Preventive cardiology for the aging population: how can we better design clinical trials of statins?

References

• Cracknell R. The ageing population. In: key issues for the new parliament 2010. London (UK): House of Commons Library Research, 2010: p. 44.
   Google Scholar
• Christensen K, Doblhammer G, Rau R, et al. Ageing populations: the challenges ahead. Lancet. 2009;374(9696):1196–1208. doi: 10.1016/S0140-6736(09)61460-4
   PubMed Web of Science ®Google Scholar
• Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88(9):1337–1342. doi: 10.2105/AJPH.88.9.1337
   PubMed Web of Science ®Google Scholar
• Pencina MJ, Navar AM, Wojdyla D, et al. Quantifying importance of major risk factors for coronary heart disease. Circulation. 2019;139(13):1603–1611. doi: 10.1161/CIRCULATIONAHA.117.031855
   PubMed Web of Science ®Google Scholar
• Kaneko H, Yano Y, Okada A, et al. Age-dependent association between modifiable risk factors and incident cardiovascular disease. J Am Heart Assoc. 2023;12(2):e027684. doi: 10.1161/JAHA.122.027684
   PubMed Web of Science ®Google Scholar
• Dumurgier J, Singh-Manoux A, Tavernier B, et al. Lipid-lowering drugs associated with slower motor decline in the elderly adults. J Gerontol Ser A. 2014;69(2):199–206. doi: 10.1093/gerona/glt140
   PubMed Web of Science ®Google Scholar
• Wong WB, Lin VW, Boudreau D, et al. Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22(4):345–358. doi: 10.1002/pds.3381
   PubMed Web of Science ®Google Scholar
• Undela K, Gudala K, Malla S, et al. Statin use and risk of Parkinson’s disease: a meta-analysis of observational studies. J Neurol. 2013;260(1):158–165. doi: 10.1007/s00415-012-6606-3
   PubMed Web of Science ®Google Scholar
• Macedo AF, Taylor FC, Casas JP, et al. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med. 2014;12(1):51. doi: 10.1186/1741-7015-12-51
   PubMedGoogle Scholar
• Martin SS, Niles JK, Kaufman HW, et al. Lipid distributions in the global diagnostics network across five continents. Eur Heart J. 2023;44(25):2305–2318. doi: 10.1093/eurheartj/ehad371
   PubMed Web of Science ®Google Scholar
• Zhong S, Zhang X, Chen L, et al. Statin use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Cancer Treat Rev. 2015;41(6):554–567. doi: 10.1016/j.ctrv.2015.04.005
   PubMed Web of Science ®Google Scholar
• Collaborators CTTC, Emberson J, Kearney P, et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One. 2012;7(1):e29849. doi: 10.1371/journal.pone.0029849
   PubMed Web of Science ®Google Scholar
• Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation. 2013;6(4):390–399. doi: 10.1161/CIRCOUTCOMES.111.000071
   PubMed Web of Science ®Google Scholar
• Mancini GB, Tashakkor AY, Baker S, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian working group consensus update. Can J Cardiol. 2013;29(12):1553–1568. doi: 10.1016/j.cjca.2013.09.023
   PubMed Web of Science ®Google Scholar
• Ruscica M, Ferri N, Banach M, et al. Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications. Cardiovasc Res. 2023;44(25–17):3288–3304. doi: 10.1093/cvr/cvac020
   Google Scholar
• Andersson NW, Corn G, Dohlmann TL, et al. LDL-C reduction with lipid-lowering therapy for primary prevention of major vascular events among older individuals. J Am Coll Cardiol. 2023;82(14):1381–1391. doi:10.1016/j.jacc.2023.07.027
   PubMed Web of Science ®Google Scholar
• Corn G, Melbye M, Hlatky MA, et al. Association between age and low-density lipoprotein cholesterol response to statins: a Danish nationwide cohort study. Ann Intern Med. 2023;176(8):1017–1026. doi: 10.7326/M22-2643
   PubMed Web of Science ®Google Scholar
• Bergami M, Cenko E, Yoon J, et al. Statins for primary prevention among elderly men and women. Cardiovasc Res. 2022;118(14):3000–3009. doi: 10.1093/cvr/cvab348
   PubMed Web of Science ®Google Scholar
• Cho Y, Jeong Y, Seo DH, et al. Use of statin for the primary prevention of cardiovascular outcomes in elderly patients: a propensity-matched cohort study. Atherosclerosis. 2021;328:92–99. doi: 10.1016/j.atherosclerosis.2021.05.022
   PubMed Web of Science ®Google Scholar
• Ramos R, Comas-Cufi M, Marti-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. BMJ. 2018;362:k3359. doi: 10.1136/bmj.k3359
   PubMedGoogle Scholar
• Veronese N. Frailty as Cardiovascular Risk Factor (and Vice Versa). Adv Exp Med Biol. 2020;1216:51–54.
