unrelated to COX-1 as clopidogrel, would present a comparable effect to low-dose ASA.Methods: A case-control study nested in a primary cohort selected from the Spanish primary care database BIFAP between 2001 and 2014. Individuals aged 20-89 and without previous history of cancer were followed-up until an incident CRC record (index date), other cancer record, 90 years, death or end of study. 15 491 incident CRC cases were detected and validated and 60 000 controls were randomly selected (incidence-density sampling) and frequency matched to cases by age, sex and year of index date. Exposure was classified as current (0-90 days prior index date), recent (91-365), past (>365) and non-use. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were computed by logistic regression adjusted for potential confounders.Results: Current use of clopidogrel monotherapy presented a reduced risk of CRC; AOR = 0.80 (95% CI: 0.69-0.93) and 0.65 (0.55-0.78) after 1 year of treatment. This effect was maintained by age and sex. Current use of low-dose ASA was associated with an AOR of 0.83 (0.78-0.89) and0.79 (0.73-0.84) for periods longer than 1 year. Dual antiplatelet therapy presented a similar effect than the one observed among single users of each antiplatelet drug.Conclusions: The use of clopidogrel was associated with a risk reduction of CRC, duration-dependent and similar in magnitude to the one observed among users of low-dose ASA, giving support to the antiplatelet action as the main mechanism behind their chemopreventive effect on CRC.