Statins for primary prevention of atherosclerotic cardiovascular disease in people 75 years of age and older

doi:10.12092/j.issn.1009-2501.2020.09.017

Abstract

Abstract: Statins are important drugs for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). The role and status of statins in ASCVD secondary prevention have been established, but the application of statins in ASCVD primary prevention in the elderly is controversial, especially in the elderly aged 75 years and older. The evidence for primary prevention with statins is not adequate. It should be cautious to initiate statins for primary prevention, because of the frailty, multicomobidity, polypharmacy and the limited life expectancy of the elderly may increase the risk of statins adverse reactions. The recent clinical studies and guidelines of statin primary prevention in the elderly population especially in aged 75 years and older have been reviewed in the paper. Making decisions based on fully evaluating the patients' ratio of benefits and risk with patients and implement statin individualized treatment strategies are emphasized.

Key words: statin, the elderly, atherosclerotic cardiovascular disease (ASCVD), primary prevention

CLC Number:

R541.4

YANG Ming, DONG Xiaowen, HONG Huashan. Statins for primary prevention of atherosclerotic cardiovascular disease in people 75 years of age and older[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(9): 1074-1080.

References ［48］

［1］	Akushevich I, Kravchenko J, Ukraintseva S, et al. Age patterns of incidence of geriatric disease in the U.S. elderly population: Medicare-based analysis ［J］. J Am Geriatr Soc, 2012, 60(2): 323-327.
［2］	Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease.1.Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel ［J］. Eur Heart J, 2017, 38(32): 2459-2472.
［3］	Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial ［J］. Lancet, 2002, 360(9346): 1623-1630.
［4］	Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial ［J］. Lancet, 2002, 360(9326): 7-22.
［5］	Armitage J, Baigent C, Barnes E, et al. Efficacy and safety of statin therapy in older people:a meta-analysis of individual participant data from 28 randomised controlled trials ［J］. Lancet, 2019, 393(10170): 407-415.
［6］	Vallejo-Vaz AJ, Robertson M, Catapano AL, et al. LDL-cholesterol lowering for the primary prevention of cardiovascular disease among men with primary elevations of LDL-cholesterol levels of 190 mg/dL or above: analyses from the WOSCOPS 5-year randomised trial and 20-year observational follow-up ［J］. Circulation, 2017, 136(20): 1-25.
［7］	Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA):a multicentre randomized controlled trial ［J］. Lancet, 2003, 361(9364): 1149-1158.
［8］	Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein ［J］. N Engl J Med, 2008, 359(21): 2195-2207.
［9］	Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease ［J］. N Engl J Med, 2016, 374(21): 2021-2031.
［10］	Lemaitre RN, Psaty BM, Heckbert SR, et al. Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study ［J］. Arch Intern Med, 2002, 162(12): 1395-1400.
［11］	Ridker PM, Lonn E, Paynter NP, et al. Primary prevention with statin therapy in the elderly: new meta-analyses from the contemporary JUPITER and HOPE-3 randomized trials ［J］. Circulation, 2017, 135(20): 1979-1981.
［12］	McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly［J］. N Engl J Med, 2018, 379(16): 1499-1508.
［13］	Zhou Z, Ofori-Asenso R, Curtis AJ, et al. Association of statin use with disability- free survival and cardiovascular disease among healthy older adults ［J］. J Am Coll Cardiol, 2020, 76: 17-27.
［14］	Orkaby AR, Driver JA, Ho YL, et al. Association of Statin use with all-cause and cardiovascular mortality in US veterans 75 years and older ［J］. JAMA, 2020, 324(1): 68-78.
［15］	Kim K, Lee CJ, Shim CY, et al. Statin and clinical outcomes of primary prevention in individuals aged>75 years: the SCOPE-75 study ［J］. Atherosclerosis, 2019, 284: 31-36.
［16］	Ramos R, Comas-Cufí M, Martí-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study ［J］. BMJ, 2018, 362: 1-12.
［17］	Orkaby AR, Gaziano JM, Djousse L, et al. Statins for primary prevention of cardiovascular events and mortality in older men ［J］. J Am Geriatr Soc, 2017, 65(11): 2362-2368.
