Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary Percutaneous Coronary Intervention on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute Myocardial Infarction - Effect of Complementary Intracoronary Streptokinase Administration Immediately After Primary PCI on Microvascular Perfusion and Late Term Infarct Size in Patients With Acute MI

Description:

Intracoronary streptokinase (ICSK) has been shown to be associated with improved microperfusion in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). The current trial sought to study effects of ICSK on intermediate-term parameters in patients with STEMI.

Hypothesis:

ICSK would be associated with reduced infarct size and better left ventricular (LV) volumes and functions, as compared with no therapy at 6 months.

Study Design

Study Design:

Patients Screened: 188
Patients Enrolled: 95
Mean Follow Up: 6 months
Mean Patient Age: 52.5 years (ICSK), 57.8 years (control)
Female: 14

Patient Populations:

  • Primary PCI within 12 hours of STEMI

Exclusions:

  • History of prior MI
  • TIMI flow grade II/III down IRA
  • Culprit lesion in saphenous vein graft
  • Left bundle branch block

Primary Endpoints:

  • LV infarct size at 6 months

Secondary Endpoints:

  • LV volumes and functions
  • Major adverse cardiac events (death, MI, revascularization)

Drug/Procedures Used:

Immediately after diagnostic angiography, eligible patients were assigned to either the ICSK or the control group. In the ICSK group, immediately after recanalizing the infarct-related artery (IRA), 250 kU of streptokinase diluted with 20 ml of saline was infused through the guiding catheter within 3 minutes. The control group received no additional therapy.

Concomitant Medications:

All patients received aspirin 300 mg, clopidogrel as a loading dose of 600 mg, intracoronary unfractionated heparin at a dose of 100 U/kg, and tirofiban as a bolus of 0.1 µg/kg in 3 minutes, followed by a continuous infusion of 0.15 µg/kg/min for 12 hours. Other medications: beta-blockers (89%), statins (95%), and angiotensin-converting enzyme inhibitors (87%).

Principal Findings:

A total of 95 patients were randomized, 51 to ICSK and 44 to the control arm. Baseline characteristics were fairly similar between the two arms, except age (52.5 vs. 57.8 years), diabetes (8% vs. 23%), and time from pain to balloon inflation (249.2 vs. 177.5 minutes) in the ICSK arm compared with placebo, respectively. About 60% of the STEMIs were anterior, and about 40% had evidence of multivessel disease. Recognized side branch embolization occurred in 7% of the patients.

There was no difference in corrected TIMI frame count (cTFC) (29.9 vs. 31.2, p = 0.52) between the ICSK and control groups immediately post-PCI. However, this was significantly lower in the ICSK arm at 2 days (20.7 vs. 29.2, p < 0.001) and at 6 months (19.4 vs. 27.9, p < 0.001). Myocardial blush grade (MBG) 2/3 was higher in the ICSK arm immediately post-PCI (40% vs. 18%, p = 0.04), on the second day (86% vs. 36%, p < 0.001), and at 6 months (97% vs. 67%, p < 0.001). ST-segment resolution 90 minutes after reperfusion was similar between the two arms (70.0 vs. 61.2, p = 0.14).

At 6 months, LV end-systolic volume (41.1 vs. 60.9 ml, p = 0.009), LV end-diastolic volume (95.5 vs. 118.3 ml, p = 0.006), LV ejection fraction (EF) (57.2% vs. 51.8%, p = 0.02), and infarct size (22.7% vs. 32.9%, p = 0.003) were all significantly better in the ICSK arm, as compared with the control arm. Overall mortality (3.9% vs. 6.8%, p = NS) and reinfarction (2% vs. 0%, p = NS) were similar between the ICSK and control arms, respectively. The number of bleeding episodes was similar between the two arms.

Interpretation:

The results of this small trial indicate that ICSK is associated with improved parameters of myocardial tissue perfusion (cTFC and MBG), as well as improved LV indices such as LV end-systolic dimension, LV end-diastolic volume, LVEF, and infarct size at 6 months, highlighting the importance of tissue level perfusion after epicardial perfusion in patients presenting with STEMI. However, there was no difference in clinical outcomes between the two arms. Larger studies with long-term follow-up of clinical outcomes are necessary before this approach can be considered for routine use in patients with STEMI undergoing primary angioplasty.

References:

Sezer M, Cimen A, Aslanger E, et al. Effect of intracoronary streptokinase administered immediately after primary percutaneous coronary intervention on long-term left ventricular infarct size, volumes, and function. J Am Coll Cardiol 2009;54:1065-71.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Streptokinase, Pain, Angioplasty, Balloon, Coronary, Diabetes Mellitus, Percutaneous Coronary Intervention


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