{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:03:45Z","timestamp":1762430625343},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T00:00:00Z","timestamp":1238457600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Clin Pharmacol"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Simvastatin reduces cardiovascular mortality and morbidity but, as with other HMG-CoA reductase inhibitors, can cause significant muscle toxicity and has been associated with elevations of liver transaminases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a randomized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes (in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The excess incidence of myopathy in the simvastatin group was &lt; 0.1% over the 5 years of the trial, and there were no significant differences between the treatment groups in the incidence of serious hepatobiliary disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Among the many different types of high-risk patient studied (including women, older individuals and those with low cholesterol levels), there was a very low incidence (&lt; 0.1%) of myopathy during 5 years treatment with simvastatin 40 mg daily. The risk of hepatitis, if any, was undetectable even in this very large long-term trial. Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial Registration<\/jats:title>\n            <jats:p>ISRCTN48489393<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1472-6904-9-6","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T08:47:15Z","timestamp":1336034835000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["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"],"prefix":"10.1186","volume":"9","author":[{"name":"MRC\/BHF Heart Protection Study Collaborative Group","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,3,31]]},"reference":[{"key":"68_CR1","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1517\/14656566.5.12.2583","volume":"5","author":"TR Pedersen","year":"2004","unstructured":"Pedersen TR, Tobert JA: Simvastatin: a review. 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