The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Enrico P. Veltri - One of the best experts on this subject based on the ideXlab platform.
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Long-term safety and tolerability of Ezetimibe coadministered with Simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study
Current medical research and opinion, 2008Co-Authors: John Strony, Bo Yang, Mary E. Hanson, Enrico P. VeltriAbstract:ABSTRACTObjectives: To assess the long-term safety and tolerability and to further evaluate the effect of Ezetimibe Plus Simvastatin on LDL-C, HDL-C, and triglyceride levels in subjects with primary hypercholesterolemia.Methods: This was a 12-month, double-blind, placebo-controlled extension study that enrolled patients with primary hypercholesterolemia who had successfully completed the 12-week, double-blind, placebo-controlled trial of Ezetimibe coadministered with Simvastatin. The initial dose administered to patients in the extension was Ezetimibe 10 mg coadministered with Simvastatin 10 mg with the option to up-titrate statin dosage if LDL-C goals were not met. Safety and tolerability were assessed through clinical and laboratory adverse experiences (AEs). Changes from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels were measured.Results: Overall, 87 patients were randomized to receive Ezetimibe + s...
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comparison of Ezetimibe Plus Simvastatin versus Simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia design and rationale of the Ezetimibe and Simvastatin in hypercholesterolemia enhances atherosclerosis regression
American Heart Journal, 2005Co-Authors: John J P Kastelein, Philip T. Sager, Eric De Groot, Enrico P. VeltriAbstract:Background Lipid lowering through statin therapy significantly reduces the risk of cardiovascular events. The ENHANCE study is an international 2-year, randomized, double-blind, controlled trial designed to test the hypothesis that treatment of hypercholesterolemia by use of 2 complementary agents, Ezetimibe (a specific cholesterol absorption inhibitor) and Simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor), will result in larger beneficial effects on carotid artery intima-media thickness (CA IMT) than Simvastatin monotherapy. Methods The study will recruit 725 men and women with heterozygous familial hypercholesterolemia. After a placebo washout period, participants are randomized to receive daily administration of either Simvastatin 80 mg and Ezetimibe 10 mg or Simvastatin 80 mg and placebo. The ENHANCE trial uses novel state-of-the-art single-frame digital image acquisition and rigorous quality assurance and control. Results The primary end point is mean change from baseline to 2 years in CA IMT, using composite measures from the right and left far wall common carotid artery, carotid bulb, and internal carotid artery. Secondary end points include (1) the proportion of participants who exhibit reductions in CA IMT, (2) the change in maximum far wall IMT, (3) the proportion of participants who develop new carotid artery plaques, and (4) the changes in carotid Plus common femoral artery IMT. Conclusions This study addresses the question of whether a regimen that uses drugs with different mechanisms of action will be of further benefit in terms of atherosclerosis reduction compared to statin monotherapy.
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Effects of Ezetimibe coadministered with Simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients.
Atherosclerosis, 2004Co-Authors: Philip T. Sager, Leslie Lipka, Ramachandran Suresh, John Strony, Bo Yang, Rachel Capece, Yale B. Mitchel, Enrico P. VeltriAbstract:Abstract Objective: This study assessed the effect of coadministration of Ezetimibe and Simvastatin on high sensitivity C-reactive protein (hs-CRP) in a large subject cohort (N = 1089). Methods: Data were combined from two nearly identical prospective trials. After dietary stabilization, washout period, and placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) ≥ 3.75–6.50 mmol/l and triglycerides (TG) ≤ 4.0 mmol/l were randomized to one of the following daily treatments for 12 weeks: Ezetimibe 10 mg; Simvastatin monotherapy (10, 20, 40, or 80 mg); Ezetimibe 10 mg Plus Simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the percent change in hs-CRP for the pooled Ezetimibe Plus Simvastatin versus Simvastatin monotherapy cohorts. Results: Ezetimibe coadministered with Simvastatin more than doubled the hs-CRP reduction compared to Simvastatin monotherapy (−33.3% versus −14.3%, p Conclusion: In this large subject cohort, Ezetimibe coadministered with Simvastatin significantly reduced hs-CRP, suggesting a possible additional anti-inflammatory/anti-atherosclerotic action of combination therapy compared to Simvastatin monotherapy.
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Effect of coadministration of Ezetimibe and Simvastatin on high-sensitivity C-reactive protein.
