The DOI matches its Crossref record, with a small difference in title or year; 50 of the 52 references it cites were found in a registry or an index.
Comparative Tolerability and Harms of Individual Statins: A Study-Level Network Meta-Analysis of 246 955 Participants From 135 Randomized, Controlled Trials
Open accessAbstract
Background—: Our objective was to estimate the comparative harms of individual statins using both placebo-controlled and active-comparator trials. Methods and Results—: We systematically reviewed randomized trials evaluating different statins in participants with and without cardiovascular disease. We performed random-effects pairwise and network meta-analyses to quantify the relative harms of individual statins. We included 55 two-armed placebo-controlled and 80 two- or multiarmed active-comparator trials including 246 955 individuals. According to pairwise meta-analyses, individual statins were not different than control in terms of myalgia, creatine kinase elevation, cancer, and discontinuations because of adverse events. Statins as a class resulted in significantly higher odds of diabetes mellitus (odds ratio, 1.09; 95% confidence interval, 1.02–1.16) and transaminase elevations (odds ratio, 1.51; 95% confidence interval, 1.24–1.84) compared with control. When individual statins were compared in network meta-analyses, there were numerous statistically detectable differences, favoring simvastatin and pravastatin. According to dose-level comparisons, individual statins resulted in higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin. Similarly, higher doses of atorvasatin, fluvastatin, lovastatin, and simvastatin were associated with higher odds of transaminase elevations. Simvastatin at its highest doses was associated with creatine kinase elevations (odds ratio, 4.14; 95% credible interval, 1.08–16.24). Meta-regression analyses adjusting for study-level age at baseline, low-density lipoprotein cholesterol level, and publication year did not explain heterogeneity. There was no detectable inconsistency in the network. Conclusions—: As a class, adverse events associated with statin therapy are not common. Statins are not associated with cancer risk but do result in a higher odds of diabetes mellitus. Among individual statins, simvastatin and pravastatin seem safer and more tolerable than other statins.
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In the citing paper
“In one study the baseline scores varied by almost 25% [24] and by 5-10% in two others [6,11].”
From Effect of Coenzyme Q10 on statin-associated myalgia and adherence to statin therapy: A systematic review and meta-analysis (2020) · cites this paper as [24]
Experimental — accuracy not yet measuredIn the citing paper
“Other conditions, such as dementia [224], hepatic steatosis [225], venous thromboembolism [226], atrial fibrillation [227,228], and polycystic ovary syndrome [229] have also been studied, and no effect of statins on these conditions has been reliably demonstrated.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [224]
In the citing paper
“In meta-analyses of RCTs, no increased frequency in statin-treated groups has been shown. 213,214”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [214]
In the citing paper
“In meta-analyses of RCTs, no increased frequency in statin-treated groups has been shown.213,214”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [214]
In the citing paper
“A systematic review found that the incidence of drug-induced hepatotoxicity in patients taking statins is unknown, with very few cases occurring in large-scale RCTs.212,214”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [214]
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A basic introduction to fixed-effect and random-effects models for meta-analysis
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2010) · Research Synthesis Methods · doi:10.1002/jrsm.12 · Cited by 6,793
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The Cochrane Collaboration
Higgins, J., Green, S. R., & Higgins, J. (2008) · Cited by 5,544
Salanti, G., Ades, A. E., & Ioannidis, J. P. A. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.03.016 · Cited by 3,766
Collaborators, C. T. T. (. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60367-5 · Cited by 2,833
Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials
Sattar, N., Preiss, D., Murray, H. M., Welsh, P., Buckley, B. M., de Craen, A. J., Seshasai, S. R. K., McMurray, J. J., Freeman, D. J., Jukema, J. W., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61965-6 · Cited by 2,436
Combination of direct and indirect evidence in mixed treatment comparisons
Lu, G., & Ades, A. E. (2004) · Statistics in Medicine · doi:10.1002/sim.1875 · Cited by 2,172
Collaborators, C. T. T. (. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60104-x · Cited by 2,081
Research works printed but not linked: 1
- Naci H Brugts J Fleurence R Ades AE. Comparative efficacy and safety of statins: a systematic review and mixed treatment comparison—final protocol. 2009; www2.lse.ac.uk/LSEHealthAndSocialCare/pdf/HNaciProtocol.pdf. Accessed April 5 2013.
Cited by
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Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw272 · Cited by 3,162
CINeMA: an approach for assessing confidence in the results of a network meta-analysis
Nikolakopoulou, A., Higgins, J. P. T., Papakonstantinou, T., Chaimani, A., Del Giovane, C., Egger, M., & Salanti, G. (2020) · PLOS Medicine · doi:10.1371/journal.pmed.1003082 · Cited by 1,935
Interpretation of the evidence for the efficacy and safety of statin therapy
Collins, R., Reith, C., Emberson, J., Armitage, J., Baigent, C., Blackwell, L., Blumenthal, R., Danesh, J., Smith, G. D., DeMets, D., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31357-5 · Cited by 1,857
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.018 · Cited by 1,582
Metadata
- Authors
- Naci, H., Brugts, J., & Ades, T.
- Affiliations
- Erasmus MC (NL)
- From the LSE Health, London School of Economics and Political Science, London, United Kingdom (H.N.); Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands (J.B.); and .School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom (T.A.).
- Venue
- Circulation: Cardiovascular Quality and Outcomes
- Published
- 2013-07
- Volume
- 6
- Issue
- 4
- Pages
- 390-399
- ISSN
- 1941-7705 (ISSN-L)
- 1941-7713
- OpenAlex
- W2160313369
- Cited by
- 292
- References
- 52
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 17 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 26 · 2019: 31 · 2018: 23 · 2017: 21 · 2016: 36 · 2015: 24 · 2014: 38 · 2013: 8
- FWCI
- 34.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Cardiovascular Quality and Outcomes (publishedVersion)
- PubMed (publishedVersion)
- London School of Economics and Political Science Research Online (London School of Economics and Political Science) (acceptedVersion)
- London School of Economics and Political Science Research Online (London School of Economics and Political Science) (submittedVersion)
- Funders
- McMaster University
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- statins, statin safety, tolerability, diabetes mellitus, transaminase elevation, creatine kinase elevation, myalgia, cancer risk, simvastatin, pravastatin, dose-response relationship, cardiovascular disease
- MeSH terms
- Cardiovascular Diseases, Dose-Response Relationship, Drug, Humans, Lipids, Risk Factors, Biomarkers, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Evidence-Based Medicine, Dyslipidemias
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