| \n Endpoints<\/strong><\/p>\n<\/td>\n PCI + Medical Therapy<\/strong><\/p>\n<\/td>\n Medical Therapy Alone<\/strong><\/p>\n<\/td>\n P<\/em> value<\/strong><\/p>\n<\/td>\n<\/tr>\n 4.3%<\/p>\n<\/td>\n 12.7%<\/p>\n<\/td>\n <0.001<\/p>\n<\/td>\n<\/tr>\n 0.2%<\/p>\n<\/td>\n 0.7%<\/p>\n<\/td>\n 0.31<\/p>\n<\/td>\n<\/tr>\n 3.4%<\/p>\n<\/td>\n 3.2%<\/p>\n<\/td>\n 0.89<\/p>\n<\/td>\n<\/tr>\n 1.6%<\/p>\n<\/td>\n 11.1%<\/p>\n<\/td>\n <0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \u00a0<\/em><\/strong><\/p>\n Does this settle the issue that ischemia should guide revascularization?<\/strong>\u00a0Consider these points:<\/p>\n 1. The Data and Safety Monitoring Board halted the study on the basis of differences in the weakest component (urgent revascularization) of a composite endpoint in a setting where referral bias may have influenced the outcome. Interestingly, no formal rules for stopping the study prematurely were specified.\u00a0How, then, was study termination decided?<\/em> On average, trials that are stopped prematurely for benefit overestimate that benefit by 30%.<\/p>\n 2. Half the patients undergoing urgent revascularization had no objective evidence of ischemia (i.e., elevated biomarkers or ECG changes). Is this really \u201curgent revascularization\u201d or simply a bias to revascularize subjects with abnormal FFR (vs. those with normal FFR)?<\/em><\/p>\n 3. The post-PCI diagnosis of MI was established using CK-MB levels (above 5 or 10 times the upper reference limit), whereas the diagnosis of MI in the setting of ACS was established with either CK-MB or troponin levels. Doesn\u2019t this minimize the rate of peri-PCI MI?<\/em><\/p>\n 4. The sponsor was \u201cinvolved in the collection and source verification of the data.\u201d What does this mean?<\/p>\n 5. Although the study was designed to follow patients for 2 years, the mean follow-up was only 7 months. Come on now — not only was the study terminated prematurely (when only slightly more than half the planned subjects were enrolled), but the follow-up was truncated as well? \u00a0\u00a0<\/em><\/p>\n 6. Demonstration of a pressure gradient across an epicardial coronary stenosis (i.e., abnormal FFR) is not synonymous with ischemia. Instead, ischemia is a consequence of diminished myocardial tissue perfusion and can be identified by ECG changes, regional myocardial perfusion abnormalities during scintigraphy, wall-motion abnormalities on echocardiography, or abnormal tissue perfusion or metabolism on PET imaging. Given that none of these tests was performed in conjunction with the FFR measurements, we cannot know<\/em> whether an FFR of 0.68 (the mean value in the study) was associated with ischemia.\u00a0In addition, it\u2019s difficult to compare the FAME 2 patients with the COURAGE patients<\/a> (85% of whom had documented ischemia).<\/p>\n 7. On the basis of the FAME II data, one would perform PCI in 100 patients to prevent 9 \u201curgent revascularizations,\u201d only 4 of which are for ischemia (i.e., positive biomarkers or ECG changes) — without reducing the incidence of MI or death. This seems to be a long (and expensive) run for a short slide.<\/p>\n Henry David Thoreau asked for truth rather than FAME (or love or money for that matter).\u00a0What truth do you take from this study? Should we be performing PCI in all stable CAD patients who have abnormal FFR?<\/strong><\/p>\n |