Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial

Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48:438–45.

Article  CAS  Google Scholar 

Bohula, Erin A., et al. “Atherothrombotic risk stratification and the efficacy and safety of vorapaxar in patients with stable ischemic heart disease and previous myocardial infarction.” Circulation, vol. 134, no. 4, 2016, pp. 304–313., https://doi.org/10.1161/circulationaha.115.019861. Findings from this study suggest that stratification of patients based on baseline atherothrombotic risk may be helpful in clinical decision making for secondary prevention after MI. This includes the addition of lipid-lowering therapies for patients deemed high risk by a standardized scoring system.

Sudhop T, Lütjohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106:1943–8.

Article  CAS  Google Scholar 

Carson JA, et al. Dietary cholesterol and cardiovascular risk: a science advisory from the American Heart Association. Circulation. 2020;141:3. https://doi.org/10.1161/cir.0000000000000743.

Article  Google Scholar 

Sudhop T, Reber M, Tribble D, Sapre A, Taggart W, Gibbons P, Musliner T, von Bergmann K, Lütjohann D. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. J Lipid Res. 2009;50(10):2117–23. https://doi.org/10.1194/jlr.P900004-JLR200.

Article  CAS  Google Scholar 

Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004;93:1487–94.

Article  CAS  Google Scholar 

Cannon CP, Giugliano RP, Blazing MA, Harrington RA, Peterson JL, Sisk CM, et al. Rationale and design of IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008;156(5):826–32. https://doi.org/10.1016/j.ahj.2008.07.023.

Article  CAS  Google Scholar 

Cannon C, et al. Ezetimibe plus a statin after acute coronary syndromes. New England Journal of Medicine. 2015;373(15):1473–7. https://doi.org/10.1056/nejmc1509363.

Article  Google Scholar 

Bach RG, et al. Effect of simvastatin-ezetimibe compared with simvastatin monotherapy after acute coronary syndrome among patients 75 years or older. JAMA Cardiology. 2019;4(9):846. https://doi.org/10.1001/jamacardio.2019.2306.

Article  Google Scholar 

Kato ET, et al. Efficacy and safety of adding ezetimibe to statin therapy among women and men: insight from improve-it (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Journal of the American Heart Association. 2017;6:11. https://doi.org/10.1161/jaha.117.006901.

Article  CAS  Google Scholar 

Giugliano RP, et al. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus. Circulation. 2018;137(15):1571–82. https://doi.org/10.1161/circulationaha.117.030950.

Article  CAS  Google Scholar 

Bohula EA, et al. Prevention of stroke with the addition of ezetimibe to statin therapy in patients with acute coronary syndrome in improve-it (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2017;136(25):2440–50. https://doi.org/10.1161/circulationaha.117.029095.

Article  CAS  Google Scholar 

Eisen A, et al. The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the improve-it trial. European Heart Journal. 2016;37(48):3576–84. https://doi.org/10.1093/eurheartj/ehw377.

Article  CAS  Google Scholar 

Bonaca MP, et al. Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the improve-it trial. The Lancet Diabetes & Endocrinology. 2018;6(12):934–43. https://doi.org/10.1016/s2213-8587(18)30290-0.

Article  Google Scholar 

Oyama K, et al. Baseline low-density lipoprotein cholesterol and clinical outcomes of combining ezetimibe with statin therapy in improve-it. Journal of the American College of Cardiology. 2021;78(15):1499–507. https://doi.org/10.1016/j.jacc.2021.08.011.

Article  CAS  Google Scholar 

Stanifer JW, et al. Benefit of ezetimibe added to simvastatin in reduced kidney function. Journal of the American Society of Nephrology. 2017;28(10):3034–43. https://doi.org/10.1681/asn.2016090957.

Article  CAS  Google Scholar 

Ambrosy AP, et al. Natural history of patients postacute coronary syndrome based on heart failure status. The American Journal of Cardiology. 2018;122(9):1451–8. https://doi.org/10.1016/j.amjcard.2018.07.034.

Article  Google Scholar 

Mozaffarian, Dariush, et al “Heart disease and stroke statistics—2016 update.” Circulation, 2016 vol. 133, no. 4, 2016, https://doi.org/10.1161/cir.0000000000000350

Enriquez JR, Pratap P, Zbilut JP, Calvin JE, Volgman AS. Women tolerate drug therapy for coronary artery disease as well as men do, but are treated less frequently with aspirin, beta-blockers, or statins. Gend Med. 2008;5:53–61.

Article  Google Scholar 

Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM. Diabetes and mortality following acute coronary syndromes. JAMA. 2007;298:765–75.

Article  CAS  Google Scholar 

Bhatt DL, Eagle KA, Ohman EM, Hirsch AT, Goto S, Mahoney EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304:1350–135710.1001/jama.2010.1322.

Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.

Article  CAS  Google Scholar 

Wiseman A, Waters DD, Walling A, Pelletier GB, Roy D, Theroux P. Long-term prognosis after myocardial infarction in patients with previous coronary artery bypass surgery. J Am Coll Cardiol. 1988;12:873–80.

Article  CAS  Google Scholar 

Suárez C, et al. Influence of polyvascular disease on cardiovascular event rates. Insights from the REACH Registry. Vascular Medicine. 2009;15(4):259–65. https://doi.org/10.1177/1358863x10373299.

Article  Google Scholar 

Domanski MJ, Tian X, Wu CO, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2020;76:1507–16.

Article  CAS  Google Scholar 

Fruchart, Jean-Charles, et al. “New risk factors for atherosclerosis and patient risk assessment.” Circulation, vol. 109, no. 23_suppl_1, 2004, https://doi.org/10.1161/01.cir.0000131513.33892.5b

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

Article  CAS  Google Scholar 

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Cholesterol Treatment Trialists’ (CTT) collaborators: efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.

Article  CAS  Google Scholar 

Velazquez EJ, Francis GS, Armstrong PW, Aylward PE, Diaz R, O’Connor CM, et al. Valiant registry. An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry. Eur Heart J. 2004;25:1911–9.

Article  Google Scholar 

Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. The Lancet. 2010;376(9753):1670–81. https://doi.org/10.1016/s0140-6736(10)61350-5.

Article  Google Scholar 

Byeong-Keuk K, et al. Long-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. The Lancet. 2022;400(10349):380–90. https://doi.org/10.1016/s0140-6736(22)00916-3.

Article  CAS  Google Scholar 

Mach, François, et al. “2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.” European Heart Journal, vol. 41, no. 1, 2019, pp. 111–188., https://doi.org/10.1093/eurheartj/ehz455. This publication reviews the European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidemia. They recommend the addition of ezetimibe for patients with dyslipidemia who are not at goal on maximally tolerated statin therapy or who otherwise have intolerance or contraindication to these medications. This recommendation is largely based on the findings of IMPROVE-IT which show efficacy and safety of the addition of ezetimibe to simvastatin for the management of hyperlipidemia.

Grundy, Scott M., et al. “2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APHA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.” Circulation, vol. 139, no. 25, 2019, https://doi.org/10.1161/cir.0000000000000625. This publication highlights the American guidelines for the management of hyperlipidemia with the recommendation for the addition of ezetimibe for patients who are not at established goals on statin monotherapy. These recommendations reflect the findings of IMPROVE-IT which demonstrated the safety and efficacy of this combination therapy.

Lloyd-Jones DM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2022;80(14):1366–418.

Article  Google Scholar 

留言 (0)

沒有登入
gif