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Published in: Drugs & Aging 3/2020

01-03-2020 | Diseases of the neuromuscular synapses and muscles | Systematic Review

The Safety and Tolerability of Statin Therapy in Primary Prevention in Older Adults: A Systematic Review and Meta-analysis

Authors: Zhen Zhou, Loai Albarqouni, Andrea J. Curtis, Monique Breslin, Mark Nelson

Published in: Drugs & Aging | Issue 3/2020

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Abstract

Purpose

The use of statins in the primary prevention of cardiovascular disease (CVD) is increasing in older adults. Nonetheless, good clinical evidence for the safety and tolerability of statins in this population is limited.

Objective

We aimed to evaluate the safety and tolerability of statins in older adults without overt CVD, focusing on statin-related muscle symptoms.

Methods

Double-blinded randomised controlled trials (RCTs) of statins published before January 2012 were identified from a Cochrane review updated to 2012. Trials published between January 2012 and July 2018 were identified through the CENTRAL, MEDLINE and EMBASE databases. Eligible trials were limited to those including individuals aged ≥ 65 years without overt CVD, who were followed for at least 1 year. Trials had to have reported at least one of the outcomes of interest. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects models.

Results

We identified 11 trials, including 18,192 participants (mean age 73.7 years; 43% females). Compared with placebo, statins neither increased the risks of muscle-related symptoms (RR 1.01; 95% CI 0.90–1.12), total adverse events (AEs) and serious AEs nor led to more total permanent treatment discontinuations and discontinuations due to AEs or specifically due to muscle-related symptoms. No evidence of heterogeneity was observed in any of these outcomes.

