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Clinical experience with ezetimibe/simvastatin in a Mediterranean population The SETTLE Study I. Migdalisa, A. Efthimiadisb, St. Pappasc, D. Alexopoulosd , F. Vlasseroue and D. P. Mikhailidisf a2nd Department of Internal Medicine, NIMTS General Hospital, Athens, Greece bCardiology Department, Hippokration General Hospital, Thessaloniki, Greece c3rd Department of Internal Medicine, NIKAIA General Hospital, Athens, Greece dCardiology Department, University Hospital of Rion, Patras, Athens, Greece eMedical Department, VIANEX Pharmaceuticals SA, Athens, Greece fDepartment of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free Campus, University College SETTLE Study Simvastatin Ezetimibe Therapy to Target Lipids Elevation Background Elevated plasma low-density lipoprotein cholesterol (LDL-C) is a pivotal risk factor in the development of atherosclerotic coronary heart disease (CHD). Optimal management of plasma LDL-C levels is the primary goal of therapeutic intervention in patients at risk of coronary events. 2 SETTLE Study Objective In hypercholesterolemic patients with LDL-C out of goal, despite prior use of statin monotherapy, to evaluate the efficacy of switching to ezetimibe/ simvastatin (EZE/SIMVA) 10/20 mg or 10/40 mg. To record CHD risk factors of hypercholesterolemic patients in Greece and observe the routine clinical practice of the use of ezetimibe / simvastatin 3 SETTLE Study: Patients The study was conducted at 100 sites all over Greece and included 1514 patients. male Male or female mean age: 60 yrs. female 46.6% 53.4% LDL-C out of goal, according to physician’s evaluation at screening visit All patients were previously treated with statin monotherapy 4 SETTLE Study: Patients The number of patients who had three risk factors or at least one CHD equivalent medical condition was 889 (58%) PATIENTS CO-MORBIDITIES / RISK FACTORS Diabetes Mellitus Hypertension Obesity Angina Myocardial infarction Revascularization procedure Stroke or peripheral arteriopathy Congestive heart failure Smoking Ex-smoking % 29.9% 61.2% 25.6% 10.5% 12.4% 14.1% 6.8% 2.9% 31.1% 15.7% 5 SETTLE Study: Efficacy Endpoints Primary % patients achieving LDL-C at study endpoint (post therapy, Visit 2) Secondary Mean % change in LDL-C, TC, TG, HDL-C at study endpoint (post therapy) Tolerability (monitoring of adverse experiences) 6 SETTLE Study: Study Design This was a Phase IV, multi-center, observational study Patients prior statin monotherapy: Simvastatin 20 or 40 mg Atorvastatin 10 or 20 mg Pravastatin 40 mg Fluvastatin 80 mg Rosuvastatin 5 mg Screening Week 0 Eze/Simva 10/20 mg/day (n=1074) Eze/Simva 10/40 mg/day (n=440) Week 8 No Washout Visit 1 Visit 2 7 SETTLE Study: Efficacy Parameters at Study Endpoint Changes in Lipid variables during the study Efficacy Parameter VISIT 1 VISIT 2 (mg/dl) Baseline Mean (± sd) Baseline Mean (± sd) LDL-C 164 (31) TC MEAN CHANGE (%) p-Value 107 (24) -33 <0.0001 248 (37) 182 (29) -26 <0.0001 45 (11) 48 (10) 10 NS TG† 174 (80) 137 (49) -15 0.021 non-HDL-C 203 (38) 134 (29) -32 <0.0001 HDL-C 8 SETTLE Study: Efficacy Parameters at Study Endpoint Changes in Lipid variables during the study (mean of absolute values, mg/dl) 300 56.8 mg/dl 250 37.1 mg/dl 66.7 mg/dl 200 150 3 mg/dl 100 50 0 TC LDL-C TG HDL-C 9 SETTLE Study: % of Patients Reaching LDL-C Goals at Study Endpoint At Goal Not at Goal 26.2% (n=397) (n=1117) 73.8% 10 Adverse experiences In 18 patients, 23 adverse experiences were reported (1.2%) Most of them were mild and expected (dizziness, rash, myalgia, GI symptoms, CPK increase in 2 patients, aminotransferase increase in 3 patients) There was one serious AE, which was NOT related to the study treatment. There was no difference in patients, at or NOT at goal. There was statistical difference in patients administered INEGY 10/20 or 10/40 mg There was no difference in patients more or less than 65 years old. 11 SETTLE Study: Summary of Results In patients taking a stable dose of statin monotherapy, switching to EZE/SIMVA 10/20 mg or 10/40 mg resulted in: Significantly greater reductions in LDL-C, TC, TG and non-HDLC, (p0.001) More patients achieving LDL-C goal, as this was determined by their attending physician (p0.001) In the routine clinical care setting, the safety/tolerability profile of EZE/SIMVA was favorable The present study showed that switching from statin monotherapy to EZE/SIMVA 10/20 mg or 10/40 mg provides greater reductions in LDL-C, resulting in clinically significant increases in the proportion of high-risk patients achieving LDL-C goals. 12 SETTLE Study: Conclusion In our Mediterranean population, the combination of EZE / SIMVA appears to be an appropriate and safe treatment option for patients who cannot achieve the LDL-C target with statin monotherapy 13