［18］	Giral P, Neumann A, Weill A, et al. Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France ［J］. Eur Heart J, 2019, 40(43): 3516-3525.
［19］	ClinicalTrials.gov. A clinical trial of Statin therapy for reducing events in the elderly (STAREE) ［EB/OL］. (2019-03-12) ［2019-03-12］. https://clinicaltrials. gov/ct2/show/ NCT02099123.
［20］	ClinicalTrials.gov. Statins in the elderly (SITE) ［EB/OL］. ［2020-02-07］. https://clinicaltrials.gov/ct2/ show/NCT02547883.
［21］	Zhou Z, Albarqouni L, Curtis AJ, et al. The safety and tolerability of statin therapy in primary prevention in older adults: a systematic review and meta-analysis ［J］. Drugs Aging, 2020, 37(3): 175-185.
［22］	Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: a scientific statement from the american heart association ［J］. Arterioscler Thromb Vasc Biol, 2018, 38: e01-e44.
［23］	Scott D, Blizzard L, Fell J, et al. Statin therapy, muscle function and falls risk in community-dwelling older adults ［J］. QJM, 2009, 102(9): 625-633.
［24］	Glynn RJ, Koenig W, Nordestgaard BG, et al. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial ［J］. Ann Intern Med, 2010, 152(8): 488-496,W174.
［25］	Iwere RB, Hewitt J. Myopathy in older people receiving statin therapy:a systematic review and meta-analysis ［J］. Br J Clin Pharmacol, 2015, 80(3): 363-371.
［26］	Guo M, Zhao J, Zhai Y, et al. A prospective study of hepatic safety of statins used in very elderly patients ［J］. BMC Geriatr, 2019, 19(1): 1-7.
［27］	Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial ［J］. Lancet, 2012, 380: 565-571.
［28］	Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes:a collaborative meta-analysis of randomised statin trials ［J］. Lancet, 2010, 375: 735-742.
［29］	Evans MA, Golomb BA. Statin-associated adverse cognitive effects: survey results from 171 patients ［J］. Pharmacotherapy, 2009, 29(7): 800-811.
［30］	Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss ［J］. Pharmacotherapy, 2001, 21(6): 767-769.
［31］	Wagstaff LR, Mitton MW, Arvik BM, et al. Statin-associated memory loss: analysis of 60 case reports and review of the literature ［J］. Pharmacotherapy, 2003, 23(7): 871-880.
［32］	Ott BR, Daiello LA, Dahabreh IJ, et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials ［J］. J Gen Intern Med, 2015, 30(3): 348-358.
［33］	Samaras K, Makkar SR, Crawford JD, et al. Effects of statins on memory, cognition, and brain volume in the elderly ［J］ .J Am Coll Cardiol, 2019, 74(21): 2554-2568.
［34］	中国老年保健医学研究会, 老年内分泌与代谢病分会, 中国毒理学会临床毒理专业委员会. 老年人多重用药安全管理专家共识［J］. 中国糖尿病杂志, 2018, 26(9): 705-717.
［35］	孙晓琳, 赵娣, 李军袖, 等. 有机阴离子转运多肽OATP1B1、OATP1B3的基因多态性及其介导的药物相互作用研究进展［J］. 中国临床药理学与治疗学, 2015, 20(11): 1296-1301.
［36］	Wiggins BS, Saseen JJ, Page RL, et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American heart association ［J］. Circulation, 2016, 134(21): e1-e28.
［37］	Downs JR, O'Malley PG. Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2014 U.S. department of veterans affairs and U.S. department of defense clinical practice guideline ［J］. Ann Intern Med, 2015, 163(4): 291-297.
［38］	National Institute for Health and Clinical Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease ［S］. NICE Clinical Guideline, No.181. London: National Institute for Health and Care Excellence (UK); 2014 07.
［39］	Anderson TJ, Gregoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult ［J］. Can J Cardiol, 2016, 32(11): 1263-1282.
［40］	Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement ［J］. JAMA, 2016, 316(19): 1997-2007.
［41］	Grundy SM, Stone NJ, Bailey AL, 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 ［J］. J Am Coll Cardiol, 2019, 73(24): e285-350.
［42］	Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease ［J］. Circulation, 2019, 140(11): 1-101.
［43］	Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk ［J］. Eur Heart J, 2020, 41(1): 1-78.
［44］	Mortensen MB, Falk E. Primary prevention with statins in the elderly ［J］. J Am Coll Cardiol, 2018, 71(1): 85-94.
［45］	Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias ［J］. Eur Heart J, 2016, 37(39): 2999-3058.
［46］	海峡两岸医药卫生交流协会老年医学专业委员会. ≥75岁老年患者血脂异常管理的专家共识［J］. 中国心血管杂志, 2020, 25(3): 201-209.
［47］	Pilotto A, Custodero C, Maggi S, et al. A multidimensional approach to frailty in older people ［J］. Ageing Res Rev, 2020, 60: 1-9.
［48］	陈旭娇, 严静, 王建业, 等. 中华医学会老年医学分会.老年综合评估技术应用中国专家共识［J］. 中华老年医学杂志, 2017, 36(5): 471-477.

