{"id":31540,"date":"2012-09-04T10:24:57","date_gmt":"2012-09-04T14:24:57","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=31540"},"modified":"2012-09-04T10:33:11","modified_gmt":"2012-09-04T14:33:11","slug":"esc-trials-the-best-and-the-worst","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/09\/04\/esc-trials-the-best-and-the-worst\/","title":{"rendered":"ESC Trials: The Best And The Worst"},"content":{"rendered":"

Two trials presented at the ESC this year\u00a0\u2014 WOEST<\/a>\u00a0and\u00a0IABP-SHOCK II\u00a0<\/a>\u2014 are great examples of the way medicine is supposed to work. Another trial,\u00a0FAME 2<\/a>, is an example of so many of the things that can go wrong.<\/p>\n

WOEST and IABP-SHOCK II<\/strong><\/p>\n

WOEST and IABP-SHOCK II are remarkably similar.\u00a0Both trials tested conventional wisdom and found it lacking.\u00a0WOEST examined the routine use of aspirin in “triple therapy”, which is when people already taking an anticoagulant undergo PCI and then receive an additional antiplatelet drug and aspirin. IABP-SHOCK II tested the routine use of\u00a0circulatory support with intra-aortic balloon counterpulsation (IABP) for patients in cardiogenic shock following MI for whom early revascularization is planned.<\/p>\n

Despite scant evidence, both of the ideas tested in these trials had received class 1 recommendations in the guidelines and were widely used in clinical practice.\u00a0And both trials provided near definitive proof that the conventional wisdom was completely and utterly wrong.<\/p>\n

This is the way science is supposed to work: an idea gets put to a fair test. Judging from the initial response to these trials, it seems likely that the cardiology community will rapidly accept the findings, and guidelines and clinical practice likely will change in short order to reflect the new evidence base.<\/p>\n

FAME 2<\/strong><\/p>\n

FAME 2 also addressed, or claimed to address, an important question. Although the evidence base for PCI in stable angina had always been weak or nonexistent, its popularity had undergone exponential growth for many years, until COURAGE famously put the brakes on this growth. When fractional flow reserve (FFR) first came along, it was viewed with considerable suspicion in the interventional community, since in many respects it helped confirm the findings of COURAGE by appearing to demonstrate that a significant percentage of lesions intervened upon were not ischemic and therefore almost certainly didn’t benefit the patients who had undergone PCI.<\/p>\n

Eventually, however, the interventional cardiology community found a path to renewal with FFR. Perhaps, it reasoned, instead of being used to illustrate the lack of utility of PCI, FFR could be used to\u00a0guide<\/em>\u00a0PCI decisions, limiting interventions to ischemic lesions that would benefit from PCI.<\/p>\n

This is where FAME 2 comes into the picture. In the trial, patients who had at least one functionally significant lesion, as defined by FFR, were randomized to FFR-guided PCI plus medical therapy or medical therapy alone.\u00a0The trial was stopped early, after only about half of the intended number of patients were enrolled, because of a significant reduction in the primary endpoint (the composite of death, MI, or urgent revascularization) in the PCI group compared to the medical- therapy-alone group.<\/p>\n

The FAME 2 investigators, along with many members of the interventional cardiology community, have presented the results of the trial as a definitive response to the questions about PCI raised by COURAGE. In\u00a0an ESC press release<\/a>, FAME 2 coordinator\u00a0Bernard De Bruyne said:<\/p>\n

“With this new knowledge, I believe that FFR should become the standard of care for treating most patients with stable coronary artery disease and significant coronary narrowings.”<\/p><\/blockquote>\n

The Society for Cardiovascular Angiography and Interventions (SCAI) was so excited about the results of FAME 2 that it rushed out\u00a0an e-publication of a “President’s Page” perspective on FAME 2,<\/a>\u00a0written by SCAI president J. Jeffrey Marshall and interventional cardiologist Ajay Kirtane, arguing that “FAME 2 offers\u00a0the best data currently available to guide” treatment. The perspective of most interventional cardiologists is probably best summarized by this\u00a0headline published on TCTMD<\/a>: “PCI Bests Medical Therapy in Stable Patients with Proven Ischemia.”<\/p>\n

The sad thing about these simplistic responses to FAME 2\u00a0\u2014 and the reason why I use this trial as an example of a poor model for clinical trials\u00a0\u2014 is that there is no acknowledgement of the extraordinary division of opinion about this trial and its meaning. The SCAI document discusses the FAME 2 publication but does not even reference, or respond to, the issues raised in\u00a0an editorial accompanying the publication of FAME 2 in the\u00a0New England Journal of Medicine<\/em><\/a>. That editorial, by\u00a0Bill Boden, the principal investigator\u00a0of the COURAGE trial, delivered a trenchant attack on the view that FAME 2 represents anything like a definitive response to COURAGE.<\/p>\n

I summarized Boden’s points in\u00a0my previous news story about FAME 2<\/a>:<\/p>\n