Conclusions

This meta-analysis of RCTs found no excess incidence of muscle-related symptoms, total AEs, serious AEs and treatment discontinuations attributable to statin treatment compared with placebo among older adults without CVD.
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Literature
1.
go back to reference Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168–209.CrossRef Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168–209.CrossRef
2.
go back to reference Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71(1):85–94.CrossRef Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71(1):85–94.CrossRef
3.
go back to reference Hawley CE, Roefaro J, Forman DE, Orkaby AR. Statins for primary prevention in those aged 70 years and older: a critical review of recent cholesterol guidelines. Drugs Aging. 2019;36(8):687–99.CrossRef Hawley CE, Roefaro J, Forman DE, Orkaby AR. Statins for primary prevention in those aged 70 years and older: a critical review of recent cholesterol guidelines. Drugs Aging. 2019;36(8):687–99.CrossRef
4.
go back to reference Mortensen MB, Falk E, Schmidt M. Twenty-year nationwide trends in statin utilization and expenditure in Denmark. Circ Cardiovasc Qual Outcomes. 2017;10(7). Mortensen MB, Falk E, Schmidt M. Twenty-year nationwide trends in statin utilization and expenditure in Denmark. Circ Cardiovasc Qual Outcomes. 2017;10(7).
5.
go back to reference Ofori-Asenso R, Ilomaki J, Zomer E, Curtis AJ, Zoungas S, Liew D. A 10-year trend in statin use among older adults in Australia: an analysis using national pharmacy claims data. Cardiovasc Drugs Ther. 2018;32(3):265–72.CrossRef Ofori-Asenso R, Ilomaki J, Zomer E, Curtis AJ, Zoungas S, Liew D. A 10-year trend in statin use among older adults in Australia: an analysis using national pharmacy claims data. Cardiovasc Drugs Ther. 2018;32(3):265–72.CrossRef
6.
go back to reference Salami JA, Warraich H, Valero-Elizondo J, Spatz ES, Desai NR, Rana JS, et al. National trends in statin use and expenditures in the US Adult Population From 2002 to 2013: insights From the medical expenditure panel survey. JAMA Cardiol. 2017;2(1):56–65.CrossRef Salami JA, Warraich H, Valero-Elizondo J, Spatz ES, Desai NR, Rana JS, et al. National trends in statin use and expenditures in the US Adult Population From 2002 to 2013: insights From the medical expenditure panel survey. JAMA Cardiol. 2017;2(1):56–65.CrossRef
7.
go back to reference Gurwitz JH, Go AS, Fortmann SP. Statins for primary prevention in older adults: uncertainty and the need for more evidence. JAMA. 2016;316(19):1971–2.CrossRef Gurwitz JH, Go AS, Fortmann SP. Statins for primary prevention in older adults: uncertainty and the need for more evidence. JAMA. 2016;316(19):1971–2.CrossRef
8.
go back to reference Golomb BA. Implications of statin adverse effects in the elderly. Expert Opin Drug Saf. 2005;4(3):389–97.CrossRef Golomb BA. Implications of statin adverse effects in the elderly. Expert Opin Drug Saf. 2005;4(3):389–97.CrossRef
9.
go back to reference Bellosta S, Corsini A. Statin drug interactions and related adverse reactions: an update. Expert Opin Drug Saf. 2018;17(1):25–37.CrossRef Bellosta S, Corsini A. Statin drug interactions and related adverse reactions: an update. Expert Opin Drug Saf. 2018;17(1):25–37.CrossRef
10.
go back to reference Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy-European atherosclerosis society consensus panel statement on assessment. Aetiol Manag Eur Heart J. 2015;36(17):1012–22.CrossRef Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy-European atherosclerosis society consensus panel statement on assessment. Aetiol Manag Eur Heart J. 2015;36(17):1012–22.CrossRef
11.
go back to reference Curfman G. Risks of statin therapy in older adults. JAMA Intern Med. 2017;177(7):966.CrossRef Curfman G. Risks of statin therapy in older adults. JAMA Intern Med. 2017;177(7):966.CrossRef
12.
go back to reference Valiyil R, Christopher-Stine L. Drug-related myopathies of which the clinician should be aware. Curr Rheumatol Rep. 2010;12(3):213–20.CrossRef Valiyil R, Christopher-Stine L. Drug-related myopathies of which the clinician should be aware. Curr Rheumatol Rep. 2010;12(3):213–20.CrossRef
13.
go back to reference Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.CrossRef Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.CrossRef
14.
go back to reference Zhou Z, Albarqouni L, Breslin M, Curtis AJ, Nelson M. Statin-associated muscle symptoms (SAMS) in primary prevention for cardiovascular disease in older adults: a protocol for a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2017;7(9):e017587.CrossRef Zhou Z, Albarqouni L, Breslin M, Curtis AJ, Nelson M. Statin-associated muscle symptoms (SAMS) in primary prevention for cardiovascular disease in older adults: a protocol for a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2017;7(9):e017587.CrossRef
15.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRef Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRef
16.
go back to reference Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816.
17.
go back to reference Grundy SM. Can statins cause chronic low-grade myopathy? Ann Intern Med. 2002;137(7):617–8.CrossRef Grundy SM. Can statins cause chronic low-grade myopathy? Ann Intern Med. 2002;137(7):617–8.CrossRef
19.
go back to reference Higgins J GS. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane collaboration. 2011. Higgins J GS. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane collaboration. 2011.
20.
go back to reference Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.
22.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.CrossRef
23.
go back to reference Wang J, Chen D, Li DB, Yu X, Shi GB. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: a meta-analysis. Medicine (Baltimore). 2016;95(39):e4950.CrossRef Wang J, Chen D, Li DB, Yu X, Shi GB. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: a meta-analysis. Medicine (Baltimore). 2016;95(39):e4950.CrossRef
24.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRef Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRef
25.
go back to reference Higgins JP, Thompson SG. Controlling the risk of spurious findings from meta-regression. Stat Med. 2004;23(11):1663–82.CrossRef Higgins JP, Thompson SG. Controlling the risk of spurious findings from meta-regression. Stat Med. 2004;23(11):1663–82.CrossRef
26.
go back to reference Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–31.CrossRef Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–31.CrossRef
27.
go back to reference Yusuf S, Lonn E, Pais P, Bosch J, Lopez-Jaramillo P, Zhu J, et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med. 2016;374(21):2032–43.CrossRef Yusuf S, Lonn E, Pais P, Bosch J, Lopez-Jaramillo P, Zhu J, et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med. 2016;374(21):2032–43.CrossRef
28.
go back to reference Group MBHPSC, Armitage J, Bowman L, Collins R, Parish S, Tobert J. Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people. BMC Clin Pharmacol. 2009;9:6. Group MBHPSC, Armitage J, Bowman L, Collins R, Parish S, Tobert J. Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people. BMC Clin Pharmacol. 2009;9:6.
29.
go back to reference Furberg CD, Adams HP, Jr., Applegate WB, Byington RP, Espeland MA, Hartwell T, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation. 1994;90(4):1679–87. Furberg CD, Adams HP, Jr., Applegate WB, Byington RP, Espeland MA, Hartwell T, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation. 1994;90(4):1679–87.
30.
go back to reference Bruckert E, Lievre M, Giral P, Crepaldi G, Masana L, Vrolix M, et al. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients. Am J Geriatr Cardiol. 2003;12(4):225–31.CrossRef Bruckert E, Lievre M, Giral P, Crepaldi G, Masana L, Vrolix M, et al. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients. Am J Geriatr Cardiol. 2003;12(4):225–31.CrossRef
31.
go back to reference Chan P, Tomlinson B, Lee CB, Pan WH, Lee YS. Beneficial effects of pravastatin on fasting hyperinsulinemia in elderly hypertensive hypercholesterolemic subjects. Hypertension. 1996;28(4):647–51.CrossRef Chan P, Tomlinson B, Lee CB, Pan WH, Lee YS. Beneficial effects of pravastatin on fasting hyperinsulinemia in elderly hypertensive hypercholesterolemic subjects. Hypertension. 1996;28(4):647–51.CrossRef
32.
go back to reference Collier DJ, Poulter NR, Dahlof B, Sever PS, Wedel H, Buch J, et al. Impact of atorvastatin among older and younger patients in the Anglo-Scandinavian cardiac outcomes trial lipid-lowering arm. J Hypertens. 2011;29(3):592–9.CrossRef Collier DJ, Poulter NR, Dahlof B, Sever PS, Wedel H, Buch J, et al. Impact of atorvastatin among older and younger patients in the Anglo-Scandinavian cardiac outcomes trial lipid-lowering arm. J Hypertens. 2011;29(3):592–9.CrossRef
33.
go back to reference Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.CrossRef Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.CrossRef
34.
go back to reference Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–96.CrossRef Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–96.CrossRef
35.
go back to reference Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O’Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297(12):1344–53.CrossRef Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O’Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297(12):1344–53.CrossRef
36.
go back to reference Bone HG, Kiel DP, Lindsay RS, Lewiecki EM, Bolognese MA, Leary ET, et al. Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab. 2007;92(12):4671–7.CrossRef Bone HG, Kiel DP, Lindsay RS, Lewiecki EM, Bolognese MA, Leary ET, et al. Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab. 2007;92(12):4671–7.CrossRef
37.
go back to reference Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110(18):2809–16.CrossRef Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110(18):2809–16.CrossRef
38.
go back to reference Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29(7):1478–85.CrossRef Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29(7):1478–85.CrossRef
39.
go back to reference Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–30.CrossRef Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–30.CrossRef
40.
go back to reference Teng M, Lin L, Zhao YJ, Khoo AL, Davis BR, Yong QW, et al. Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis. Drugs Aging. 2015;32(8):649–61.CrossRef Teng M, Lin L, Zhao YJ, Khoo AL, Davis BR, Yong QW, et al. Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis. Drugs Aging. 2015;32(8):649–61.CrossRef
41.
go back to reference Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–22. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–22.
42.
go back to reference Iwere RB, Hewitt J. Myopathy in older people receiving statin therapy: a systematic review and meta-analysis. Br J Clin Pharmacol. 2015;80(3):363–71.CrossRef Iwere RB, Hewitt J. Myopathy in older people receiving statin therapy: a systematic review and meta-analysis. Br J Clin Pharmacol. 2015;80(3):363–71.CrossRef
43.
go back to reference Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, 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 randomised controlled trial. Lancet. 2003;361(9364):1149–58.CrossRef Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, 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 randomised controlled trial. Lancet. 2003;361(9364):1149–58.CrossRef
44.
go back to reference Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. 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. Ann Intern Med. 2010;152(8):488–96 (W174). Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. 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. Ann Intern Med. 2010;152(8):488–96 (W174).
45.
go back to reference Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–410.CrossRef Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–410.CrossRef
46.
go back to reference Ofori-Asenso R, Ilomaki J, Tacey M, Si S, Curtis AJ, Zomer E, et al. Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study. Br J Clin Pharmacol. 2019;85(1):227–35.CrossRef Ofori-Asenso R, Ilomaki J, Tacey M, Si S, Curtis AJ, Zomer E, et al. Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study. Br J Clin Pharmacol. 2019;85(1):227–35.CrossRef
47.
go back to reference Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158(7):526–34.CrossRef Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158(7):526–34.CrossRef
48.
go back to reference Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389(10088):2473–81.CrossRef Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389(10088):2473–81.CrossRef
49.
go back to reference Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific medication side effects and the nocebo phenomenon. JAMA. 2002;287(5):622–7.CrossRef Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific medication side effects and the nocebo phenomenon. JAMA. 2002;287(5):622–7.CrossRef
50.
go back to reference Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: mechanisms and management. Diabetes Care. 2013;36(Suppl 2):S325–30.CrossRef Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: mechanisms and management. Diabetes Care. 2013;36(Suppl 2):S325–30.CrossRef
Metadata
Title
The Safety and Tolerability of Statin Therapy in Primary Prevention in Older Adults: A Systematic Review and Meta-analysis
Authors
Zhen Zhou
Loai Albarqouni
Andrea J. Curtis
Monique Breslin
Mark Nelson
Publication date
01-03-2020
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 3/2020
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-019-00736-y

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