{"id":8711,"date":"2011-06-12T23:53:41","date_gmt":"2011-06-13T03:53:41","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?p=8711"},"modified":"2011-07-19T17:45:17","modified_gmt":"2011-07-19T21:45:17","slug":"cardioexchange-panel-whither-high-dose-simvastatin","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2011\/06\/12\/cardioexchange-panel-whither-high-dose-simvastatin\/","title":{"rendered":"CardioExchange Panel: Whither High-Dose Simvastatin?"},"content":{"rendered":"

Last week, the FDA issued a warning high-dose simvastatin<\/a> because of the risk of myopathy.<\/em><\/p>\n

CardioExchange got the reactions from a panel we assembled. Whose views do you agree with? What points did our panelists miss?<\/strong><\/em><\/p>\n

See a similar panel’s reactions the publication of the SHARP Trial here<\/a>.<\/strong>
\n<\/strong><\/em><\/p>\n

Given the FDA warning, do you see any role for high-dose simvastatin?<\/em><\/span> <\/strong><\/p>\n

\"\"<\/a>Steven E. Nissen, MD<\/a><\/strong><\/p>\n

I wrote a JAMA editorial<\/a> about high-dose statins in ACS back in 2004. The FDA should have removed simvastatin 80 mg from the market years ago.<\/strong><\/p>\n

\"\"<\/a>Allen Taylor, MD<\/a><\/strong><\/p>\n

The FDA statement is consistent with a clinically-relevant safety difference that has been recognized for some time now- particularly important among the elderly with reduced renal function and those on certain concomitant therapies. Given numerous safe therapeutic alternatives for high potency statins, I believe simvastatin at the 80 mg\/d dose should be avoided. I disagree with the FDA statement from the perspective of whether patients currently taking the 80 mg dose should continue on that dose. I personally favor conversion of any patient taking the 80 mg dose to an alternative treatment approach (different statin or simvastatin dose reduction)<\/strong>, to avoid problems from interactions with future concomitant therapies, or changes in the rate of drug clearance.<\/p>\n

\"\"<\/a>Sanjay Kaul, MD<\/a><\/strong><\/p>\n

I stopped using high-dose simvastatin many years ago because of heightened risk of myopathy. <\/strong> I substitute 20-40 mg atorvastatin or 10-20 mg rosuvastatin for patients requiring greater than 40 mg simvastatin. In general, I am not a big fan of initiating high-dose statin therapy, even for patients with ACS. I like to start with low to intermediate statin dose and titrate up to optimize adherence. The adverse event rates related to statins is much higher in the real world practice compared with randomized trials where most patients intolerant to statins are filtered out during the active treatment “run-in” phase prior to randomization.<\/p>\n

The concerns have been seen in clinical trials since the A to Z study was published in JAMA<\/em> in 2004. At least 2 recent reports from the SEARCH study confirmed the risk. Also, simvastatin is cleared by cytochrome P 450 3A4, and many commonly used medications inhibit this pathway, so it is rather easy for patients on this high dose of simvastatin to develop “supra-therapeutic” blood levels of the drug. Of note, attempts at developing the 160 mg dose of simvastatin for clinical use were derailed because of muscle problems.<\/p>\n

\"\"<\/a> <\/strong>James H. Stein, MD<\/a><\/strong><\/p>\n

<\/strong>This is an especially important report because simvastatin is the most commonly used generic statin in the US and its rate of use still is rising. A lot of patients were put on 80 mg of simvastatin when it went generic or are put on it after MIs, and it, quite simply, is not as safe as high dose atorvastatin or rosuvastatin.<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

Last week, the FDA issued a warning high-dose simvastatin because of the risk of myopathy. CardioExchange got the reactions from a panel we assembled. Whose views do you agree with? What points did our panelists miss? See a similar panel’s reactions the publication of the SHARP Trial here. Given the FDA warning, do you see […]<\/p>\n","protected":false},"author":343,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,7],"tags":[196,868,665,534],"class_list":["post-8711","post","type-post","status-publish","format-standard","hentry","category-general","category-prevention","tag-fda","tag-myopathy","tag-primary-prevention","tag-simvastatin"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/8711","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/343"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=8711"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/8711\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=8711"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=8711"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=8711"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}