Article Identification

• Title: Coronary Intervention for Persistent Occlusion after Myocardial Infarction
• Authors: Hochman JS, Lamas GA, Buller CE, et al.
• Citation: N Engl J Med. 2006;355(23):2395-2407.
• DOI: 10.1056/NEJMoa066139

Quick Reference Summary

• In this large multicenter randomized trial (Occluded Artery Trial [OAT]), late percutaneous coronary intervention (PCI) (3-28 days after MI) for persistently occluded infarct-related coronary arteries did not significantly reduce the composite outcome of death, reinfarction, or severe (NYHA class IV) heart failure compared with optimal medical therapy (17.2% vs 15.6%; HR 1.16, 95% CI 0.92-1.45, p=0.20).
• There was also a trend toward higher rates of reinfarction in the PCI group (HR 1.36, 95% CI 0.92-2.00, p=0.13), indicating no clear clinical benefit of routine late PCI in these stable, high-risk patients.

Core Clinical Question

In stable patients with persistent total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction, does routine PCI in addition to optimal medical therapy reduce rates of death, reinfarction, or severe heart failure compared to optimal medical therapy alone?

Background

• Disease or Condition Overview:
  • Myocardial infarction (MI) with ST-segment elevation often requires early reperfusion through primary PCI or thrombolysis; however, some patients present late and do not receive immediate reperfusion.
  • Persistent occlusion of the infarct artery beyond the accepted window for myocardial salvage can lead to adverse remodeling, heart failure, and recurrent ischemic events.
• Prior Data on the Topic:
  • Observational studies suggested that late patency of the infarct artery may improve long-term mortality and reduce adverse remodeling.
  • However, smaller randomized trials yielded conflicting results, and it remained unclear whether routine late PCI in stable post-MI patients conferred any concrete mortality or morbidity benefit.
• Current Standard of Care:
  • Early reperfusion is still the standard for ST-elevation MI whenever possible.
  • In stable, late-presenting patients, optimal medical therapy (including antiplatelets, β-blockers, ACE inhibitors, and statins) is foundational, and late revascularization has been considered on a case-by-case basis.
• Knowledge Gaps Addressed by This Study:
  • Does opening the infarct-related artery days after the MI window has passed provide any additional clinical benefit?
  • Potential concerns included the possibility of procedure-related complications and whether rescuing infarct-zone viability would improve outcomes.
• Study Rationale: The OAT was designed to definitively test whether recanalizing the infarct-related artery 3 to 28 days after MI reduces a composite of death, reinfarction, and NYHA class IV heart failure.

Methods Summary

• Study Design: A multicenter, randomized, controlled trial (Occluded Artery Trial [OAT]).
• Setting and Time Period: Enrolled from February 2000 through December 2005 at multiple international centers.
• Population Characteristics: 2,166 stable, high-risk patients with totally occluded infarct-related arteries (TIMI flow grade 0 or 1) 3 to 28 days post-MI.
• High-risk defined by:
  • an ejection fraction <50% and/or proximal occlusion of a major coronary artery.
• Inclusion Criteria:
  • Age ≥18, stable condition, total occlusion of the culprit artery 3-28 days post-MI, EF <50% or proximal occlusion.
• Exclusion Criteria:
  • Class III–IV heart failure or shock
  • Severe ischemia needing urgent revascularization
  • Significant left main or triple-vessel disease
  • Serum creatinine >2.5 mg/dL.
• Intervention Details:
  • PCI with stent placement plus optimal medical therapy. Glycoprotein IIb/IIIa inhibitors were recommended.
  • “Routine PCI” group aimed to achieve <50% residual stenosis with TIMI 2-3 flow. Stents were mostly bare-metal, with few drug-eluting stents used in later enrollment.
• Control/Comparison Group: Optimal medical therapy alone. Crossovers to PCI were allowed if clinically indicated at the treating physician’s discretion.
• Primary and Secondary Outcomes:
  • Primary: Composite of death, reinfarction, or NYHA class IV heart failure.
  • Secondary: Individual components of the primary outcome, angina, repeated revascularization, and composite at site-determined endpoints.
• Statistical Analysis Approach: Intention-to-treat analysis. Kaplan–Meier estimates for time-to-event outcomes, log-rank test for group comparisons. Cox proportional hazards models adjusted for baseline covariates. Significance threshold for primary endpoint: p<0.0456 (due to interim monitoring).
• Sample Size Calculations: Planned for 2,400 patients, achieving >90% power to detect a 25% relative risk reduction in the composite endpoint.
• Ethics and Funding: Sponsored by the National Heart, Lung, and Blood Institute (NHLBI), with minor in-kind industry contributions. Institutional Review Board approval at each center.

