{"id":29123,"date":"2012-05-18T13:25:51","date_gmt":"2012-05-18T17:25:51","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=interventional&p=29123"},"modified":"2012-05-18T13:25:51","modified_gmt":"2012-05-18T17:25:51","slug":"fame-ii-another-study-abides-in-infamy","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/05\/18\/fame-ii-another-study-abides-in-infamy\/","title":{"rendered":"FAME II: Another Study Abides in Infamy"},"content":{"rendered":"

In FAME II<\/a>, a prospective study conducted at 28 centers in Europe and the United States,\u00a0>1200 patients with ischemia (as determined by fractional flow reserve [FFR]) were randomly assigned to receive (a) PCI (with a DES) and optimal medical therapy (OMT) or (b) OMT alone. The primary endpoint was a composite of death, myocardial infarction (MI), and unplanned hospitalization leading to urgent revascularization within 24 months of randomization.<\/p>\n

Patients were considered to have urgent revascularization if they (a) entered the hospital through the emergency department and their revascularization procedures were performed during the same hospitalization, or (b) presented to clinic with increased angina symptoms.<\/p>\n

The study was halted prematurely by the data safety monitoring board (DSMB)\u00a0because of\u00a0a difference in the incidence of urgent revascularization in the two study arms; the rates of death or MI were similar.\u00a0In other words, urgent revascularization was performed for symptom relief, not MI. According to\u00a0results presented at EuroPCR<\/a>, the rate of unplanned revascularization within 6 months in the OMT and PCI+OMT groups was 12% \u00a0and 2%, respectively.<\/p>\n

These data can be interpreted in\u00a0one of\u00a0two ways. One can conclude that\u00a0because urgent revascularization was required about 11 times more often in the OMT group than in the PCI+OMT group, PCI in patients with abnormal FFR results in an improved outcome. Alternatively, one can conclude that almost <\/em>90% of patients in the OMT+PCI group had an unnecessary (and costly) PCI<\/em>.<\/p>\n

The fact that the DSMB prematurely stopped this trial is troubling<\/em><\/strong> for several reasons.<\/p>\n

1)\u00a0 Fewer than 40% of the patients had been followed for 2 months or longer before the study was stopped.<\/p>\n

2)\u00a0 The trial was discontinued on the basis of a \u201csoft endpoint\u201d (i.e., symptom-prompted revascularization).\u00a0\u00a0Participants who did not undergo PCI experienced no \u201creal” harm (i.e., death or MI).<\/p>\n

3)\u00a0 Randomizing patients with ischemia to OMT alone is problematic.\u00a0Because of the perception\u00a0\u2014 held by both physicians and patients\u00a0\u2014 that ischemic myocardium should be revascularized, PCI is almost always performed in such patients.\u00a0In these individuals, any symptom becomes angina or an anginal equivalent and, as a result, PCI is indicated.<\/p>\n

It is well known that trials that are stopped early because of an apparent treatment difference are prone to exaggerate the true effect of the intervention. They often stop on a \u201crandom high,\u201d whereas the observed difference might well have regressed to the true effect if they had been continued for a longer time period.<\/p>\n

Would you have considered it unethical to continue this trial, or would you have allowed it to continue?<\/em><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

In FAME II, a prospective study conducted at 28 centers in Europe and the United States,\u00a0>1200 patients with ischemia (as determined by fractional flow reserve [FFR]) were randomly assigned to receive (a) PCI (with a DES) and optimal medical therapy (OMT) or (b) OMT alone. The primary endpoint was a composite of death, myocardial infarction […]<\/p>\n","protected":false},"author":214,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[9],"tags":[1281,1027,838,301],"class_list":["post-29123","post","type-post","status-publish","format-standard","hentry","category-interventional-cardiology","tag-fame-ii","tag-ffr","tag-optimal-medical-therapy","tag-pci"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/29123","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\/214"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=29123"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/29123\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=29123"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=29123"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=29123"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}