{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:13:03Z","timestamp":1790957583766,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Our objective was to estimate the comparative harms of individual statins using both placebo-controlled and active-comparator trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>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\u2009955 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\u20131.16) and transaminase elevations (odds ratio, 1.51; 95% confidence interval, 1.24\u20131.84) 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\u201316.24). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circoutcomes.111.000071","type":"journal-article","created":{"date-parts":[[2013,7,10]],"date-time":"2013-07-10T00:52:19Z","timestamp":1373417539000},"page":"390-399","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":248,"title":["Comparative Tolerability and Harms of Individual Statins"],"prefix":"10.1161","volume":"6","author":[{"given":"Huseyin","family":"Naci","sequence":"first","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Brugts","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Ades","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67394-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60104-X"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60367-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2376"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.063"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.09.067"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.11.013"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60694-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.12.010"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00705-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.06.025"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.1.74"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0738"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61965-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-007-6040-4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e32825a6773"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.01.005"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.02.008"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(03)00820-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.08.014"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcr158"},{"key":"e_1_3_3_24_2","unstructured":"Naci H Brugts J Fleurence R Ades AE. Comparative efficacy and safety of statins: a systematic review and mixed treatment comparison\u2014final protocol. 2009; www2.lse.ac.uk\/LSEHealthAndSocialCare\/pdf\/HNaciProtocol.pdf. Accessed April 5 2013."},{"key":"e_1_3_3_25_2","unstructured":"Higgins JPT Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. www.cochrane-handbook.org.2011. Accessed April 5 2013."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7521.897"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1201"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1875"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","unstructured":"Dias S Welton NJ Sutton AJ Ades AE. NICE DSU technical support document 1: introduction to evidence synthesis for decision making\u2014report by the decision support unit. 2011; http:\/\/www.nicedsu.org.uk. Accessed April 5 2013.","DOI":"10.1177\/0272989X13487604"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.12"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.03.016"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3594"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.465"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.423"},{"issue":"1","key":"e_1_3_3_35_2","article-title":"Statins for the primary prevention of cardiovascular disease.","author":"Taylor F","year":"2011","unstructured":"Taylor F, Ward K, Moore Theresa HM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev[serial on the Internet]. 2011;1: http:\/\/www.mrw.interscience.wiley.com\/cochrane\/clsysrev\/articles\/CD004816\/frame.html. Accessed April 5, 2013.","journal-title":"Cochrane Database Syst Rev"},{"issue":"9326","key":"e_1_3_3_36_2","article-title":"MRC\/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.","author":"Heart Protection Study Collaborative G","year":"2002","unstructured":"Heart Protection Study Collaborative G. MRC\/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet [serial on the Internet]. 2002;9326: http:\/\/www.mrw.interscience.wiley.com\/cochrane\/clcentral\/articles\/225\/CN-00390225\/frame.html. Accessed April 5, 2013.","journal-title":"Lancet"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.624890"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.78a.10073"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.08.022"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-12-200906160-00009"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61190-8"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001361"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)03190-6"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1C116"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487313480435"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487313483600"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hct041"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.01.067"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.860"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.02.073"}],"container-title":["Circulation: Cardiovascular Quality and Outcomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCOUTCOMES.111.000071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:44:29Z","timestamp":1715553869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCOUTCOMES.111.000071"}},"subtitle":["A Study-Level Network Meta-Analysis of 246 955 Participants From 135 Randomized, Controlled Trials"],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1161\/CIRCOUTCOMES.111.000071"],"URL":"https:\/\/doi.org\/10.1161\/circoutcomes.111.000071","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718140503.793485129","asserted-by":"object"}]},"ISSN":["1941-7713","1941-7705"],"issn-type":[{"value":"1941-7713","type":"print"},{"value":"1941-7705","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7]]},"assertion":[{"value":"2013-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}