George Lazaros
Cardiologist, Director of NHS,
1st University Cardiology Clinic
Hippocrateion General Hospital of Athens
Inflammation according to modern beliefs seems to play an important role in the atherosclerotic process. As shown in the CANTOS study in which 10,061 patients with a history of myocardial infarction and high sensitivity in C-reactive protein were randomized -hsCRP- ≥ 2mg / L or inhibition of pro-inflammatory cytokine interleukin 1b canakinunab plus 50- 300 mg in a monitoring period of 3,7 years, with 15% decrease of cardiovascular events compared with placebo, at the cost of a slight increase in fatal infections. Despite the positive outcome, canakinumab was not approved for cardiovascular prevention, possibly due to its high cost. In contrast, methotrexate, at a 15mg dose, did not show in a 2.3 years follow-up any reduction in cardiovascular events or a decrease in serum inflammatory markers versus placebo in the CIRT study, in which 4,786 patients with a history of myocardial infarction were randomized when in addition, they had either a previous myocardial infarction or a metabolic syndrome.
Given the conflicting results of these two major studies, the results of a recent COLCOT research study published in November 2019 in the New England Journal of Medicine (Jean-Claude Tardifetal. November 16, 2019, atNEJM.org. DOI: 10.1056 / NEJMoa1912388 ) were of particular interest. This study evaluated the safety and efficacy of colchicine in patients with recent myocardial infarction. Colchicine is a drug with known anti-inflammatory action that has been used for decades in the treatment of gout and more recently in the treatment of familial Mediterranean fever and pericarditis. Colchicine acts by inhibiting microtubule polymerization by binding to tubulin, one of the major constituents of cellular microtubules. The availability of tubulin is essential for cell mitosis. The COLCOT study included 4,745 patients with a history of myocardial infarction in the previous 30 days. The study was double-blind and the protocol provided for administration of colchicine (2366 patients (0.56 mg) or placebo (2,379 patients)). The primary endpoint at a follow-up of 22.6 months was the complex of cardiovascular death, recurrent cardiac death, myocardial infarction, stroke, urgent admission for angina for which angina was required. The above events were also checked individually as well as the safety profile of the drug.
According to the published data, the primary endpoint was reported in 5.5% of patients in the colchicine group and in 7.1% of the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; p = 0.02). . Risk factors (hazard ratios) were for cardiovascular death 0.84 (95% CI, 0.46 to 1.52), for recurrent heart death 0.83 (95% CI, 0.25 to 2.73), for myocardial infarction 0.91 (95% CI, 0.68 to 1.21), for stroke 0.26 (95% CI, 0.10 to 0.70) and for angina requiring urgent revascularization 0.50 (95% CI, 0.31 to 0.81). The overall impact of the primary efficacy endpoint is presented in the following figure:
Regarding the safety profile, diarrhea, the most common side effect of colchicine, was reported in 9.7% of patients on colchicine and in 8.9% of placebo patients (p = 0.35). Pneumonia was also reported as a significant side effect in 0.9% and 0.4% of patients on colchicine and placebo, respectively (p = 0.03).
In conclusion, according to the results of the COLCOT study in patients with recent myocardial infarction, the administration of colchicine at a dose of 0.5mg daily in addition to the gold standard medication recommended by the guidelines results in a statistically significant reduction in ischemic heart disease. The results of the COLCOT study are particularly important from a mechanistic point of view because they confirm the adverse effect of the inflammatory process on coronary heart disease but mainly, at the clinical level, to demonstrate the beneficial effect of colchicine, a cheap and time-tested drug, to the prognosis of patients with a recent myocardial infarction.
https://www.hcs.gr/default.aspx?pageid=1020
25/11/19
