A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in Patients Undergoing Pharmaco-invasive Reperfusion Early After an ST-segment Elevation Myocardial Infarction

• Author / Creator

  Mathew, Anoop

• Background: N-acetyl cysteine (NAC) effectively breaks down arterial thrombi in animal models and activates cardioprotective cellular pathways in STEMI models. Our study aimed to conduct a pilot trial to translate the beneficial effects of intravenous NAC observed in vascular occlusion models into clinical practice.
  Objective: The objective was to evaluate the extent of myocardial salvage achieved through early administration of intravenous high-dose NAC in high-risk STEMI patients with a substantial area of myocardium at risk, in comparison to standard therapy.
  Methods: This investigator-initiated, single-center, open-label trial involved the randomization of high-risk STEMI patients undergoing pharmaco-invasive reperfusion. Participants were assigned to receive either intravenous high-dose NAC or standard therapy. The primary clinical endpoint was the measurement of myocardial infarction size using late gadolinium-enhanced cardiac magnetic resonance imaging. The investigators responsible for assessing the primary study outcome remained blinded to the randomization.
  Results: A total of 44 patients were randomized, with 22 patients assigned to the intravenous NAC group and 22 patients to the control group. All patients received thrombolytic therapy prior to reaching PCI-capable hospital, with a mean (SD) symptom-to-needle time of 1.5 (± 0.7) hours. There was no significant difference in myocardial infarct size between the two groups (mean [SD] infarct size as a percentage of LV myocardial mass: intravenous NAC: 19.7 [7.9] % versus control: 18.2 [10.1] %, p = 0.62). LV volumetric measurements, including LV end-diastolic volume index (intravenous NAC: 75.6 [17.5] ml/m2 versus control: 71.7[14.1] ml/m2, p = 0.78) and end-systolic volume index (intravenous NAC: 38.7 [11.7] ml/m2 versus control: 35.4 [9.5] ml/m2, p = 0.83), were similar between the two groups. Two patients in the intravenous NAC group developed congestive heart failure. Myocardial microvascular obstruction was present in 6 (37.5%) patients in the intravenous NAC arm and 9 (42.9%) patients in the standard therapy arm (p = 0.74). There was no significant difference in myocardial salvage between the groups (intravenous NAC: 18.4 [7.2] % versus control: 18.4 [6.0] %, p = 0.99).
  Conclusions: High-dose intravenous NAC administration did not lead to a reduction in myocardial infarct size in high-risk patients undergoing early reperfusion with a pharmaco-invasive strategy following a STEMI with a significant area of myocardium at risk. In conclusion, the translation of cardioprotective therapies from animal studies to clinical care for STEMI patients continues to pose significant challenges. However, this pilot randomized trial, which adheres to current translational research guidelines, stands as a valuable model for designing future trials aimed at evaluating cardioprotective therapies within the context of STEMI.

• Subjects / Keywords

  • ST Elevation Myocardial Infarction
  • Acetylcysteine
  • Myocardial Reperfusion

• Graduation date

  Fall 2023

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-j720-4e53

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.