{"id":43271,"date":"2014-05-14T20:12:15","date_gmt":"2014-05-15T00:12:15","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=news&p=43271"},"modified":"2014-05-14T20:12:15","modified_gmt":"2014-05-15T00:12:15","slug":"bmj-articles-critical-of-statins-provoke-kerfuffle","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/05\/14\/bmj-articles-critical-of-statins-provoke-kerfuffle\/","title":{"rendered":"BMJ Articles Critical of Statins Provoke Kerfuffle"},"content":{"rendered":"

The authors of two\u00a0BMJ<\/em>\u00a0articles have withdrawn statements about the adverse effects of statins. The papers inaccurately cite an earlier publication and therefore may overstate\u00a0the incidence of adverse effects. As a result, the two papers have drawn much criticism and set off a kerfuffle involving the editor of\u00a0BMJ<\/em>\u00a0and\u00a0<\/em>a highly prominent British trialist who is demanding a full retraction of the articles. But the controversy probably won’t be resolved any time soon, since an independent panel, which is being assembled to decide the issue,\u00a0has not yet begun its work.<\/p>\n

In\u00a0an editorial published in BMJ<\/em><\/a>, the journal’s editor-in-chief,\u00a0Fiona Godlee, explains the reason for the corrections and the lingering controversy. In October 2013, BMJ<\/em> published two articles that cited the same study by\u00a0Zhang and colleagues<\/a>\u00a0to support the statement that statin side effects occur in 18-20% of patients.\u00a0The first article, by\u00a0Abramson and colleagues<\/a>, reanalyzed data from the Cholesterol Treatment Trialists\u2019 (CTT) Collaboration. The second article, by\u00a0Aseem Malhotra<\/a>, questioned the role of saturated fat in heart disease.\u00a0But, writes Godlee, the articles “did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature” of the data in the paper by\u00a0Zhang and colleagues<\/a>.<\/p>\n

The aim of the editorial, she writes, is “to alert readers, the media, and the public to the withdrawal of these statements so that patients who could benefit from statins are not wrongly deterred from starting or continuing treatment because of exaggerated concerns over side effects.”<\/p>\n

Following the initial publication of the two BMJ<\/em> articles, the head of the CTT Collaboration, Rory Collins, contacted Godlee on several occasions to express his concerns about the papers, though he declined requests to respond in\u00a0BMJ<\/em>. The\u00a0BMJ\u00a0<\/em>editors agreed with the authors of the two studies on the wording of a published correction (see below), but Collins still requested a full retraction. Godlee reports that she is uncertain “whether the error is sufficient for retraction, given that the incorrect statements were in each case secondary to the article\u2019s primary focus.” As a result, BMJ<\/em> is convening an outside panel of experts “with no dog in this fight.”<\/p>\n

Here is the full wording of the two corrections:<\/p>\n

Should people at low risk of cardiovascular disease take a statin?<\/strong><\/p>\n

The conclusion and summary box of this Analysis article by Abramson and colleagues (BMJ<\/i>\u00a02013;347:f6123, doi:10.1136\/bmj.f6123) stated that side effects of statins occur in about 18-20% of patients. The authors withdraw this statement. Although it was based on statements in the referenced observational study by Zhang and colleagues, that \u201cthe rate of reported statin-related events to statins was nearly 18%,\u201d(1) the article did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of the study.<\/p>\n

Zhang et al observed that the rate of statin related events found in their study (18%) was \u201csubstantially higher than the 5% to 10% usually described in randomized, placebo-controlled, clinical trials.\u201d Two caveats must be considered. As Zhang et al point out, the rate of statin related events reported in their study was uncontrolled and therefore may be inflated because events attributed to statins might have occurred in a placebo group as well. In addition, although Zhang et al do not make this point, the 5-10% rate quoted by Zhang et al as having been observed in randomised trials was, in many cases, similar in both active and placebo groups.<\/p>\n

