This study was carried out at the Shahid Madani Heart Hospital in Tabriz, Iran from March 2020 to March 2021. The Tabriz University of Medical Sciences Ethics Committee approved the study protocol (IR.TBZMED.REC.1398.487), and written informed consent was obtained from all patients. Protocol of this trial was also registered in the Iranian Registry of Clinical Trials (IRCT: IRCT20140512017666N2, Registration date: 2019-10-15).
Study Population And Design
Patients with STEMI admitted at most 12 hours after symptom onset which underwent pPCI were enrolled in this RCT. Patients were included only if they were older than 18 years with a confirmed diagnosis of first-time STEMI a had a successful pPCI defined as post-angiographic stenosis less than 25%. STEMI was defined as at least two continuous leads with ST-segment elevation of more than 2.5 mm in males under 40, 2 mm in men over 40, or 1.5 mm in women in leads V2-V3 and/or 1 mm in the remaining leads [17]. Patients with any evidence of intimal dissection within 24 hours from admission were excluded. Other exclusion criteria were the presence or history of ventricular tachycardia or fibrillation, any kind of bundle block, previous HF or MI and history of revascularization, patients with severe valve disease, those who had contraindications for allopurinol use, patients with cardiogenic shock at the time of admission or history of previous CVA, and finally those who were candidates just for percutaneous old balloon Angioplasty (POBA). We used the results of our previous study [14] to determine the sample size. Considering α = 0.05 and a power of 80%, 80 patients in each group and a total of 160 patients were calculated for this study. One hundred eighty four individuals were initially included in the study due to the potential of missing data and attrition. Random numbers were generated using the RANDLIST 1.2 software, and patients were divided into control and intervention groups based on sample size. Before the PCI, patients in each group received either a 300 mg dose of allopurinol or a placebo. Then, for the next 28 days, 100 mg of allopurinol was given to intervention group and placebo to control group. Aspirin 325 mg and clopidogrel 300 mg were given orally, along with weight-adjusted intravenous heparin, as part of the normal pretreatment protocol for pPCI. All pPCIs were performed out by expert interventional cardiologists using the standard technique, and none of the staff members in the catheterization lab were aware of the groups.
Laboratory And Clinical Measurements
Baseline findings were recorded in all patients including demographic information like age, gender, and medical history including hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, smoking, and family history of MI. On admission, venous blood samples were taken and placed in citrated tubes with ethylenediaminetetraacetate (EDTA) potassium salt additive. The hospital laboratory received and examined blood samples. To achieve laboratory results, a daily-calibrated automated Coulter CBC H1 counter was used. Measurements were performed for hemoglobin, creatinine, uric acid, and cardiac troponin I (cTnI). During the first 48 hours of hospitalization, the blood levels of cTnI were monitored every 6 hours, and their peak values were recorded. At admission and 90 minutes after pPCI, a standard 12-lead ECG was taken, and 20 milliseconds after the end of the QRS complex, the ST-E sum was measured for the affected leads. At the time of admission and 40 days following pPCI, the left ventricle ejection fraction (LVEF) was measured echocardiographically using the modified Simpson's rule.
Follow-up
Throughout the one-year follow-up period, patients were monitored for occurrence of MACE. There were no patients lost to follow-up during the study period. Calls were made one, six, and 12 months after discharge to check on the patients. Re-hospitalizations due to HF and stroke at our hospital or other hospitals were detected and recorded through regular clinic visits. Diagnosis and assessment of HF in the hospital and clinic were done by an experienced cardiologist. Finally, patients' information during one year of follow-up was collected and compared between the control and intervention groups.
Outcomes
MACE was defined as a composite of mortality, HF, and CVA during hospitalization and follow-up. The principal aim of the study was to evaluate the effect of allopurinol use on one-year MACE. Comparison of HF, CVA, and mortality alone between two groups during the follow-up period was the secondary outcome of this study.
Statistical Analysis
All statistical analyses were conducted using SPSS (Version 21.0; IBM SPSS Corporation, Chicago, IL). The Kolmogorov-Smirnov test was used to verify the normal distribution assumption for continuous data. While qualitative data were provided as frequency and percent (%), quantitative data were shown as mean (SD) when parametric tests were employed and as median (interquartile range) when nonparametric tests were used. For normally distributed continuous variables, an independent samples t-test was utilized, and for nonparametric data, a Mann- Whitney U test. The Fisher's exact test or the chi-square test, as appropriate, was used to analyze categorical variables. Calculations were made to determine relative risks (RR) and their confidence intervals. The Kaplan-Meier curve was used in survival analysis to compare the mortality and follow-up MACE between the two groups. P-values < 0.05 were considered statistically significant.