Inflammation in Cardiovascular Disease: From Basic Concepts to Clinical Application

Abstract Although low-density lipoprotein cholesterol is central to the development and progression of atherosclerosis, the role of inflammation in the atherosclerotic process is becoming better understood and appreciated. Chronic inflammatory conditions such as rheumatoid arthritis, lupus, psoriasis, HIV infection, and inflammatory bowel disease have all been shown to be associated with an increased blood levels of inflammatory biomarkers and increased risk of cardiovascular events. Evidence from observational studies suggests that anti-inflammatory therapy decreases this risk in these conditions. Clinical trials of anti-inflammatory drugs in patients with coronary disease have yielded mixed results. Drugs that have failed in recent trials include the P38 MAP kinase inhibitor losmapimod, the phospholipase A2 inhibitors darapladib and varespladib, and methotrexate. Canakinumab, an interleukin-1β inhibitor, reduced cardiovascular events in patients with coronary disease in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS). Canakinumab increased the rate of fatal infections in CANTOS and is very expensive; it is thus unlikely to be widely used for risk reduction in cardiology. On the other hand, colchicine is a safe and inexpensive anti-inflammatory drug. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), where patients within 30 days of a myocardial infarction were randomized to low-dose colchicine or placebo and followed for a median of almost 2 years, colchicine treatment was associated with a 23% reduction (p=0.02) in cardiovascular events. Newer studies with anti-inflammatory drugs have the potential to improve outcomes of patients with atherosclerosis, just as low-density lipoprotein cholesterol-lowering drugs have done over the past two decades.

Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization / Colchicina para Redução de Fibrilação Atrial em Pós-Operatório de Revascularização Miocárdica

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Resumo Fundamento: A alta prevalência de fibrilação atrial (FA) no pós-operatório de cirurgia de revascularização miocárdica ocasiona maior morbidade e mortalidade. Objetivos: Avaliar a eficácia da colchicina como profilaxia para FA no pós-operatório de cirurgia de revascularização miocárdica, o impacto da FA sobre o tempo de internação hospitalar e óbito e identificar fatores de risco para o seu aparecimento. Métodos: Entre maio de 2012 e novembro de 2013, 140 pacientes submetidos à cirurgia de revascularização miocárdica foram randomizados, 69 no grupo controle e 71 no grupo colchicina. A colchicina foi utilizada na dose de 1 mg via oral, duas vezes ao dia, no pré-operatório, e 0,5 mg, duas vezes ao dia, até a alta hospitalar. Dose única de 1 mg foi administrada aos internados 12 horas ou menos antes da cirurgia. Resultados: O desfecho primário foi a taxa de FA no pós-operatório de cirurgia de revascularização miocárdica. Os pacientes do grupo colchicina não apresentaram redução na incidência de FA em comparação aos do grupo controle (7,0% versus 13,0%, respectivamente; p = 0,271). Não houve diferença estatisticamente significativa entre os grupos em relação à taxa de óbito por qualquer causa (5,6% versus 10,1%; p = 0,363) e ao tempo de internação (14,5 ± 11,5 versus 13,3 ± 9,4 dias; p = 0,490). Porém, o grupo colchicina apresentou maior taxa de infecção (26,8% versus 8,7%; p = 0,007). Conclusões: O uso da colchicina para profilaxia da FA no pós-operatório de revascularização miocárdica não se mostrou eficaz neste estudo. Registro Brasileiro de Ensaios Clínicos número RBR-556dhr.