[1]	LI Qinghua, ZHAO Yan, ZHAO Haigang, GAO Pengfei, XU Bingxin. Value of ABCB1 G2677T gene polymorphism detection in lipid-lowering therapy with atorvastatin in patients suffered from ischemic stroke [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(6): 633-640.
[2]	ZHAO Lu, LI Fuyong, WEN Binhong, LI Daowei. Effects of stains on hyperlipidemia and pain relieve of patients with chronic migraine [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(6): 671-675.
[3]	TANG Zizhao, NIE Fangqin, YAN Xin, FU Yangxia, HUANG Jun, WANG Xia, GUO Ren. Effect of Atglistatin on PA-induced VSMCs proliferation and ATGL expression [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(1): 29-35.
[4]	LIN Xueyan, LIN Zhihui, HUANG Huping. Effect of terlipressin on renal function in cirrhotic patients with esophageal gastric varices bleeding and normal baseline renal function [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(7): 775-784.
[5]	LIANG Meifang, CHEN Qingzhuang, YANG Peiqun, WANG Yong. Efficacy and safety of generic and branded atorvastatin in patients with ischemic stroke/transient ischemic attack: A real-world study [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(7): 785-792.
[6]	ZENG Xiaofan, XU Yiqi, LIU Shu, WU Qian, LI Zibao, HE Junjun, JIN Yuelong, ZHAO Yongli, HE Chunling, GAO Jialin. Retrospectively analysis of the effect of low-dose aspirin on primary prevention of non-fatal myocardial infarction and cerebral infarction in patients with type 2 diabetes mellitus [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 665-671.
[7]	YUN Qiang, DONG Xuejia, WANG Mengjiao, LIU Yahong, WANG Zhiguang, JIANG Mingfang. Rosuvastatin regulates cerebral I/R damage to neurons by UCP2-SIRT3 signal [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(2): 144-153.
[8]	WANG Fengling, MENG Xiangyun, CHEN Zhengxu, CAO Rongjuan, HE Zhengmin, YE Xi, WANG Cong, LI Qi. Analysis on genetic polymorphism of SLCO1B1 and ApoE in patients with cardiovascular diseases of Han nationality in Anhui area and its clinical significance for individualized use of statins [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(1): 40-48.
[9]	RU Caiwang, YUAN Tianming, YANG Bingfen, WU Fugen, LIN Yingrong, MO Miaojun. Effects of imipenem-cilastatin sodium combined with immunoglobulin on serum PCT, hs-CRP and TNF-α in children with baby sepsis complicated with disseminated intravascular coagulation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(5): 559-565.
[10]	XIE Xiangmei, HUANG Zhihong, LIU Xiaoju, XUE Bing, LAN Baozhu. Effects of atorvastatin and folic acid tablets on homocysteine and carotid atherosclerosis in patients with type H hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(4): 455-459.
[11]	LI Jiadan，LU Chen. Synergistic effects of Cortex Mori alkaloids combined with Simvastatin in rats with hyperlipidaemia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(3): 278-284.
[12]	Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, GCP Center Phase I Clinical Trial Ward, Shenyang , Liaonning, China. Bioequivalence of rosuvastatin calcium tablets in Chinese healthy subjects [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(12): 1369-1375.
[13]	SUN Qing, SUN Jianfang, LI Li, CHANG Huichao, ZHOU Quan. Effects of Wuzhi capsule on the pharmacokinetics of simvastatin and its metabolite simvastatin acid in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(11): 1242-1249.
[14]	DONG Jinliang. Effects of weekly liposome paclitaxel combined with tiggio on serum tumor markers and soluble e-cadherin in elderly patients with advanced gastric cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 805-809.
[15]	XUE Hua, LU Lili, XIANG Hui, QIAN Zhenhua. Curative efficacy of ulinastatin combined with hydrocortisone in treatment of severe sepsis secondary shock and effects on serum factor levels [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 313-317.