Bezafibrate & Ezetimibe in Dyslipidemia: J-COMPATIBLE Study
Bezafibrate & Ezetimibe in Dyslipidemia: J-COMPATIBLE Study
Low-density lipoprotein-cholesterol (LDL-C) is one of the most important factors for evaluating the risk associated with cardiovascular disorders. Statins are the most commonly used drug for treating elevated LDL-C, and reduce the risk of cardiovascular events, as demonstrated in large-scale clinical trials.
Although statin therapy reduces the risk of cardiovascular events by approximately 30%, the residual risk of cardiovascular events is approximately 70%. Therefore, it is necessary to consider additional interventions to reduce the residual risk. In addition to LDL-C, low levels of high-density lipoprotein-cholesterol (HDL-C) and high triglyceride (TG) concentrations are considered to be risk factors for coronary artery disease. For this reason, it is increasingly being acknowledged that integrated management of dyslipidemia targeting LDL-C as well as HDL-C and TG is necessary. In particular, the European Society of Cardiology/the European Atherosclerosis Society and the Japan Atherosclerosis Society recommend fibrates as the Class I pharmaceutical therapy for treating hypertriglyceridemia.
Fibrates activate peroxisome proliferator-activated receptor (PPAR) alpha, a nuclear receptor that affects the transcriptional regulation of many genes governing lipoprotein metabolism, thereby decreasing TG levels while increasing HDL-C levels. One of these drugs, bezafibrate, is a ligand for three PPAR subtypes (alpha, gamma, and delta) and exerts unique actions that differ from those of other fibrates. In contrast, ezetimibe is an inhibitor of Niemann-pick C1 like 1 protein (NPC1L1), an intestinal cholesterol transporter that is localized to the small intestinal mucosa. By inhibiting NPC1LI, ezetimibe reduces lipid uptake from the intestine, and thereby reduces hepatic cholesterol content and circulating LDL-C levels.
Because of these independent mechanisms of action, a combination of bezafibrate and ezetimibe is expected to provide a comprehensive treatment option for dyslipidemia by decreasing LDL-C, increasing HDL-C, and markedly decreasing TG levels. In fact, several studies have already documented the efficacy of fenofibrate in combination with ezetimibe. In contrast, a study combining bezafibrate and ezetimibe has not yet been conducted. For this reason, we conducted a 12-month prospective observational study (J-COMPATIBLE study; Japanese safety and efficacy of long-term COMbination theraPy with bazafibrAte and ezeTImiBe in patients with dysLipidEmia study) the safety and efficacy of bezafibrate in combination with ezetimibe for the treatment of dyslipidemia.
Background
Low-density lipoprotein-cholesterol (LDL-C) is one of the most important factors for evaluating the risk associated with cardiovascular disorders. Statins are the most commonly used drug for treating elevated LDL-C, and reduce the risk of cardiovascular events, as demonstrated in large-scale clinical trials.
Although statin therapy reduces the risk of cardiovascular events by approximately 30%, the residual risk of cardiovascular events is approximately 70%. Therefore, it is necessary to consider additional interventions to reduce the residual risk. In addition to LDL-C, low levels of high-density lipoprotein-cholesterol (HDL-C) and high triglyceride (TG) concentrations are considered to be risk factors for coronary artery disease. For this reason, it is increasingly being acknowledged that integrated management of dyslipidemia targeting LDL-C as well as HDL-C and TG is necessary. In particular, the European Society of Cardiology/the European Atherosclerosis Society and the Japan Atherosclerosis Society recommend fibrates as the Class I pharmaceutical therapy for treating hypertriglyceridemia.
Fibrates activate peroxisome proliferator-activated receptor (PPAR) alpha, a nuclear receptor that affects the transcriptional regulation of many genes governing lipoprotein metabolism, thereby decreasing TG levels while increasing HDL-C levels. One of these drugs, bezafibrate, is a ligand for three PPAR subtypes (alpha, gamma, and delta) and exerts unique actions that differ from those of other fibrates. In contrast, ezetimibe is an inhibitor of Niemann-pick C1 like 1 protein (NPC1L1), an intestinal cholesterol transporter that is localized to the small intestinal mucosa. By inhibiting NPC1LI, ezetimibe reduces lipid uptake from the intestine, and thereby reduces hepatic cholesterol content and circulating LDL-C levels.
Because of these independent mechanisms of action, a combination of bezafibrate and ezetimibe is expected to provide a comprehensive treatment option for dyslipidemia by decreasing LDL-C, increasing HDL-C, and markedly decreasing TG levels. In fact, several studies have already documented the efficacy of fenofibrate in combination with ezetimibe. In contrast, a study combining bezafibrate and ezetimibe has not yet been conducted. For this reason, we conducted a 12-month prospective observational study (J-COMPATIBLE study; Japanese safety and efficacy of long-term COMbination theraPy with bazafibrAte and ezeTImiBe in patients with dysLipidEmia study) the safety and efficacy of bezafibrate in combination with ezetimibe for the treatment of dyslipidemia.
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