Occluded Artery Trial (OAT) Presented at The American Heart Association Scientific Session 2006 Presented by Dr. Judith S. Hochman OAT Trial

www. Clinical trial results.org OAT Trial: Background The goal of the trial was to evaluate percutaneous coronary intervention (PCI) compared with medical therapy among stable, high-risk patients with persistent total occlusion of the infarct-related artery post- myocardial infarction (MI).The goal of the trial was to evaluate percutaneous coronary intervention (PCI) compared with medical therapy among stable, high-risk patients with persistent total occlusion of the infarct-related artery post- myocardial infarction (MI). Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Hypothesis A strategy of routine PCI for total occlusion of the infarct- related artery 3-28 days after acute MI would reduce the occurrence of the composite of death, reinfarction, or New York Heart Association (NYHA) class IV heart failure.A strategy of routine PCI for total occlusion of the infarct- related artery 3-28 days after acute MI would reduce the occurrence of the composite of death, reinfarction, or New York Heart Association (NYHA) class IV heart failure. Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Study Design  Primary Endpoints: Death, MI, or NYHA class IV heart failure PCI with stenting n=1082 n=1082 Medical Therapy n=1084 n= patients with angiography on day 3-28 post-MI with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both Exclusions: NYHA class III or IV heart failure, shock, serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing. Randomized. 22% female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated 2166 patients with angiography on day 3-28 post-MI with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both Exclusions: NYHA class III or IV heart failure, shock, serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing. Randomized. 22% female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Primary Endpoint The primary endpoint of death, reinfarction, or NYHA class IV heart failure occurred in 17.2% of the PCI group and 15.6% of the medical therapy group ([HR] 1.16, p=0.20).The primary endpoint of death, reinfarction, or NYHA class IV heart failure occurred in 17.2% of the PCI group and 15.6% of the medical therapy group ([HR] 1.16, p=0.20). Primary Endpoint of death, reinfarction, NYHA class IV heart failure (% patients) Hazard Ratio 1.16, p=0.20 Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Primary Component Endpoints Total reinfarction trended higher in the PCI group (7.0% vs. 5.3%, HR 1.36, p=0.13), as did nonfatal reinfarction (6.9% vs. 5.0%, HR 1.44, p=0.08).Total reinfarction trended higher in the PCI group (7.0% vs. 5.3%, HR 1.36, p=0.13), as did nonfatal reinfarction (6.9% vs. 5.0%, HR 1.44, p=0.08). Repeated elevation of cardiac biomarkers within 48 hours of randomization occurred significantly more frequently in the PCI group (10.0% vs. 3.3%, p<0.001).Repeated elevation of cardiac biomarkers within 48 hours of randomization occurred significantly more frequently in the PCI group (10.0% vs. 3.3%, p<0.001). There was no difference in the individual endpoints of death (9.1% for PCI vs. 9.4% for medical therapy, p=0.83) or NYHA class IV heart failure (4.4% vs. 4.5%, p=0.92) between the treatment groups.There was no difference in the individual endpoints of death (9.1% for PCI vs. 9.4% for medical therapy, p=0.83) or NYHA class IV heart failure (4.4% vs. 4.5%, p=0.92) between the treatment groups. Primary Component Endpoints (% patients) TotalReinfarction Presented at AHA 2006 % patients NonfatalReinfarctionDeath Repeated ↑ of Cardiac Biomarkers NYHA Class IV Heart Failure p=0.13p=0.13 p=0.08p=0.08 p<0.001p<0.001 p=0.83p=0.83 p=0.92p=0.92

www. Clinical trial results.org OAT Trial: Summary Among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-MI, performance of PCI 3-28 days post-MI was not associated with a difference in the composite of death, reinfarction, or NYHA class IV heart failure through a mean follow-up of 3 years compared with medical therapy.Among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-MI, performance of PCI 3-28 days post-MI was not associated with a difference in the composite of death, reinfarction, or NYHA class IV heart failure through a mean follow-up of 3 years compared with medical therapy. Despite no reduction in the composite endpoint, PCI was associated with a trend toward higher rates of reinfarction compared with medication therapy.Despite no reduction in the composite endpoint, PCI was associated with a trend toward higher rates of reinfarction compared with medication therapy. Among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-MI, performance of PCI 3-28 days post-MI was not associated with a difference in the composite of death, reinfarction, or NYHA class IV heart failure through a mean follow-up of 3 years compared with medical therapy.Among stable, high-risk patients with persistent total occlusion of the infarct-related artery post-MI, performance of PCI 3-28 days post-MI was not associated with a difference in the composite of death, reinfarction, or NYHA class IV heart failure through a mean follow-up of 3 years compared with medical therapy. Despite no reduction in the composite endpoint, PCI was associated with a trend toward higher rates of reinfarction compared with medication therapy.Despite no reduction in the composite endpoint, PCI was associated with a trend toward higher rates of reinfarction compared with medication therapy. Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Summary (cont.) The reinfarctions were not only procedural-related infarcts (i.e., early procedural enzymatic leaks), but true ST elevation reinfarctions that accumulated throughout follow-up.The reinfarctions were not only procedural-related infarcts (i.e., early procedural enzymatic leaks), but true ST elevation reinfarctions that accumulated throughout follow-up. One explanation for the trend toward an increase in reinfarctions with PCI may be embolization resulting in myocardial damage and impaired collateral flow.One explanation for the trend toward an increase in reinfarctions with PCI may be embolization resulting in myocardial damage and impaired collateral flow. Presence of persistent total occlusion remains a problem for a sizeable cohort of patients for whom suitable treatment is lacking.Presence of persistent total occlusion remains a problem for a sizeable cohort of patients for whom suitable treatment is lacking. The reinfarctions were not only procedural-related infarcts (i.e., early procedural enzymatic leaks), but true ST elevation reinfarctions that accumulated throughout follow-up.The reinfarctions were not only procedural-related infarcts (i.e., early procedural enzymatic leaks), but true ST elevation reinfarctions that accumulated throughout follow-up. One explanation for the trend toward an increase in reinfarctions with PCI may be embolization resulting in myocardial damage and impaired collateral flow.One explanation for the trend toward an increase in reinfarctions with PCI may be embolization resulting in myocardial damage and impaired collateral flow. Presence of persistent total occlusion remains a problem for a sizeable cohort of patients for whom suitable treatment is lacking.Presence of persistent total occlusion remains a problem for a sizeable cohort of patients for whom suitable treatment is lacking. Presented at AHA 2006

www. Clinical trial results.org OAT Trial: Summary (cont.) Early reperfusion therapy, the goal of ST elevation MI treatment, with either primary PCI or thrombolysis, is not indicated for patients who present late, often with persistent total occlusion.Early reperfusion therapy, the goal of ST elevation MI treatment, with either primary PCI or thrombolysis, is not indicated for patients who present late, often with persistent total occlusion. The present study, the largest randomized trial to date in this population, does not support the use of late PCI for stable but persistent total occlusion.The present study, the largest randomized trial to date in this population, does not support the use of late PCI for stable but persistent total occlusion. Early reperfusion therapy, the goal of ST elevation MI treatment, with either primary PCI or thrombolysis, is not indicated for patients who present late, often with persistent total occlusion.Early reperfusion therapy, the goal of ST elevation MI treatment, with either primary PCI or thrombolysis, is not indicated for patients who present late, often with persistent total occlusion. The present study, the largest randomized trial to date in this population, does not support the use of late PCI for stable but persistent total occlusion.The present study, the largest randomized trial to date in this population, does not support the use of late PCI for stable but persistent total occlusion. Presented at AHA 2006