Preventive cardiologyReview of Side-Effect Profile of Combination Ezetimibe and Statin Therapy in Randomized Clinical Trials
Section snippets
Methods
We performed this study in accordance with the Quality of Reporting of Meta-analyses Statement and recommendations for assessing harm in randomized clinical trials.2 Eligible studies were identified by searching MEDLINE (1966 to July 2006), EMBASE (1980 to July 2006), the Cochrane Library, the National Institutes of Health Clinical Trials Website, and relevant bibliographies. A combination of medical subject headings and text terms ezetimibe, zetia, and vytorin was used.
We included
Results
We identified 312 potentially relevant studies. Of these, 18 studies met our inclusion/exclusion criteria and were assessed in this study. A total of 14,471 patients were evaluated: 503 were randomly assigned to ezetimibe monotherapy; 7,911, to ezetimibe-statin combination therapy; and 6,057, to statin monotherapy. The method quality of the studies included was high, with an average Jadad score of 4.6 points.3 The statins assessed were atorvastatin (4 trials; 22%; n = 1,885), lovastatin (1
Discussion
Ezetimibe was touted as a novel LDL-lowering agent that provided substantial LDL lowering and, when used in combination with a statin, could achieve lower LDL targets through the complimentary mechanism of action of these 2 drugs.8, 15, 26 In 1 study, 86% of patients on combination therapy versus 68% of patients on statin monotherapy (p <0.01) reached National Cholesterol Education Program Adult Treatment Panel III27–recommended LDL targets.26 In addition, ezetimibe may be used to achieve LDL
References (31)
- et al.
Risks associated with statin therapy: a systematic overview of randomized clinical trials
Circulation
(2006) - et al.
Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statementQuality of Reporting of Meta-analyses
Lancet
(1999) - et al.
Assessing the quality of reports of randomized clinical trials: is blinding necessary?
Control Clin Trials
(1996) - et al.
Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin
Am Heart J
(2004) - et al.
LDL-C goal attainment with the addition of ezetimibe to ongoing simvastatin treatment in coronary heart disease patients with hypercholesterolemia
Curr Med Res Opin
(2005) - et al.
Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease
Int J Clin Pract
(2005) - et al.
Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia
Am J Cardiol
(2003) - et al.
Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia
J Am Coll Cardiol
(2002) - et al.
Long-term safety and tolerability profile of ezetimibe and atorvastatin coadministration therapy in patients with primary hypercholesterolaemia
Int J Clin Pract
(2004) - et al.
Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease
Int J Cardiol
(2005)
Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease
Int J Clin Pract
Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial
Eur Heart J
A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the Ezetimibe Add-on to Statin for Effectiveness (EASE) Trial
Mayo Clin Proc
Long-term safety and tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study
Clin Ther
Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial
Circulation
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PCSK9 inhibitor, ezetimibe, and bempedoic acid: Evidence-based therapies for statin-intolerant patients
2023, Progress in Cardiovascular DiseasesSpecial Patient Populations: Children and Adolescents
2023, Clinical Lipidology: A Companion to Braunwald's Heart DiseaseLong-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial
2022, The LancetCitation Excerpt :Considering a 15% loss to follow-up, a total of 3780 patients were required to prove our hypothesis. For the secondary objective, the achievement of LDL cholesterol of less than 70 mg/dL at 1 year was 31% in the simvastatin and 51% in the simvastatin–ezetimibe groups, in the IMPROVE-IT trial, and the LDL cholesterol-lowering effect of simvastatin–ezetimibe 40–10 mg was known to be similar to that of rosuvastatin 20 mg.22,24 Therefore, as a clinically important difference, the proportion of participants achieving LDL cholesterol of less than 70 mg/dL was presumed to be 70% in the combination therapy group and 50% in the high-intensity statin monotherapy group.
Lipid-Modifying Agents, From Statins to PCSK9 Inhibitors: JACC Focus Seminar
2020, Journal of the American College of CardiologyCitation Excerpt :Ezetimibe at the recommended 10-mg daily dose produces a mean reduction in LDL cholesterol (net of placebo) of 19% as monotherapy and 23% from the on-statin baseline when added to statin treatment (35). Several large long-term cardiovascular outcome studies (4,36,37), as well as earlier studies, demonstrated a safety and tolerability profile not detectably different from placebo (38). Specifically, muscle injury (myopathy, or its more severe form, rhabdomyolysis) does not appear to be an adverse effect of ezetimibe: there has been no excess over placebo of cases in large RCTs, and most cases reported during post-marketing surveillance have been in patients also treated with a statin.
LDL-cholesterol: The lower the better
2019, Clinica e Investigacion en Arteriosclerosis
Dr. Foody is on the advisory boards for Merck, Pfizer, and BMS/Sanofi and has received speaker honoraria from the same. Dr. Mann is supported by grants from the National Institutes of Health, Bethesda, Maryland, is a consultant for Acorn Cardiovascular, St. Paul, MN, and Medtronic, Minneapolis, MN, and holds Medtronic stocks.