   PubMed Web of Science ®Google Scholar
• Stewart R. Cardiovascular disease and frailty: what are the mechanistic links? Clin Chem. 2019;65(1):80–86. doi: 10.1373/clinchem.2018.287318
   PubMed Web of Science ®Google Scholar
• Gulliford M, Ravindrarajah R, Hamada S, et al. Inception and deprescribing of statins in people aged over 80 years: cohort study. Age Ageing. 2017;46(6):1001–1005. doi: 10.1093/ageing/afx100
   PubMed Web of Science ®Google Scholar
• Brugts J, Yetgin T, Hoeks S, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338(jun30 1):b2376. doi: 10.1136/bmj.b2376
   PubMedGoogle Scholar
• Strandberg TE. Role of statin therapy in primary prevention of cardiovascular disease in elderly patients. Curr Atheroscler Rep. 2019;21(8):28. doi: 10.1007/s11883-019-0793-7
   PubMed Web of Science ®Google Scholar
• Bytyci I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;43(34):3213–3223. doi: 10.1093/eurheartj/ehac015
   PubMed Web of Science ®Google Scholar
• Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887–1898. doi: 10.1056/NEJMoa0801369
   PubMed Web of Science ®Google Scholar
• McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379(16):1509–1518. doi: 10.1056/NEJMoa1805819
   PubMed Web of Science ®Google Scholar
• McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 2018;379(16):1499–1508. doi: 10.1056/NEJMoa1800722
   PubMed Web of Science ®Google Scholar
• McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379(16):1519–1528. doi: 10.1056/NEJMoa1803955
   PubMed Web of Science ®Google Scholar
• Cloud GC, Williamson JD, Thao LTP, et al. Low-dose aspirin and the risk of stroke and intracerebral bleeding in healthy older people: secondary analysis of a randomized clinical trial. JAMA Netw Open. 2023;6(7):e2325803. doi: 10.1001/jamanetworkopen.2023.25803
   PubMed Web of Science ®Google Scholar
• Ryan J, Storey E, Murray AM, et al. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology. 2020;95(3):e320–e331. doi: 10.1212/WNL.0000000000009277
   PubMed Web of Science ®Google Scholar
• Ford I, Blauw G, Murphy MB, et al. A prospective study of pravastatin in the elderly at risk (PROSPER): screening experience and baseline characteristics. Curr Control Trials Cardiovasc Med. 2002;3(1):8. doi: 10.1186/1468-6708-3-8
   PubMedGoogle Scholar
• Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–1630. doi: 10.1016/S0140-6736(02)11600-X
   PubMed Web of Science ®Google Scholar
• Han BH, Sutin D, Williamson JD, et al. 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. doi: 10.1001/jamainternmed.2017.1442
   PubMed Web of Science ®Google Scholar
• The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Investigators. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT). JAMA. 2002;288(23):2998–3007. doi: 10.1001/jama.288.23.2998
   PubMed Web of Science ®Google Scholar
• 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. Circulation. 2017;135(20):1979–1981. doi: 10.1161/CIRCULATIONAHA.117.028271
   PubMed Web of Science ®Google Scholar
• Lee SH, Lee YJ, Heo JH, et al. Combination moderate-intensity statin and ezetimibe therapy for elderly patients with atherosclerosis. J Am Coll Cardiol. 2023;81(14):1339–1349. doi: 10.1016/j.jacc.2023.02.007
