{"id":42552,"date":"2014-03-30T14:28:56","date_gmt":"2014-03-30T18:28:56","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=fellowship-training&p=42552"},"modified":"2014-03-30T15:03:57","modified_gmt":"2014-03-30T19:03:57","slug":"stage-set-for-phase-iv-trials-of-pcsk9-inhibition","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/03\/30\/stage-set-for-phase-iv-trials-of-pcsk9-inhibition\/","title":{"rendered":"Stage Set for Phase IV Trials of PCSK9 Inhibition"},"content":{"rendered":"

Several Cardiology fellows who are attending ACC.14 in Washington, D.C. this week are blogging for CardioExchange. The fellows include\u00a0Kumar Dharmarajan<\/a><\/strong>,\u00a0Seth Martin<\/strong><\/a>, and\u00a0Saurav Chatterjee<\/strong><\/a>. For more of our ACC.14 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our\u00a0ACC.14 Headquarters<\/a>.<\/em><\/p>\n

Surrounded by tall glowing curtains colored in purple, blue, orange, red,\u00a0and hot pink, I’m sitting here in the main tent at the Sunday morning LBCT\u00a0session feeling the enthusiasm build for PCSK9 inhibitors. I’m typing as\u00a0the presentation of GAUSS-2 by Dr. Stroes completes a series of five phase III\u00a0evolocumab (AMG 145) presentations here at ACC.14.<\/p>\n

\"\"<\/p>\n

Yesterday, MENDEL-2 confirmed efficacy as monotherapy, DESCARTES showed\u00a0durability out to 52 weeks, and RUTHERFORD-2 addressed the heterozygous FH\u00a0population. Now I’ve just I watched Dr. Robinson present LAPLACE-2, showing\u00a0that evolocumab significantly lowered LDL-C over the course of a few months\u00a0in patients with hypercholesterolemia on background statin therapy. And now\u00a0GAUSS-2 is showing efficacy and safety in a well-defined statin-intolerant\u00a0population. Overall, the results are complementary, consistent, and\u00a0favorable.<\/p>\n

We are seeing that LDL-C consistently gets cut in half or more, but what’s\u00a0also very cool here is that Lp(a) is going down by about 25-30%. To date,\u00a0we haven’t had a good armamentarium against Lp(a), with niacin being the\u00a0main option. Another potential tool for this predominantly genetic disorder, which\u00a0predisposes families to premature cardiovascular disease, is warmly\u00a0welcomed.<\/p>\n

The stage is set for the phase IV trials of ASCVD outcomes. As Dr. Robinson\u00a0mentioned, FOURIER is underway, using evolocumab on top of statin therapy\u00a0in 22,500 patients with clinical ASCVD.<\/p>\n

Will I be shocked if the phase IV trials don’t work? You better believe it.\u00a0The biology makes sense. The epidemiology was consistent. The phase III\u00a0trials look great. Are you also feeling the enthusiasm build? Do you agree\u00a0that PCSK9 inhibitors are a likely game changer? Assuming the phase IV trials\u00a0pan out, can you think of patients in your practice who will find this to be a\u00a0useful option?<\/p>\n

Regarding safety, we’re not seeing a signal for adverse effects in the\u00a0realm of neurocognitive effects in the overall evolocumab program. However,\u00a0the FDA has asked for neurocognitive sub-studies in the phase IV trials.\u00a0Anyone out there have more insight into this? Is this really a good use of\u00a0resources? Another approach: support n-of-1 trials in patients in whom a\u00a0cognitive concern arises.<\/p>\n","protected":false},"excerpt":{"rendered":"

Seth Martin, a fellow blogging at ACC.14, discusses some exciting developments taking place at the conference.<\/p>\n","protected":false},"author":370,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[2171,210,584],"class_list":["post-42552","post","type-post","status-publish","format-standard","hentry","category-prevention","tag-acc-14","tag-cholesterol","tag-statins"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42552","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\/370"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=42552"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42552\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=42552"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=42552"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=42552"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}