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C-REACTIVE PROTEIN (CRP) AND LDL-CHOLESTEROL RESPONSE TO EZETIMIBE MONOTHERAPY AND TO EZETIMIBE ADDED-ON TO BASELINE STATIN THERAPY
Poster Sessions PO44 Therapeutic interventions – ezetimibe Results: In the E/S + niacin and niacin groups, LDL-C (fig.), TG, non-HDL-C, and Total C improved with increasing doses of niacin during the 16 wk titration to the 2g dose, then were maintained through 24 wks. HDL-C (fig.) levels increased during the 16 wk titration and continued throughout 24 wks with both niacin treatments. Reductions in LDL-C and TG, and increase in HDL-C by E/S were constant during 4-24 wks. Conclusion: Improvements in LDL-C lowering and the lipid profile achieved by E/S + niacin treatment were related to the overall E/S effect and dose-dependent increases in niacin to 2g during 16 wks, which persisted through 24 wks. In addition, HDL-C levels continued to increase during 16 to 24 wks at the 2g niacin dose, in a time-related manner. E/S + niacin provides a broad lipid-altering option for treatment of HL patients. PO44-688
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was 17.2%, both p<0.001. Treatment by age subgroup interaction was not significant for both comparisons (p=0.372; p=0.401). Rates of any AEs were similar across subgroups for both comparisons. Significant CK elevations >10X upper limit of normal occurred in 0% of EZE/Statin and 0.1% of Statin subjects; persistent transaminase elevations occurred in 0.3% and 0.4% of subjects, respectively.
C-REACTIVE PROTEIN (CRP) AND LDL-CHOLESTEROL RESPONSE TO EZETIMIBE MONOTHERAPY AND TO EZETIMIBE ADDED-ON TO BASELINE STATIN THERAPY
T. Pearson 1 , C. Ballantyne 2 , E. Veltri 3 , A. Shah 4 , S. Bird 5 , J. Lin 4 , E. Rosenberg 5 , A. Tershakovec 5 . 1 University of Rochester, School of Medicine; 2 Baylor College of Medicine; 3 Schering-Plough; 4 Merck & Co., Inc., Rahway; 5 Merck & Co., Inc., North Wales
PO44-689
EFFICACY AND SAFETY OF EZETIMIBE AND EZETIMIBE+STATIN IN YOUNG AND ELDERLY PATIENT POPULATIONS
J. Robinson 1 , M. Davidson 2 , A. Shah 3 , J. Lin 3 , E. Veltri 5 , K. Lantz 3 , A. Tershakovec 3 , P. Brudi 4 . 1 University of Iowa, Iowa City, IA, USA; 2 Rush University School of Medicine, Chicago, IL, USA; 3 Merck & Co., Inc., West Point, PA, USA; 4 Merck Schering-Plough Cholesterol Partnership, Whitehouse Station, NJ, USA; 5 Schering-Plough Research Institute, Kenilworth, NJ, USA Background: Trials of lipid-lowering agents have enrolled general adult populations, resulting in limited data relating to the elderly. We evaluated LDL-C-lowering efficacy of ezetimibe (EZE) and EZE + any statin (EZE/Statin) across age subgroups (<65, 65-74, & ≥75 years) in pooled data of 16 studies ranging 6-12 weeks. Methods: Results of randomized, double-blind, placebo (PBO)controlled and comparator studies of EZE and/or EZE/Statin were analyzed using ANOVA on a modified intent-to-treat population for effects on LDL-C of EZE vs PBO and EZE/Statin vs any Statin. Results: % change from baseline in LDL-C for EZE vs PBO and for EZE/Statin vs Statin by age is presented. Difference in LDL-C reduction between EZE & PBO was 19.7% and between EZE/Statin & Statin
Conclusions: The efficacy and safety of EZE & EZE/Statin in the elderly is similar to that in non-elderly. These results have implications when selecting lipid-lowering agents in elderly patients. PO44-690
THE EFFECT OF SIMVASTATIN/EZETIMIBE ADMINISTRATION IN THE MANAGEMENT OF PRIMARY HYPERLIPIDEMIA
E. Paschalidou 1 , Ap. Efthimiadis 1 , I. Efthimiadis 1 , V. Milioni 1 , A. Zafeiris 1 , A. Tavridou 2 , M. Raptopoulou-Gigi 1 . 1 Atherosclerosis Outpatient Clinic, 2nd Department of Internal Medicine, Hippocration General Hospital, Medical School, Aristotle University of Thessaloniki, Greece; 2 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece Background and aims: Simvastatin is a potent HMG-CoA inhibitor and ezetimibe is a potent inhibitor of cholesterol absorption. The last 2 years these two agents are administered combined in one pill for the better management of hyperlipidemias. We sought to determine the effect of the above combination in the management of primary hyperlipidemia. Methods: 30 subjects (18 men and 12 women) aged 54.25±12.38 years, with untreated primary hyperlipidemia (total cholesterol: 295.8±50.76 mg/dl, LDL-C: 210.1±48.36mg/dl) without active coronary artery disease were followed. All subjects received simvastatin/ezetimibe 40/10 mg one pill/day for