Faculty Bibliography

BACKGROUND: In the Occluded Artery Trial (OAT), 2,201 stable patients with an occluded infarct-related artery (IRA) were randomized to percutaneous coronary intervention (PCI) or optimal medical treatment alone (MED). There was no difference in the primary end point of death, reinfarction, or congestive heart failure (CHF). We examined the prognostic impact of prerandomization stress testing. METHODS: Stress testing was required by protocol except for patients with single-vessel disease and akinesis/dyskinesis of the infarct zone. The presence of severe inducible ischemia was an exclusion criterion for OAT. We compared outcomes based on performance and results of stress testing. RESULTS: Five hundred ninety-eight (27%) patients (297 PCI, 301 MED) underwent stress testing. Radionuclide imaging or stress echocardiography was performed in 40%. Patients who had stress testing were younger (57 vs 59 years); had higher ejection fractions (49% vs 47%); and had lower rates of death (7.8% vs 13.2%), class IV CHF (2.4% vs 5.5%), and the primary end point (13.9% vs 18.9%) than patients without stress testing (all P < .01). Mild-moderate ischemia was observed in 40% of patients with stress testing and was not related to outcomes. Among patients with inducible ischemia, outcomes were similar for PCI and MED (all P > .10). CONCLUSIONS: In OAT, patients who underwent stress testing had better outcomes than patients who did not, likely related to differences in baseline characteristics. In patients managed with optimal medical therapy or PCI, mild-moderate inducible ischemia was not related to outcomes. The lack of benefit for PCI compared to MED alone was consistent regardless of whether stress testing was performed or inducible ischemia was present

BACKGROUND: The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy. METHODS: We compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in high-risk patients in stable condition who had a totally occluded infarct-related artery 3 to 28 days after myocardial infarction. In 951 patients (44% of those eligible), we assessed quality of life by means of a battery of tests that included two principal outcome measures, the Duke Activity Status Index (DASI) (which measures cardiac physical function on a scale from 0 to 58, with higher scores indicating better function) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being). Structured quality-of-life interviews were performed at baseline and at 4, 12, and 24 months. Costs of treatment were assessed for 458 of 469 patients in the United States (98%), and 2-year cost-effectiveness was estimated. RESULTS: At 4 months, the medical-therapy group, as compared with the PCI group, had a clinically marginal decrease of 3.4 points in the DASI score (P=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. For the 469 patients in the United States, cumulative 2-year costs were approximately $7,000 higher in the PCI group (P<0.001), and the quality-adjusted survival was marginally longer in the medical-therapy group. CONCLUSIONS: PCI was associated with a marginal advantage in cardiac physical function at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and was associated with marginally longer quality-adjusted survival. (ClinicalTrials.gov number, NCT00004562.)

BACKGROUND: The Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP) tested the hypothesis that opening a persistently occluded infarct-related artery by percutaneous coronary intervention and stenting (PCI) after the acute phase of myocardial infarction compared with optimal medical therapy alone reduces markers of vulnerability to ventricular arrhythmias. METHODS AND RESULTS: Between April 2003 and December 2005, 300 patients with an occluded native infarct-related artery 3 to 28 days (median, 12 days) after myocardial infarction were randomized to PCI or optimal medical therapy. Ten-minute digital Holter recordings were obtained before randomization, at 30 days, and at 1 year. The primary end point was the change in alpha1, a nonlinear heart rate variability parameter, between baseline and 1 year. Major secondary end points were the changes in the filtered QRS duration on the signal-averaged ECG and variability in T-wave morphology (T-wave variability) between baseline and 1 year. There were no significant differences in the changes in alpha1 (-0.04; 95% CI, -0.12 to 0.04), filtered QRS (2.2 ms; 95% CI, -1.4 to 5.9 ms), or T-wave variability (3.0 microV; 95% CI, -4.8 to 10.7 microV) between the PCI and medical therapy groups (medical therapy change minus PCI change). Multivariable analysis revealed that the results were unchanged after adjustment for baseline clinical variables and medication treatments during the Holter recordings. CONCLUSIONS: PCI with stenting of a persistently occluded infarct-related artery during the subacute phase after myocardial infarction compared with medical therapy alone had no significant effect on changes in heart rate variability, the time-domain signal-averaged ECG, or T-wave variability during the first year after myocardial infarction. These findings are consistent with the lack of clinical benefit, including no reduction in sudden death, with PCI for stable patients with persistently occluded infarct-related arteries after myocardial infarction in the main OAT

