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Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials.

Abstract

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.

Authors+Show Affiliations

LSE Health, London School of Economics and Political Science, London, United Kingdom. h.naci@lse.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

23838105

Citation

Naci, Huseyin, et al. "Comparative Tolerability and Harms of Individual Statins: a Study-level Network Meta-analysis of 246 955 Participants From 135 Randomized, Controlled Trials." Circulation. Cardiovascular Quality and Outcomes, vol. 6, no. 4, 2013, pp. 390-9.
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. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-9.
Naci, H., Brugts, J., & Ades, T. (2013). Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation. Cardiovascular Quality and Outcomes, 6(4), pp. 390-9. doi:10.1161/CIRCOUTCOMES.111.000071.
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. Circ Cardiovasc Qual Outcomes. 2013;6(4):390-9. PubMed PMID: 23838105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. AU - Naci,Huseyin, AU - Brugts,Jasper, AU - Ades,Tony, Y1 - 2013/07/09/ PY - 2013/7/11/entrez PY - 2013/7/11/pubmed PY - 2014/3/13/medline KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - adverse effects KW - cardiovascular agents KW - cardiovascular disease KW - coronary disease KW - meta-analysis KW - statins SP - 390 EP - 9 JF - Circulation. Cardiovascular quality and outcomes JO - Circ Cardiovasc Qual Outcomes VL - 6 IS - 4 N2 - 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. SN - 1941-7705 UR - https://www.unboundmedicine.com/medline/citation/23838105/Comparative_tolerability_and_harms_of_individual_statins:_a_study_level_network_meta_analysis_of_246_955_participants_from_135_randomized_controlled_trials_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCOUTCOMES.111.000071?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -