Effect of Postconditioning on Myocardial Reperfusion During Primary Percutaneous Coronary Intervention - POST

Description:

Ischemic postconditioning is repetitive reversible ischemia during early reperfusion after the prolonged ischemic insult. Animal studies have demonstrated that postconditioning has cardioprotective effects that are comparable to preconditioning. The current trial sought to test the safety and efficacy of ischemic postconditioning in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Hypothesis:

Ischemic postconditioning would be associated with improved myocardial perfusion in patients with STEMI undergoing primary PCI.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • ST-segment elevation >1 mm in two or more contiguous leads
  • The presence of chest pain for <12 hours after symptom onset
  • TIMI flow grade 0 or 1 in the infarct-related artery
  • Target lesion in a native coronary vessel with reference diameter of 2.25-4.25 mm

    Number of enrollees: 700
    Duration of follow-up: 1 month
    Mean patient age: 46 years
    Percentage female: 23%
    Ejection fraction: 50.1%

Exclusions:

  • Hemodynamic instability or cardiogenic shock
  • Left bundle branch block on electrocardiogram
  • Left main lesion
  • Rescue PCI after thrombolysis or facilitated PCI
  • Noncardiac comorbid conditions with life expectancy <1 year or that may result in protocol noncompliance (per site investigator’s medical judgment)
  • Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study

Primary Endpoints:

  • Complete (STR >70%) at 30 minutes after the procedure

Secondary Endpoints:

  • TIMI flow grade after PCI
  • Myocardial blush grade
  • MACE (a composite of death, reinfarction, severe heart failure, or stent thrombosis) at 30 days
  • Each component of MACE at 30 days
  • Target vessel revascularization at 30 days

Drug/Procedures Used:

Before the PCI procedure, all patients received 300 mg of aspirin and 600 mg of clopidogrel as loading doses. Patients were randomized in a 1:1 fashion to postconditioning following primary PCI or routine primary PCI. In the postconditioning group, immediately after restoration (Thrombolysis in Myocardial Infarction [TIMI] grade ≥2) of coronary flow (without regard to method of restoration), an angioplasty balloon was positioned at the culprit lesion or stented segment and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each instance of inflation separated by 1 minute of reflow. Thrombus aspiration, predilation before stenting, or use of glycoprotein IIb/IIIa inhibitors was left to the operators’ discretion.

Concomitant Medications:

Thrombus aspiration (47%), IIb/IIIa inhibitor use (23%)

Principal Findings:

A total of 700 patients were randomized, 350 to postconditioning and 350 to conventional PCI. Baseline characteristics were fairly similar between the two arms. About 25% had diabetes, 52% were current smokers, and 2% had prior MI. The left anterior descending artery was the infarct-related vessel in 46% of the patients, and the right coronary artery in 43%. Baseline TIMI flow before PCI was 0/1 in 96% of patients. The mean ischemic time was about 196 minutes. Direct stenting was utilized in 13% of the patients.

The primary endpoint of complete ST-segment resolution (STR) at 30 minutes was similar between the postconditioning and conventional PCI arms (40.5% vs. 41.5%, p = 0.79). Other reperfusion markers such as TIMI myocardial blush grade 3 (51.9% vs. 47.1%, p = 0.20) and TIMI 3 flow post-PCI (92% vs. 87.9%, p = 0.08) were similar between the two arms. Clinical outcomes at 1 month including major adverse cardiac events (MACE) (4.3% vs. 3.7%, p = 0.70), all-cause mortality (3.7% vs. 2.9%, p = 0.53), reinfarction (0.6% vs. 0.3, p = 0.99), and stent thrombosis (2% vs. 1.7%, p = 0.78) were similar between the two arms.

Interpretation:

The results of the POST trial indicate that postconditioning (with short bursts of balloon occlusion immediately after establishing perfusion) is not superior to conventional primary PCI in patients with STEMI. There have been several smaller trials on postconditioning in patients presenting with STEMI with mixed results. This is one of the larger trials on this topic and demonstrates no difference between the two arms. The method of inducing postconditioning has, however, been different between the numerous studies, and the best protocol for this remains unclear.

References:

Presented by Dr. Joo-Yong Hahn at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2012), Miami, FL, October 25, 2012.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Ticlopidine, Angioplasty, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Stents, Thrombosis, Chest Pain, Balloon Occlusion, Ischemic Postconditioning, Diabetes Mellitus


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