The exact rate of statin related adverse events in people at low risk of cardiovascular disease remains uncertain. Clinical trials may underestimate the frequency of statin related adverse events because of patient selection, exclusion of older patients and those with comorbid conditions or potential drug interactions, under-representation of women, and selection bias created by willingness to participate in a clinical trial. In addition, when compared with the full clinical study reports, published accounts of clinical trials in medical journals report only a minority of adverse events.(2) Access to the full data from the trials of statins would help to determine the comparative rates of serious adverse events in statin and control groups but probably would not help to determine the frequency of less than serious adverse events.<\/p>\n

The authors also mistakenly reported that Zhang et al found that \u201c18% of statin treated patients had discontinued therapy (at least temporarily) because of statin related events.\u201d The correct interpretation of the data, as confirmed to\u00a0The BMJ<\/i>\u00a0by Zhang et al, is as follows. Based on review of structured electronic medical record categories and automated review of unstructured narratives from follow-up visits of 107,835 patients over eight years, 18,778 of all study patients (17.4%) had a statin related event documented during the study. Among those who experienced a statin related event, only 59.2% had statin therapy discontinued at least temporarily. However, because of possible miscategorisation resulting from the limited options in the electronic medical record \u00a0for recording reasons for discontinuation of statin therapy, Zhang et al concluded that \u201cas many as 87%\u201d of these discontinuations could have been due to statin-related events. This equates to up to 9% of the study population having possibly discontinued statin therapy as a consequence of statin related events, rather than the 18% cited.<\/p>\n

The primary finding of Abramson and colleague\u2019s article\u2014that the Cholesterol Treatment Trialists\u2019 data failed to show that statins reduced the overall risk of mortality among people with <20% risk of cardiovascular disease over the next 10 years\u2014was not challenged in the process of communication about this correction.<\/p>\n

1\u00a0\u00a0 \u00a0 Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings.\u00a0Ann Intern Med<\/i>\u00a02013;158:526-34.<\/p>\n

2\u00a0\u00a0 Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervolgyi V, et al. Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data.\u00a0PLoS Med<\/i>\u00a02013;10:e1001526 .<\/p>\n

Cite this as:<\/b>\u00a0BMJ<\/i>\u00a02014;348:g3329<\/p>\n

\u00a0<\/strong><\/p>\n

Saturated fat is not the major issue<\/strong><\/p>\n

This Observations article (BMJ<\/i>\u00a02013;347:f6340, doi:10.1136\/bmj.f6340) by Aseem Malhotra stated that a recent \u201creal world\u201d study of 150<thin>000 patients who were taking statins showed \u201cunacceptable\u201d side effects\u2014including myalgia, gastrointestinal upset, sleep and memory disturbance, and erectile dysfunction\u2014in 20% of participants. The author withdraws this statement. Although it was based on statements in the referenced observational study by Zhang and colleagues that \u201cthe rate of reported statin-related events to statins was nearly 18%,\u201d (1) the article did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of the study.<\/p>\n

1\u00a0\u00a0 \u00a0 Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings.\u00a0Ann Intern Med<\/i>\u00a02013;158:526-34.<\/p>\n

Cite this as:<\/b>\u00a0BMJ<\/i>\u00a02014;348:g3332<\/p>\n

 <\/p><\/blockquote>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

The authors of two\u00a0BMJ\u00a0articles have withdrawn statements about the adverse effects of statins. The papers inaccurately cite an earlier publication and therefore may overstate\u00a0the incidence of adverse effects. As a result, the two papers have drawn much criticism and set off a kerfuffle involving the editor of\u00a0BMJ\u00a0and\u00a0a highly prominent British trialist who is demanding a […]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,7],"tags":[2256,2257,970,515,584],"class_list":["post-43271","post","type-post","status-publish","format-standard","hentry","category-general","category-prevention","tag-bmj","tag-ctt","tag-retractions","tag-side-effects","tag-statins"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/43271","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\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=43271"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/43271\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=43271"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=43271"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=43271"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}