{"id":32780,"date":"2012-11-05T14:30:24","date_gmt":"2012-11-05T19:30:24","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=news&#038;p=32780"},"modified":"2012-11-05T14:48:57","modified_gmt":"2012-11-05T19:48:57","slug":"dalcetrapib-another-hdl-raising-cetp-inhibitor-bites-the-dust","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/11\/05\/dalcetrapib-another-hdl-raising-cetp-inhibitor-bites-the-dust\/","title":{"rendered":"Dalcetrapib: Another HDL-Raising CETP Inhibitor Bites the Dust"},"content":{"rendered":"<p>Another HDL-raising CETP inhibitor has failed to demonstrate cardiovascular benefit in a large clinical trial. With the presentation of the dal-OUTCOMES trial at the American Heart Association in Los Angeles and <a title=\"dal_OUTCOMES\" href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1206797\" target=\"_blank\">simultaneous publication in the\u00a0<em>New England Journal of Medicine<\/em><\/a>, dalcetrapib joins torceptrapib on the list of once-promising CETP inhibitors.<\/p>\n<p>In dal-OUTCOMES, 15,871 patients with a recent acute coronary syndrome were randomized to dalcetrapib\u00a0or placebo. At\u00a0a prespecified interim analysis\u00a0after a median follow-up of 31 months, the Data and Safety Monitoring Board recommended termination of the trial for futility. The\u00a0primary endpoint &#8212; a composite of death from CHD, nonfatal MI, ischemic stroke, unstable angina, or cardiac arrest with resuscitation &#8212; occurred in 8.3% of dalcetrapib recipients and 8.0% of placebo recipients (HR, 1.04; 95% CI, 0.93-1.16; <em>P<\/em>=0.52).<\/p>\n<p>As expected, dalcetrapib raised HDL (by about 30%) and had little effect on LDL. However, there was no correlation between baseline HDL level and clinical outcome. Furthermore, dalcetrapib treatment resulted in mean increases of 18% in\u00a0CRP level and of 0.6 mm Hg in systolic blood pressure.<\/p>\n<p>The chair of the trial, Gregory Schwartz, said that the\u00a0small increases in blood pressure and CRP might explain the results. The discussant for the trial, Alan Tall, said that the decision to stop the trial prematurely was rational. In addition to the changes in blood pressure and CRP, he offered several additional possible reasons for the drug&#8217;s failure to improve outcomes:<\/p>\n<div>\n<ul>\n<li>Moderate HDL elevation in patients who are already well treated may have little impact. It is possible that much larger elevations in HDL will be required to alter the course of disease.<\/li>\n<li>CETP inhibitors may produce a form of HDL that does not enhance reverse cholesterol transport.<\/li>\n<li>Dalcetrapib is only a partial CETP inhibitor. Phase 3 trials of more-potent CETP inhibitors, such as anacetrapib and evacetrapib, may still demonstrate benefit.<\/li>\n<\/ul>\n<p>For related CardioExchange content, go to our <a title=\"AHA2012Headquarterspage\" href=\"http:\/\/blogs.nejm.org\/cardioexchange\/news\/aha-2012-headquarters\/ \" target=\"_blank\">AHA 2012 Headquarters\u00a0page<\/a>.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Another HDL-raising CETP inhibitor has failed to demonstrate cardiovascular benefit in a large clinical trial. With the presentation of the dal-OUTCOMES trial at the American Heart Association in Los Angeles and simultaneous publication in the\u00a0New England Journal of Medicine, dalcetrapib joins torceptrapib on the list of once-promising CETP inhibitors. In dal-OUTCOMES, 15,871 patients with a [&hellip;]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[571,210,209],"class_list":["post-32780","post","type-post","status-publish","format-standard","hentry","category-prevention","tag-cetp-inhibitors","tag-cholesterol","tag-hdl"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/32780","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=32780"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/32780\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=32780"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=32780"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=32780"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}