De invloed van colchicine op de bloedstolling bij patiënten met chronische coronaire aandoeningen die vitamine-K antagonisten gebruiken

Abstract

The effect of colchicine on coagulation in patients using vitamin K antagonists with chronic coronary disease Background Low-dose colchicine (0.5 mg/day) improves cardiovascular outcomes in patients with coronary disease. Around 12% of these patients simultaneously use anticoagulant therapy. In vitro studies and case reports describe a possible drug interaction between colchicine and vitamin K antagonists (VKAs). Objective The aim of this study was to investigate if there is a clinically relevant drug interaction between colchicine and VKAs in patients with chronic coronary disease. Design and methods This study was a sub-analysis of the randomized Low-Dose Colchicine 2 (LoDoCo2) trial in which colchicine 0.5 mg once daily was compared with placebo in patients with chronic coronary disease. For the current study we included a sample of patients who used a VKA. All patients were subject to a one month open-label run-in phase in which they received colchicine 0.5 mg once daily. The primary outcome was the within-patient difference in International Normalised Ratio (INR) after starting or stopping colchicine as compared to one month before. Secondary outcomes were difference in mean daily dosage of VKAs and Time in Therapeutic Range [I IK). Results In total, 73 patients were included (35 in colchicine group and 38 in placebo group). No difference in mean INR was found after the introduction of colchicine (0.07; 95% confidence interval [Cl]: -0.13-0.26; P = 0.50) or when stopping (0.11; 95% Cl: -0.12-0.33; P = 0.34). The change in mean VKA daily dosage was -0.01 mg (95% Cl: -0.033-0.012; P = 0.35) when starting colchicine and -0.01 mg (95% Cl: -0.029-0.012; P = 0.41) when stopping colchicine. The change in TTR one year prior to the study compared to one year after randomization to colchicine was 7.56% (95% Cl: -0.14-15.3; P = 0.054). Conclusion We found no clinically relevant difference in mean INR in patients using VKAs after starting, using or stopping colchicine. These results suggest that low-dose colchicine can be used safely in patients treated with VKAs, without the need for INR monitoring other than the standard of care.