   PubMed Web of Science ®Google Scholar
• Ouchi Y, Sasaki J, Arai H, et al. Ezetimibe lipid-lowering trial on prevention of atherosclerotic cardiovascular disease in 75 or older (EWTOPIA 75): a randomized, controlled trial. Circulation. 2019;140(12):992–1003. doi: 10.1161/CIRCULATIONAHA.118.039415
   PubMed Web of Science ®Google Scholar
• Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396(10263):1637–1643. doi: 10.1016/S0140-6736(20)32332-1
   PubMed Web of Science ®Google Scholar
• 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. Lancet. 2019;393(10170):407–415. doi: 10.1016/S0140-6736(18)31942-1
   PubMed Web of Science ®Google Scholar
• Kostis JB, Giakoumis M, Zinonos S, et al. Meta-analysis of usefulness of treatment of hypercholesterolemia with statins for primary prevention in patients older than 75 years. Am J Cardiol. 2020;125(8):1154–1157. doi: 10.1016/j.amjcard.2020.01.020
   PubMed Web of Science ®Google Scholar
• Hawley CE, Roefaro J, Forman DE, et al. Statins for primary prevention in those aged 70 years and older: a critical review of recent cholesterol guidelines. Drugs Aging. 2019;36(8):687–699. doi: 10.1007/s40266-019-00673-w
   PubMed Web of Science ®Google Scholar
• Ruscica M, Macchi C, Pavanello C, et al. Appropriateness of statin prescription in the elderly. Eur J Intern Med. 2018;50:33–40. doi: 10.1016/j.ejim.2017.12.011
   PubMed Web of Science ®Google Scholar
• Zoungas S, Curtis A, Spark S, et al. Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial). BMJ Open. 2023;13(4):e069915. doi: 10.1136/bmjopen-2022-069915
   PubMed Web of Science ®Google Scholar
• Joseph J, Pajewski NM, Dolor RJ, et al. Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): trial design and rationale. J Am Geriatr Soc. 2023;71(6):1701–1713. doi: 10.1111/jgs.18312
   PubMed Web of Science ®Google Scholar
• Iughetti L, Bruzzi P, Predieri B. Evaluation and management of hyperlipidemia in children and adolescents. Curr Opin Pediatr. 2010;22(4):485–493. doi: 10.1097/MOP.0b013e32833ab869
   PubMed Web of Science ®Google Scholar
• Tinetti M, Huang A, Molnar F. The geriatrics 5M’s: a new way of communicating what we do. J Am Geriatr Soc. 2017;65(9):2115. doi: 10.1111/jgs.14979
   PubMed Web of Science ®Google Scholar
• Hu X, Mok Y, Ding N, et al. Physical function and subsequent risk of cardiovascular events in older adults: the atherosclerosis risk in communities study. J Am Heart Assoc. 2022;11(17):e025780. doi: 10.1161/JAHA.121.025780
   PubMed Web of Science ®Google Scholar
• Wang F, Rozanski A, Dey D, et al. Age- and gender-adjusted percentiles for number of calcified plaques in coronary artery calcium scanning. J Cardiovasc Comput Tomogr. 2019;13(6):319–324. doi: 10.1016/j.jcct.2018.12.001
   PubMed Web of Science ®Google Scholar
• Kleipool EE, Dorresteijn JA, Smulders YM, et al. Treatment of hypercholesterolaemia in older adults calls for a patient-centred approach. Heart. 2020;106(4):261–266. doi: 10.1136/heartjnl-2019-315600
   PubMed Web of Science ®Google Scholar