AIMS: The Occluded Artery Trial (OAT) (n = 2201) showed no benefit for routine percutaneous intervention (PCI) (n = 1101) over medical therapy (MED) (n = 1100) on the combined endpoint of death, myocardial infarction (MI), and class IV heart failure (congestive heart failure) in stable post-MI patients with late occluded infarct-related arteries (IRAs). We evaluated the potential for selective benefit with PCI over MED for patients enrolled early in OAT. METHODS AND RESULTS: We explored outcomes with PCI over MED in patients randomized to the </=3 calendar days and </=7 calendar days post-MI time windows. Earlier, times to randomization in OAT were associated with higher rates of the combined endpoint (adjusted HR 1.04/day: 99% CI 1.01-1.06; P < 0.001). The 48-month event rates for </=3 days, </=7 days post-MI enrolled patients were similar for PCI vs. MED for the combined and individual endpoints. There was no interaction between time to randomization defined as a continuous (P = 0.55) or categorical variable with a cut-point of 3 days (P = 0.98) or 7 days (P = 0.64) post-MI and treatment effect. CONCLUSION: Consistent with overall OAT findings, patients enrolled in the </=3 day and </=7 day post-MI time windows derived no benefit with PCI over MED with no interaction between time to randomization and treatment effect. Our findings do not support routine PCI of the occluded IRA in trial-eligible patients even in the earliest 24-72 h time window

OBJECTIVE: To evaluate the distribution and determinants of myocardial perfusion grade (MPG) following late recanalization of persistently occluded infarct-related arteries (IRA). BACKGROUND: MPG reflects microvascular integrity. It is an independent prognostic factor following myocardial infarction, but has been studied mainly in the setting of early reperfusion. The occluded artery trial (OAT) enrolled stable patients with persistently occluded IRAs beyond 24 hr and up to 28 days post-MI. METHODS: Myocardial blush was assessed using TIMI MPG grading in 261 patients with TIMI 3 epicardial flow following IRA PCI. Patients demonstrating impaired (0-1) versus preserved (2-3) MPG were compared with regard to baseline clinical and pre-PCI angiographic characteristics. RESULTS: Impaired MPG was observed in 60 of 261 patients (23%). By univariate analysis, impaired MPG was associated with failed fibrinolytic therapy, higher heart rate, lower systolic blood pressure, lower ejection fraction, LAD occlusion, absence of collaterals (P < 0.01) and ST elevation MI, lower diastolic blood pressure, and higher systolic sphericity index (P < 0.05). By multivariable analysis, higher heart rate, LAD occlusion, absence of collaterals and higher systolic sphericity index (P < 0.01), and lower systolic blood pressure (P < 0.05) were independently associated with impaired MPG. CONCLUSION: Preserved microvascular integrity was present in a high proportion of patients following late recanalization of occluded IRAs post-MI. Presence of collaterals was independently associated with preserved MPG and likely accounted for the high frequency of preserved myocardial perfusion in this clinical setting. Impaired MPG was associated with baseline clinical and angiographic features consistent with larger infarct size

OBJECTIVES: To determine predictors of outcome and examine the influence of baseline risk on therapeutic impact of late mechanical opening of a persistently occluded infarct related artery (IRA) after myocardial infarction (MI) in stable patients. BACKGROUND: Previous studies in patients with acute coronary syndromes suggest that the impact of IRA recanalization on clinical outcome is greatest in patients at highest risk. METHODS: Of 2201 patients (age 58.6+/-11.0) with IRA occlusion on days 3 to 28 after MI in the Occluded Artery Trial (OAT), 1101 were assigned to PCI and 1100 to medical therapy alone, and followed for a mean of 3.2 years. The primary end point was a composite of death, reinfarction, or NYHA class IV heart failure. Interaction of treatment effect with tertiles of predicted survival were examined using the Cox survival model. RESULTS: The 5-year rate for the primary endpoint was 18.9% versus 16.1% for patients assigned PCI and medical treatment alone (MED) respectively (HR=1.14;95% CI:0.92-1.43, p=0.23). Lack of benefit of PCI was consistent across the risk spectrum for both the primary endpoint and total mortality, including for the highest tertile (33.9% PCI versus 27.3 % MED, HR=1.27;99% CI:0.87-1.85 primary endpoint and 23.5% PCI versus 21.7% MED, HR=1.16,99% CI: 0.73-1.85 mortality). The independent predictors of the composite outcome were: history of heart failure (HR=2.06,p<0.001), peripheral vascular disease (HR=1.93,p=0.001), diabetes (HR=1.49,p=0.002), rales (HR=1.88,p<0.001), decreasing: ejection fraction (HR=1.48 per 10%,p<0.001), days from MI to randomization (HR=1.04 per day,p<0.001), and glomerular filtration rate (HR=1.11 per 10mL/min/1.73m(2),p<0.001). CONCLUSIONS: In OAT, there was no variation in the effect of PCI on clinical outcomes at different levels of patient risk, including the subset with very high event rates