Aernoud Fiolet

305 Predictors of early intolerance to low-dose colchicine in patients with coronary disease reported for beta-blockers (estimated 3 to 5% in patients with heart failure) or aspirin (0.6 to 2.5% in the general population, 4.3-11% in adults with asthma, up to 6.6% in atherosclerosis). 17–20 The common occurrence of gastro-intestinal upset seems to be caused by epithelial injury due to a loss of cellular renewal and selective depression of intestinal enzyme activity following the anti-mitotic characteristics of colchicine. 21 Gastro- intestinal upset to colchicine is seen in most groups of patients and seems to be dose-dependent. The increased odds for intolerance of low-dose colchicine in females that we found has not been reported before and was not explained by other available demographical factors, medical history or by concomitant drug use. Sex-related increased risk for adverse drugs reactions have been described before. Various pharmacokinetic and pharmacodynamic factors and sex-related differences in concomitantly used drugs are postulated as biological explanation. 22 Sex-related differences in body fat percentage for example contribute to differences in absorption, distribution, metabolism and elimination of drugs. This has not yet been described for colchicine in particular. 23 This concept is however confirmed by our observation that obesity independently is associated with lower odds for intolerance. Following this rationale, the higher body fat percentage in females would be expected to lead to lower odds for intolerance in females as compared to males, contrary to our findings. Our data showing higher odds for intolerance in females may thus represent a behavourial mechanism. From a socio-cultural perspective, there are suggestions that female patients may perceive risks for trial participation different. 24 The reporting of intolerance due to any perceived side effect thus may also be driven by subconscious factors. The distribution of symptoms between sexes was essentially similar, although fatigue was reported more often by female patients. Hence, based on our data, we were not able to explain the sex related increased odds for intolerance. Contrary to our expectation, patients using high dose statins had lower odds of intolerance.We hypothesize that this probably reflects pre‑selection of patients less sensitive to statin-related side effects (most often myalgia) or patients less common to report side effects, rather than a biological etiology. It could be plausible that such a “survivor effect”- referring to those who survived the occurrence of side effects of earlier introduced drugs – also explains the inverse relation of ezetemibe use and intolerance.