Research Article Details

Article ID: A06856
PMID: 32720602
Source: Curr Vasc Pharmacol
Title: Have We Learnt all from IMPROVE-IT? Part I. Core Results and Subanalyses on the Effects of Ezetimibe Added to Statin Therapy Related to Age, Gender and Selected Chronic Diseases (Kidney Disease, Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease).
Abstract: IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized clinical trial (including 18,144 patients) that evaluated the efficacy of the combination of ezetimibe with simvastatin vs. simvastatin monotherapy in patients with acute coronary syndrome (ACS) and moderately increased low-density lipoprotein cholesterol (LDL-C) levels (of up to 2.6-3.2 mmol/L; 100-120 mg/dL). After 7 years of follow-up, combination therapy resulted in an additional LDL-C decrease [to 1.8 mmol/L, or 70 mg/dL, within the simvastatin (40 mg/day) monotherapy arm and to 1.4 mmol/L, or 53 mg/dL for simvastatin (40 mg/day) + ezetimibe (10 mg/day)] and showed an incremental clinical benefit [composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke; hazard ratio (HR) of 0.936, and 95% CI 0.887-0.996, p=0.016]. Therefore, for very high cardiovascular risk patients "even lower is even better" regarding LDL-C, independently of the LDL-C reducing strategy. These findings confirm ezetimibe as an option to treat very-high-risk patients who cannot achieve LDL-C targets with statin monotherapy. Additional analyses of the IMPROVE-IT (both prespecified and post-hoc) include specific very-high-risk subgroups of patients (those with previous acute events and/or coronary revascularization, older than 75 years, as well as patients with diabetes mellitus, chronic kidney disease or non-alcoholic fatty liver disease). The data from IMPROVE-IT also provide reassurance regarding longer-term safety and efficacy of the intensification of lipid-lowering therapy in very-high-risk patients resulting in very low LDL-C levels. We comment on the results of several (sub) analyses of IMPROVE-IT.
DOI: 10.2174/1570161118999200727224946

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I08 114 Cardiovascular system disease A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system disease of anatomical entity Details
I16 6713 Cerebrovascular disease An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease Details
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D248 Obeticholic Acid Chemical drug DB05990 NR1H4 activator; NR1H4 agonist; FXR agonist Enhance lipid metabolism Approval rejected Details
D131 Ezetimibe Chemical drug DB00973 SOAT1 inhibitor; Enhance lipid metabolism Under clinical trials Details