Lipid Lowering in Patients 75 Years and Older

Overview

Journal World J Cardiol

Publisher Baishideng Publishing Group

Specialty Cardiology & Vascular Diseases

Date 2021 Nov 10

PMID 34754397

Authors

Umidakhon Makhmudova

P Christian Schulze

Harry R Davis

Oliver Weingartner

Affiliations

Soon will be listed here.

Abstract

More than twenty years ago, knowledge about the importance of cholesterol absorption and the potential therapeutic effect of its inhibition led to the discovery and clinical application of the first and only cholesterol absorption inhibitor to date - ezetimibe. Since then, ezetimibe has become a well-recognized player in lipid-lowering therapy. Recent findings of IMPROVE-IT and EWTOPIA 75 imply that elderly patients over the age of 75 years in particular benefit from ezetimibe. This review summarizes the evidence, discusses the possible underlying pathophysiological mechanisms and calls for a change in future dyslipidemia guidelines.

References

Miettinen T, Gylling H, Strandberg T, Sarna S . Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ. 1998; 316(7138):1127-30. PMC: 28514. DOI: 10.1136/bmj.316.7138.1127. View

Han B, Sutin D, Williamson J, Davis B, Piller L, Pervin H . Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017; 177(7):955-965. PMC: 5543335. DOI: 10.1001/jamainternmed.2017.1442. View

Bach R, Cannon C, Giugliano R, White J, Lokhnygina Y, Bohula E . Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019; 4(9):846-854. PMC: 6647004. DOI: 10.1001/jamacardio.2019.2306. View

Kosoglou T, Statkevich P, Johnson-Levonas A, Paolini J, Bergman A, Alton K . Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005; 44(5):467-94. DOI: 10.2165/00003088-200544050-00002. View

Murphy S, Cannon C, Blazing M, Giugliano R, Tershakovec A, Braunwald E . Reply: Personalize and Optimize Lipid-Lowering Therapies. J Am Coll Cardiol. 2016; 68(3):326. DOI: 10.1016/j.jacc.2016.04.043. View

Yi S, Yi J, Ohrr H . Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults. Sci Rep. 2019; 9(1):1596. PMC: 6367420. DOI: 10.1038/s41598-018-38461-y. View

Weingartner O, Lutjohann D, Elsasser A . Personalize and Optimize Lipid-Lowering Therapies. J Am Coll Cardiol. 2016; 68(3):325-326. DOI: 10.1016/j.jacc.2016.02.086. View

Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K . Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial. J Cardiol. 2015; 66(4):353-8. DOI: 10.1016/j.jjcc.2014.12.011. View

Shepherd J, Blauw G, Murphy M, Bollen E, Buckley B, Cobbe S . Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360(9346):1623-30. DOI: 10.1016/s0140-6736(02)11600-x. View

10.

Matthan N, Lichtenstein A . Approaches to measuring cholesterol absorption in humans. Atherosclerosis. 2004; 174(2):197-205. DOI: 10.1016/S0021-9150(03)00248-X. View

11.

Endo A . The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res. 1992; 33(11):1569-82. View

12.

Weingartner O, Weingartner N, Scheller B, Lutjohann D, Graber S, Schafers H . Alterations in cholesterol homeostasis are associated with coronary heart disease in patients with aortic stenosis. Coron Artery Dis. 2009; 20(6):376-82. DOI: 10.1097/MCA.0b013e32832fa947. View

13.

Weingartner O, Lutjohann D, Bohm M, Laufs U . Relationship between cholesterol synthesis and intestinal absorption is associated with cardiovascular risk. Atherosclerosis. 2010; 210(2):362-5. DOI: 10.1016/j.atherosclerosis.2010.01.003. View

14.

Weingartner O, Lutjohann D, Vanmierlo T, Muller S, Gunther L, Herrmann W . Markers of enhanced cholesterol absorption are a strong predictor for cardiovascular diseases in patients without diabetes mellitus. Chem Phys Lipids. 2011; 164(6):451-6. DOI: 10.1016/j.chemphyslip.2011.03.008. View

15.

Hagiwara N, Kawada-Watanabe E, Koyanagi R, Arashi H, Yamaguchi J, Nakao K . Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J. 2017; 38(29):2264-2276. PMC: 5837267. DOI: 10.1093/eurheartj/ehx162. View

16.

Postmus I, Trompet S, Deshmukh H, Barnes M, Li X, Warren H . Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat Commun. 2014; 5:5068. PMC: 4220464. DOI: 10.1038/ncomms6068. View

17.

Helgadottir A, Thorleifsson G, Alexandersson K, Tragante V, Thorsteinsdottir M, Eiriksson F . Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease. Eur Heart J. 2020; 41(28):2618-2628. PMC: 7377579. DOI: 10.1093/eurheartj/ehaa531. View

18.

Weingartner O, Patel S, Lutjohann D . It's time to personalize and optimize lipid-lowering therapy. Eur Heart J. 2020; 41(28):2629-2631. DOI: 10.1093/eurheartj/ehaa445. View

19.

Higuchi K, Kitagawa K, Kogishi K, Takeda T . Developmental and age-related changes in apolipoprotein B mRNA editing in mice. J Lipid Res. 1992; 33(12):1753-64. View

20.

Weingartner O, Sijbrands E, Lutjohann D . Interpreting the Benefit of Simvastatin-Ezetimibe in Patients 75 Years or Older. JAMA Cardiol. 2020; 5(2):234. DOI: 10.1001/jamacardio.2019.5197. View