Detailed Results

• Participant Flow and Demographics:
  • 2,166 patients randomized (PCI, n=1,082; Medical therapy, n=1,084). Baseline characteristics well balanced except for slightly higher prevalence of diabetes in the medical therapy group.
• Primary Outcome Results:
  • Death, reinfarction, or severe heart failure occurred in 17.2% of PCI patients vs 15.6% of medical therapy patients over 4 years (HR 1.16, 95% CI 0.92-1.45, p=0.20).
  • No difference in mortality: 9.1% (PCI) vs 9.4% (medical).
  • No difference in severe heart failure: 4.4% (PCI) vs 4.5% (medical).
• Reinfarction Rates:
  • Fatal or nonfatal reinfarction: 7.0% (PCI) vs 5.3% (medical) (HR 1.36, 95% CI 0.92-2.00, p=0.13).
  • Nonfatal reinfarction slightly trended higher in PCI group (6.9% vs 5.0%, HR 1.44, 95% CI 0.96-2.16, p=0.08).
• Secondary Outcomes:
  • Angina reduction favored PCI up to 1 year, but the difference disappeared by year 3.
  • Slight trend toward fewer subsequent revascularizations in the PCI arm compared to crossovers in the medical arm, though not statistically robust for major endpoints.
• Subgroup Analyses:
  • No significant interaction between treatment effect and subgroups (age, sex, infarct location, EF, diabetes, time from MI).
• Adverse Events/Safety Data:
  • PCI-related major complications were rare (0.2% mortality, 0.6% adjudicated reinfarction during the procedure).

Results Table

Authors' Conclusions

• Primary Conclusions:
  • In stable, high-risk patients 3-28 days after MI with total occlusion, routine PCI added to optimal medical therapy did not reduce death, reinfarction, or severe heart failure over a ~4-year period.
• Authors’ Interpretation of Results:
  • The hypothesis that late opening of the infarct artery would improve remodeling and long-term outcomes was not supported.
• Clinical Implications Stated by Authors:
  • Routine late PCI in this population is not warranted as standard practice.
• Future Research Recommendations:
  • Further studies to clarify mechanisms of potential microvascular damage, distal embolization, or reocclusion, and to identify subgroups (if any) potentially benefiting from invasive strategies.

Critical Analysis

A. STRENGTHS

• Large, multicenter, randomized design: 2,166 patients with robust power.
• Strict endpoint adjudication: Performed by a blinded committee.
• High procedural success rate: Reflecting contemporary interventional practice.
• Detailed subgroup analyses: No significant interactions observed.

B. LIMITATIONS

• Open-label design: Could introduce performance bias.
• Slight imbalance in diabetes prevalence: Between groups.
• Stent Usage: Majority used bare-metal stents; drug-eluting stents were minimal.
• Generalizability: Results may not extrapolate to newer-generation stents or advanced imaging–guided PCI strategies.
• Population Restriction: Only stable, high-risk patients were included, so caution with broader populations.

C. LITERATURE CONTEXT

• Comparisons to Previous Studies:
  • Consistent with existing evidence that combining opioids with local anesthetics can enhance analgesia without significant hypotension.
  • Addresses gaps in knowledge regarding the specific benefits of bupivacaine addition to fentanyl in thoracic epidurals.
• Guidelines and Consensus:
  • Aligns with guidelines advocating for multimodal analgesia to improve postoperative outcomes in thoracic surgery.
• Knowledge Gaps Bridged:
  • Provides evidence supporting the use of combined epidural analgesia for improved immediate postoperative pain control and oxygenation.

Clinical Application

• Impact on Practice: Routine late PCI in stable, high-risk post-MI patients does not have significant clinical benefits over optimal medical therapy alone.
• Patient Populations: Applicable to stable patients with occlusion after MI but consider individual risk profiles.
• Implementation Considerations: Medical therapy remains foundational, with individualized consideration for invasive procedures.

How To Use This Info In Practice

Practitioners should incorporate OAT’s results into treatment pathways, understanding that routine late PCI in stable, asymptomatic post-MI patients confers no major clinical benefit over optimal medical therapy and is not recommended as a blanket strategy.