The American journal of cardiology, 2003Co-Authors: Philip T. Sager, Leslie Lipka, Ramachandran Suresh, L Melani, John Strony, Bo Yang, Enrico P. VeltriAbstract:This study assessed the effect of Ezetimibe coadministered with Simvastatin on high-sensitivity C-reactive protein (hs-CRP) in patients with primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol > or =145 and < or =250 mg/dl and triglycerides < or =350 mg/dl were randomized to one of these daily treatments for 12 consecutive weeks: Ezetimibe 10 mg; Simvastatin monotherapy (10, 20, 40, or 80 mg); Ezetimibe 10 mg Plus Simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the change in hs-CRP for the pooled Ezetimibe Plus Simvastatin versus Simvastatin monotherapy groups. Ezetimibe Plus Simvastatin significantly reduced median hs-CRP levels compared with Simvastatin monotherapy (-34.8% vs -18.2%, p
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Ezetimibe coadministered with Simvastatin in patients with primary hypercholesterolemia
Journal of the American College of Cardiology, 2002Co-Authors: Michael H. Davidson, Leslie Lipka, Alexandre Lebeaut, Ramachandran Suresh, L Melani, Thomas J Mcgarry, Robert Bettis, Steven Sun, Enrico P. VeltriAbstract:Abstract Objectives The purpose of this study was to assess the efficacy and safety of Ezetimibe administered with Simvastatin in patients with primary hypercholesterolemia. Background Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. Methods After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) ≥145 mg/dl to ≤250 mg/dl and triglycerides (TG) ≤350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: Ezetimibe 10 mg; Simvastatin 10, 20, 40, or 80 mg; Ezetimibe 10 mg Plus Simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled Ezetimibe Plus Simvastatin groups versus pooled Simvastatin groups. Results Ezetimibe Plus Simvastatin significantly improved LDL-C (p Conclusions When coadministered with Simvastatin, Ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of Ezetimibe with Simvastatin was well tolerated and comparable to statin alone.
Debra Kush - One of the best experts on this subject based on the ideXlab platform.
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treatment of high risk patients with Ezetimibe Plus Simvastatin co administration versus Simvastatin alone to attain national cholesterol education program adult treatment panel iii low density lipoprotein cholesterol goals
American Journal of Cardiology, 2004Co-Authors: Ted Feldman, Michael J Koren, William Insull, James M Mckenney, Helmut G Schrott, Andrew Lewin, Sukrut Shah, Michelle Sidisin, Meehyung Cho, Debra KushAbstract:This study assessed whether the co-administration of Ezetimibe and Simvastatin would be more effective than Simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of /=130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: Simvastatin 20 mg (n = 253), Ezetimibe 10 mg Plus Simvastatin 10 mg (n = 251), Ezetimibe 10 mg Plus Simvastatin 20 mg (n = 109), and Ezetimibe 10 mg Plus Simvastatin 40 mg (n = 97). In all groups, patients not at goal had their Simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (<100 mg/dl) after 5 weeks of treatment. Ezetimibe Plus any dose of Simvastatin produced greater reductions in LDL cholesterol and allowed more patients to achieve goal after 5 weeks (p <0.001) and at the end of the study (p <0.001) than Simvastatin 20 mg alone. At 5 weeks, 75%, 83%, and 87% of patients receiving Ezetimibe Plus Simvastatin 10, 20, and 40 mg had LDL cholesterol <100 mg/dl compared with 46% of patients receiving Simvastatin 20 mg. In patients who started on Ezetimibe Plus Simvastatin 10, 20 and 40 mg, 33%, 22%, and 12%, respectively, required Simvastatin titration during the study compared with 68% of patients who started on Simvastatin 20 mg. The corresponding median Simvastatin doses used were 10, 20, 40, and 40 mg, respectively. Ezetimibe Plus Simvastatin was well tolerated, with an overall safety profile similar to that of Simvastatin monotherapy. Thus, through the dual inhibition of cholesterol absorption and synthesis, Ezetimibe Plus Simvastatin allowed more patients to reach LDL cholesterol <100 mg/dl at a lower Simvastatin dose and with fewer dose titrations than Simvastatin monotherapy.