three months. Before and after treatment lipid profile, liver enzymes, creatinine and urea were determined by the standard methods. Paired t-test was used to compare means at baseline and after treatment. Data are presented as mean±standard deviation. Results: Administration of the combination simvastatin/ezetimibe 40/10 mg/day statistically improve the lipid profile: total cholesterol decreased by 32%, LDL-C decreased by 42.6%, p<0.0001, triglycerides decreased by 22.8% p<0.0001 and HDL-C increased by 9.8% p<0.1. Liver enzymes levels were inside normal range so as CPK levels and renal function was not influenced. Conclusions: Combination hypolipidemic therapy using the simvastatin/ezetimibe 40/10 mg/day scheme did statistically improve lipid profile achieving the target of LDL-C for primary prevention (<130mg/dl), without any influence in renal or liver function. During the treatment no adverse event was reported.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and Aims: Inflammation is central to coronary heart disease (CHD). Effects of ezetimibe as monotherapy or add-on to baseline statin-therapy on CRP, a marker of inflammation, and on LDL-C were examined. Methods: Results of randomized, placebo-controlled trials of ezetimibe 10mg in hypercholesterolemic adults were pooled in 2 analyses: six 12-week monotherapy trials (n=1372); seven 6-8 week add-on to baseline statin-therapy trials (n=3899). In patients with CRP<10mg/L, ANOVA was used to evaluate treatment effects on mean % changes from baseline in CRP and LDL-C. Spearman correlation coefficients among CRP and LDL-C levels at baseline and after treatment were calculated. Results: For both analyses, baseline characteristics were similar between groups. CRP reduction with ezetimibe monotherapy was numerically greater than placebo (treatment difference 6.0%, P=0.094), and with ezetimibe added to baseline statin-therapy was significantly greater than placebo (treatment difference 10.4%, P<0.001). Treatment effects were consistent across subgroups (age, gender, race, BMI, diabetes, metabolic syndrome, CHD, baseline CRP or lipids, and statin potency). In both analyses, LDL-C reduction with ezetimibe was significantly greater than placebo (P<0.001). Correlations were only significant, and weakly positive, between % changes from baseline in CRP and LDL-C when ezetimibe was added to baseline-statin-therapy. Conclusions: Although the effect of ezetimibe monotherapy on CRP was limited, when ezetimibe was added to baseline statin treatment, CRP reduction was enhanced. Correlations between CRP and LDL-C were weak or non-significant. Effects of ezetimibe on CRP were consistent across patient subgroups. The clinical relevance of changes in CRP to atherothrombotic risk needs further investigation.
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was 17.2%, both p<0.001. Treatment by age subgroup interaction was not significant for both comparisons (p=0.372; p=0.401). Rates of any AEs were similar across subgroups for both comparisons. Significant CK elevations >10X upper limit of normal occurred in 0% of EZE/Statin and 0.1% of Statin subjects; persistent transaminase elevations occurred in 0.3% and 0.4% of subjects, respectively.
C-REACTIVE PROTEIN (CRP) AND LDL-CHOLESTEROL RESPONSE TO EZETIMIBE MONOTHERAPY AND TO EZETIMIBE ADDED-ON TO BASELINE STATIN THERAPY
T. Pearson 1 , C. Ballantyne 2 , E. Veltri 3 , A. Shah 4 , S. Bird 5 , J. Lin 4 , E. Rosenberg 5 , A. Tershakovec 5 . 1 University of Rochester, School of Medicine; 2 Baylor College of Medicine; 3 Schering-Plough; 4 Merck & Co., Inc., Rahway; 5 Merck & Co., Inc., North Wales
PO44-689
EFFICACY AND SAFETY OF EZETIMIBE AND EZETIMIBE+STATIN IN YOUNG AND ELDERLY PATIENT POPULATIONS
J. Robinson 1 , M. Davidson 2 , A. Shah 3 , J. Lin 3 , E. Veltri 5 , K. Lantz 3 , A. Tershakovec 3 , P. Brudi 4 . 1 University of Iowa, Iowa City, IA, USA; 2 Rush University School of Medicine, Chicago, IL, USA; 3 Merck & Co., Inc., West Point, PA, USA; 4 Merck Schering-Plough Cholesterol Partnership, Whitehouse Station, NJ, USA; 5 Schering-Plough Research Institute, Kenilworth, NJ, USA Background: Trials of lipid-lowering agents have enrolled general adult populations, resulting in limited data relating to the elderly. We evaluated LDL-C-lowering efficacy of ezetimibe (EZE) and EZE + any statin (EZE/Statin) across age subgroups (<65, 65-74, & ≥75 years) in pooled data of 16 studies ranging 6-12 weeks. Methods: Results of randomized, double-blind, placebo (PBO)controlled and comparator studies of EZE and/or EZE/Statin were analyzed using ANOVA on a modified intent-to-treat population for effects on LDL-C of EZE vs PBO and EZE/Statin vs any Statin. Results: % change from baseline in LDL-C for EZE vs PBO and for EZE/Statin vs Statin by age is presented. Difference in LDL-C reduction between EZE & PBO was 19.7% and between EZE/Statin & Statin
