Primary percutaneous coronary intervention (PCI) is the gold standard for reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI), as it restores blood flow by clearing the blocked coronary artery. This process helps reoxygenate the previously hypoxic myocardium, potentially preventing further myocardial cell death. However, despite its benefits, reperfusion therapy, including primary PCI, can also lead to reperfusion injury, which may worsen myocardial damage, increase infarct size, and negatively impact patient outcomes. One of the key contributors to reperfusion injury is reactive oxygen species (ROS), which can induce oncosis, necrosis, and apoptosis, ultimately promoting cell death, myocardial remodeling, left ventricular systolic dysfunction and poorer clinical outcomes. N-Acetylcysteine (NAC), widely known for its mucolytic properties, has also been recognized for its antioxidant and cardioprotective effects. By reducing oxidative stress, NAC has been shown to decrease oncosis, necrosis, and apoptosis, as evidenced by lower levels of malondialdehyde, IL-6, troponin, caspase-3, and major adverse cardiac events in STEMI patients. However, existing research on NAC has only explored oral and intravenous administration. Given that reperfusion injury occurs rapidly, an optimal approach would involve delivering cardioprotective agents directly to the target site, specifically coronary artery endothelial cells. To date, no studies have directly investigated the effects of intracoronary NAC administration in STEMI patients undergoing primary PCI.

This study is a double-blind, randomized controlled trial, single-center study in STEMI patients undergoing primary PCI patients held in Moewardi General Hospital, Central Java, Indonesia. The investigator divided 70 patients with STEMI into two groups, the first is the NAC group, which will get 480 mg of intracoronary NAC immediately after the lesion is opened during primary PCI is performed and the second group will have a normal saline bolus. Each patient will be checked for malondialdehyde, IL-6, hs-troponin I, and caspase-3 just before the primary PCI is performed and 24 hours after intervention. GLS examinations were carried out at admission, discharge, and 6 months after the intervention. The 6MWT examinations were conducted at 1 week and 6 months after the intervention. Furthermore, researchers recorded data on all-cause mortality, rehospitalization, and ACS recurrence at day 30 and 6 months. The study was approved by the hospital ethics committee. The clinical parameters above will then be analyzed. To determine the mean difference between each group (intervention and control) before and after treatment a paired T-test is used if the data distribution is normal (if not, the Wilcoxon test is used). To determine the mean difference between unpaired groups (treatment and control), an independent T-test is used if the distribution is normal (if not, the Mann-Whitney test is used). Normality testing is performed using the Shapiro-Wilk test, considering the sample size is less than 50 per group.

Inclusion Criteria:

1. STEMI patients according to The Fourth Universal Definition of Myocardial Infarction from the European Society of Cardiology, American College of Cardiology, American Heart Association, and World Heart Federation Treated by Primary PCI.
2. Aged 30-60 years
3. Willing to participate in the study and sign informed consent.

Exclusion Criteria:

1. Patients with cardiogenic shock (SBP ≤ 80 mmHg, cold extremities, urine output <0.5 ml/kg/hour) <24 hours before randomization
2. Patients with a history of myocardial infarction
3. Patients with a history of chronic heart failure before the onset of AMI
4. Patients scheduled for coronary artery bypass surgery
5. Patients with chronic renal failure or requiring dialysis
6. Patients with chronic inflammation
7. Patients with malignancy
8. Patients with a history of hyper/hypothyroidism
9. Patients with acute infection
10. Patients with sepsis
11. Patients with acute stroke
12. Patients with pulmonary fibrosis
13. Patients with a history of autoimmune disease
14. Patients with a history of anti-inflammatory / antioxidant supplementation
15. Patients with allergy to N-acetylcysteine
16. Pregnant and lactating patients

This study was conducted as part of the final project for doctoral program, there was no sponsorship during this study therefore the IPD cannot be shared