ezetimibe--simvastatin-drug-combination and Diabetes-Mellitus

IMPROVE-IT study demonstrated that the addition 10 mg of ezetimibe to 40 mg of simvastatin in patients after acute coronary syndrome reduces significantly not only their LDL-cholesterol, but also the number of cardiovascular events. Recently published subanalysis of this study was focused on whether these combinations of drugs is more preferable for patients with diabetes mellitus or for patients without diabetes. The addition of ezetimibe to a simvastatin resulted in a greater decline of LDL-cholesterol level in diabetic group than in patients without diabetes. In patients with diabetes mellitus their cardiovascular morbidity and mortality were decreased significantly; reduction of these clinical end-points in the group of patients without diabetes were not statistically significant.

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, LDL; Diabetes Mellitus; Europe; Ezetimibe, Simvastatin Drug Combination; Humans; Incidence

Treatment guidelines identify low-density lipoprotein cholesterol (LDL-C) as the primary target of therapy with secondary targets of non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB). Data were pooled from 27 randomised, double-blind, active or placebo-controlled trials in 21,794 adult hypercholesterolaemic patients (LDL-C 1.81-6.48 mmol/L) receiving ezetimibe/statin or statin for 4-24 weeks. Percentages of patients achieving various targets were calculated among diabetes (n = 6541) and non-diabetes (n = 15,253) subgroups. Significantly more patients with and without diabetes achieved specified levels of LDL-C (< 2.59, < 1.99, < 1.81 mmol/L), non-HDL-C (< 3.37, < 2.59 mmol/L) and apoB (< 0.9, < 0.8 g/L) with ezetimibe/statin versus statin. Patients with diabetes had larger mean per cent reductions in LDL-C and non-HDL-C than non-diabetes patients. A greater percentage of patients achieved both the LDL-C and apoB targets and all three LDL-C, apoB, and non-HDL-C targets with ezetimibe/statin versus statin in both subgroups. Patients with diabetes benefitted at least as much as, and sometimes more than, non-diabetes patients following treatment with ezetimibe/statin.

Topics: Aged; Anticholesteremic Agents; Apolipoproteins B; Azetidines; Biomarkers; Cholesterol, LDL; Diabetes Mellitus; Drug Combinations; Evidence-Based Medicine; Ezetimibe, Simvastatin Drug Combination; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Simvastatin; Time Factors; Treatment Outcome; Triglycerides

Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known.. This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states.. Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline.. The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.

Topics: Aged; Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus; Drug Therapy, Combination; Ezetimibe, Simvastatin Drug Combination; Female; Glucose Intolerance; Humans; Hypolipidemic Agents; Insulin; Intention to Treat Analysis; Male; Middle Aged; Niacin

To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients.. This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks.. FG levels peaked by 8-12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification.. Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment.

Topics: Adolescent; Adult; Age of Onset; Aged; Azetidines; Delayed-Action Preparations; Diabetes Complications; Diabetes Mellitus; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Niacin; Simvastatin; Time Factors; Young Adult

Patients with diabetes mellitus (DM) and metabolic syndrome are at increased risk of coronary heart disease (CHD). Studies have shown differential statin efficacy on low-density lipid cholesterol (LDL-C) by CHD risk strata.. The aim of this study was to evaluate the consistency of effect with ezetimibe/simvastatin (E/S) combination therapy, atorvastatin, or rosuvastatin in patients with DM, metabolic syndrome, or neither condition (No DM/metabolic syndrome), stratified by the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) CHD risk group.. Post hoc analyses of 2 multicenter, double-blind, randomized, 6-week studies comparing E/S 10/10, 10/20, 10/40, or 10/80 mg with either atorvastatin 10, 20, 40, or 80 mg, or rosuvastatin 10, 20, or 40 mg. Treatments were compared by pooling across all doses for LDL-C reduction and NCEP LDL-C goal attainment in patients with DM, metabolic syndrome without DM, or No DM/metabolic syndrome across NCEP CHD risk strata.. NCEP LDL-C goal attainment was lowest in the high-risk group with atherosclerotic vascular disease (12-64%) and greatest in the moderate and low-risk groups (84-100%). In contrast, LDL-C reduction was generally similar irrespective of disease or risk subgroup. All treatments were generally well tolerated, with overall similar safety regardless of disease and risk level.. In these studies, CHD risk strata were inversely related to the likelihood of attaining NCEP LDL-C goals, but did not appear to affect the percentage LDL-C change from baseline. This demonstrates the need for especially aggressive cholesterol lowering necessary to reach the lower LDL-C goal for high-risk patients.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Azetidines; Cholesterol, LDL; Coronary Disease; Diabetes Mellitus; Double-Blind Method; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolic Syndrome; Middle Aged; Pyrimidines; Pyrroles; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Topics: Anticholesteremic Agents; Cholesterol, LDL; Diabetes Mellitus; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Clinical trials suggested that the benefits of ezetimibe-statin combination therapy on major adverse cardiovascular events (MACE) might be greater in patients with diabetes. We aimed to investigate the differential association of ezetimibe-statin combination with incident MACE by presence of diabetes. In this retrospective cohort study, subjects treated with simvastatin 20 mg plus ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) between 2005 and 2015 were 1:1 matched using propensity score as stratified by diabetes. Primary outcome was newly-developed MACE composed of cardiovascular death, ACS, coronary revascularization, or non-hemorrhagic stroke. During 5,077 and 12,439 person-years, the incidence rates of MACE were 24.9, 20.1, 35.3, and 22.8/1000 person-years among no diabetes S, no diabetes S + E, diabetes S, and diabetes S + E, respectively. Relative to no diabetes S, adjusted HR (aHR) for MACE in diabetes S was 1.23 (p = 0.086), whereas S + E was associated with a lower risk of MACE in both non-diabetic patients (aHR 0.76, p = 0.047) and diabetic patients (aHR 0.60, p = 0.007) with significant difference (relative excess risk due to interaction = -0.39, p = 0.044). In conclusion, reduction of MACE risk associated with ezetimibe plus simvastatin therapy relative to simvastatin alone was greater in patients with diabetes than in patients without diabetes.

Topics: Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Propensity Score; Retrospective Studies; Simvastatin; Treatment Outcome

Topics: Anticholesteremic Agents; Diabetes Mellitus; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Topics: Anticholesteremic Agents; Diabetes Mellitus; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors