The Safety and Tolerability of Statin Therapy in Primary Prevention in Older Adults: A Systematic Review and Meta-analysis
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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.
We aimed to evaluate the safety and tolerability of statins in older adults without overt CVD, focusing on statin-related muscle symptoms.
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.
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.
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.
The authors thank Dr. Frank Brouwers for providing unpublished individual patient data from PREVEND IT, AstraZeneca for providing the data from the METEOR trial and Pfizer for providing the data from the BONE and ASPEN trials.
Compliance with Ethical Standards
No sources of funding were used to conduct this study or prepare this manuscript.
Conflict of interest
MN has participated on an advisory board for Amgen, who make a lipid-lowering agent. ZZ, LA, AC and MB have no conflicts of interest that are directly relevant to the content of this article.
Not applicable for this meta-analysis.
- 1.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.PubMedCrossRefPubMedCentralGoogle Scholar
- 4.Mortensen MB, Falk E, Schmidt M. Twenty-year nationwide trends in statin utilization and expenditure in Denmark. Circ Cardiovasc Qual Outcomes. 2017;10(7).Google Scholar
- 14.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.PubMedPubMedCentralCrossRefGoogle Scholar
- 16.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.Google Scholar
- 18.Definitions http://www.who.int/medicines/areas/quality_safety/safety_efficacy/trainingcourses/definitions.pdf. World Health Organisation. Accessed 15 Jan 2019.
- 19.Higgins J GS. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane collaboration. 2011.Google Scholar
- 21.Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. http://handbook-5-1.cochrane.org. The Cochrane collaboration. Accessed 15 Jan 2019.
- 28.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.Google Scholar
- 29.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.PubMedCrossRefPubMedCentralGoogle Scholar
- 34.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.PubMedCrossRefPubMedCentralGoogle Scholar
- 38.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.PubMedCrossRefPubMedCentralGoogle Scholar
- 41.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.Google Scholar
- 43.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.PubMedCrossRefPubMedCentralGoogle Scholar
- 44.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).PubMedPubMedCentralCrossRefGoogle Scholar
- 48.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.PubMedCrossRefPubMedCentralGoogle Scholar