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Treatment of High-Risk patients with Ezetimibe Plus Simvastatin Co-Administration versus Simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III Low-Density lipoprotein cholesterol goals
The American journal of cardiology, 2004Co-Authors: Ted Feldman, Michael J Koren, William Insull, James M Mckenney, Helmut G Schrott, Sukrut Shah, Michelle Sidisin, Meehyung Cho, Andrew J. Lewin, Debra KushAbstract:This study assessed whether the co-administration of Ezetimibe and Simvastatin would be more effective than Simvastatin monotherapy in allowing high-risk patients to achieve a low-density lipoprotein (LDL) cholesterol goal of /=130 mg/dl and meeting National Cholesterol Education Program Adult Treatment Panel III criteria for coronary heart disease (CHD) or CHD risk equivalent were randomized to 1 of 4 daily treatments for 23 weeks: Simvastatin 20 mg (n = 253), Ezetimibe 10 mg Plus Simvastatin 10 mg (n = 251), Ezetimibe 10 mg Plus Simvastatin 20 mg (n = 109), and Ezetimibe 10 mg Plus Simvastatin 40 mg (n = 97). In all groups, patients not at goal had their Simvastatin doses doubled at weeks 6, 12, and/or 18, up to a maximum of 80 mg. The primary efficacy objective was LDL cholesterol goal attainment (
Sabina A Murphy - One of the best experts on this subject based on the ideXlab platform.
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reply adding Ezetimibe to Simvastatin for the secondary prevention of cardiovascular disease is it useful
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Andrew M Tershakovec, Eugene BraunwaldAbstract:In response to Drs. Mascitelli and Goldstein, we previously reported in the primary publication of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) that there was no difference between Ezetimibe Plus Simvastatin as compared with Simvastatin alone with respect to
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reduction in total cardiovascular events with Ezetimibe Simvastatin post acute coronary syndrome the improve it trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel Isaza, Jose LopezsendonAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
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Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel IsazaAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
Michael A Blazing - One of the best experts on this subject based on the ideXlab platform.
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Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function
Journal of the American Society of Nephrology : JASN, 2017Co-Authors: John W. Stanifer, Christopher P Cannon, David M. Charytan, Jennifer White, Yuliya Lokhnygina, Matthew T. Roe, Michael A BlazingAbstract:Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with Ezetimibe Plus Simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (Ezetimibe Plus Simvastatin versus Simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
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reply adding Ezetimibe to Simvastatin for the secondary prevention of cardiovascular disease is it useful
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Andrew M Tershakovec, Eugene BraunwaldAbstract:In response to Drs. Mascitelli and Goldstein, we previously reported in the primary publication of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) that there was no difference between Ezetimibe Plus Simvastatin as compared with Simvastatin alone with respect to
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reduction in total cardiovascular events with Ezetimibe Simvastatin post acute coronary syndrome the improve it trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel Isaza, Jose LopezsendonAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
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Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel IsazaAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
Christopher P Cannon - One of the best experts on this subject based on the ideXlab platform.
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Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function
Journal of the American Society of Nephrology : JASN, 2017Co-Authors: John W. Stanifer, Christopher P Cannon, David M. Charytan, Jennifer White, Yuliya Lokhnygina, Matthew T. Roe, Michael A BlazingAbstract:Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with Ezetimibe Plus Simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (Ezetimibe Plus Simvastatin versus Simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.
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reply adding Ezetimibe to Simvastatin for the secondary prevention of cardiovascular disease is it useful
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Andrew M Tershakovec, Eugene BraunwaldAbstract:In response to Drs. Mascitelli and Goldstein, we previously reported in the primary publication of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) that there was no difference between Ezetimibe Plus Simvastatin as compared with Simvastatin alone with respect to
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reduction in total cardiovascular events with Ezetimibe Simvastatin post acute coronary syndrome the improve it trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel Isaza, Jose LopezsendonAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
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Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial
Journal of the American College of Cardiology, 2016Co-Authors: Sabina A Murphy, Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Yuliya Lokhnygina, Jennifer A White, Craig J Reist, Erin A Bohula, Daniel IsazaAbstract:Abstract Background Intensive low-density lipoprotein cholesterol therapy with Ezetimibe/Simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/Simvastatin. Objectives This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with Ezetimibe/Simvastatin therapy. Methods All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive Ezetimibe/Simvastatin or placebo/Simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Results Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with Ezetimibe/Simvastatin vs placebo/Simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Conclusions Lipid-lowering therapy with Ezetimibe Plus Simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878 )