Conclusions: The efficacy and safety of EZE & EZE/Statin in the elderly is similar to that in non-elderly. These results have implications when selecting lipid-lowering agents in elderly patients. PO44-690
THE EFFECT OF SIMVASTATIN/EZETIMIBE ADMINISTRATION IN THE MANAGEMENT OF PRIMARY HYPERLIPIDEMIA
E. Paschalidou 1 , Ap. Efthimiadis 1 , I. Efthimiadis 1 , V. Milioni 1 , A. Zafeiris 1 , A. Tavridou 2 , M. Raptopoulou-Gigi 1 . 1 Atherosclerosis Outpatient Clinic, 2nd Department of Internal Medicine, Hippocration General Hospital, Medical School, Aristotle University of Thessaloniki, Greece; 2 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece Background and aims: Simvastatin is a potent HMG-CoA inhibitor and ezetimibe is a potent inhibitor of cholesterol absorption. The last 2 years these two agents are administered combined in one pill for the better management of hyperlipidemias. We sought to determine the effect of the above combination in the management of primary hyperlipidemia. Methods: 30 subjects (18 men and 12 women) aged 54.25±12.38 years, with untreated primary hyperlipidemia (total cholesterol: 295.8±50.76 mg/dl, LDL-C: 210.1±48.36mg/dl) without active coronary artery disease were followed. All subjects received simvastatin/ezetimibe 40/10 mg one pill/day for three months. Before and after treatment lipid profile, liver enzymes, creatinine and urea were determined by the standard methods. Paired t-test was used to compare means at baseline and after treatment. Data are presented as mean±standard deviation. Results: Administration of the combination simvastatin/ezetimibe 40/10 mg/day statistically improve the lipid profile: total cholesterol decreased by 32%, LDL-C decreased by 42.6%, p<0.0001, triglycerides decreased by 22.8% p<0.0001 and HDL-C increased by 9.8% p<0.1. Liver enzymes levels were inside normal range so as CPK levels and renal function was not influenced. Conclusions: Combination hypolipidemic therapy using the simvastatin/ezetimibe 40/10 mg/day scheme did statistically improve lipid profile achieving the target of LDL-C for primary prevention (<130mg/dl), without any influence in renal or liver function. During the treatment no adverse event was reported.
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
POSTER SESSIONS
Background and Aims: Inflammation is central to coronary heart disease (CHD). Effects of ezetimibe as monotherapy or add-on to baseline statin-therapy on CRP, a marker of inflammation, and on LDL-C were examined. Methods: Results of randomized, placebo-controlled trials of ezetimibe 10mg in hypercholesterolemic adults were pooled in 2 analyses: six 12-week monotherapy trials (n=1372); seven 6-8 week add-on to baseline statin-therapy trials (n=3899). In patients with CRP<10mg/L, ANOVA was used to evaluate treatment effects on mean % changes from baseline in CRP and LDL-C. Spearman correlation coefficients among CRP and LDL-C levels at baseline and after treatment were calculated. Results: For both analyses, baseline characteristics were similar between groups. CRP reduction with ezetimibe monotherapy was numerically greater than placebo (treatment difference 6.0%, P=0.094), and with ezetimibe added to baseline statin-therapy was significantly greater than placebo (treatment difference 10.4%, P<0.001). Treatment effects were consistent across subgroups (age, gender, race, BMI, diabetes, metabolic syndrome, CHD, baseline CRP or lipids, and statin potency). In both analyses, LDL-C reduction with ezetimibe was significantly greater than placebo (P<0.001). Correlations were only significant, and weakly positive, between % changes from baseline in CRP and LDL-C when ezetimibe was added to baseline-statin-therapy. Conclusions: Although the effect of ezetimibe monotherapy on CRP was limited, when ezetimibe was added to baseline statin treatment, CRP reduction was enhanced. Correlations between CRP and LDL-C were weak or non-significant. Effects of ezetimibe on CRP were consistent across patient subgroups. The clinical relevance of changes in CRP to atherothrombotic risk needs further investigation.