In this study, we randomized 413 diabetic patients with STEMI who presented within 12 hours of symptoms onset and underwent primary PCI between December 2016 and May 2019 in 5 different centers. We enrolled patients during this specified recruitment period, thus a sample size calculation was not performed. Patients were randomly assigned to either group using a block randomization. Diabetes was diagnosed, by history and/or according to American Diabetes Association, based on a fasting plasma glucose ≥ 126 mg/dL, a random plasma glucose ≥ 200 mg/dL plus associated symptoms of hyperglycemia or a HbA1c level ≥ 6.5%.16

The exclusion criteria included: use of a fibrinolytic agent within 14 days before PCI, suspected active internal bleeding, history of cerebrovascular accident within the previous 2 years or known platelet count <100 000 cells/μl, TIMI flow grade ≥ 2 or thrombus grade ≤ 2 and cardiogenic shock.

Before PCI, only patients with large angiographic thrombus burden (grade ≥ 3) and planned for aspiration thrombectomy to reduce the thrombus burden according to the operator's discretion were eligible for enrollment. Patients were randomized to either thrombus aspiration alone (using Export Aspiration Catheter; Medtronic, United States) (n=207) or to receive local delivery of 180 μg/kg intracoronary eptifibatide plus 100 μg verapamil and 100 μg nitroglycerin given via thrombus aspiration with ≤ 5cc contrast to visualize the distal bed (n=206). After aspiration, the thrombectomy catheter was removed from the vessel, flushed with heparinized saline and subsequently re-introduced into the culprit vessel distal to the occlusion, prior to the selective administration of intracoronary drugs. The drugs were infused into the infarct-related artery after visualization of the distal bed with minimal amount of contrast following aspiration (figure 1). Conversely, balloon predilatation was permitted if thrombus aspiration was ineffective according to operator decision. In case of multivessel involvement, the infarct-related artery was treated first, and complete revascularization was performed in another session during hospital stay.

Figure 1.

Injection of contrast via the aspiration catheter for visualization of the distal bed in 2 different patients.

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All patients were treated with drug eluting stent of the culprit lesion. All patients received weight adjusted dose of heparin during the procedure, dual antiplatelet therapy; aspirin 300 mg orally on presentation, ticagrelor 180 mg or clopidogrel 600 mg loading dose before PCI followed by daily maintenance dose for 1 year after stent implantation.

Routine laboratory investigations were done for all patients including cardiac biomarkers; high sensitivity troponin on admission and 6 hours after, creatinine phosphokinase (CK), CK-MB levels every 6 hours till normalization, serum creatinine level, complete blood picture on admission and daily until discharge. Echocardiography was reviewed by experienced, blinded operators during the index hospitalization and at 6 months to assess left ventricular ejection fraction (EF) using Simpson's method.

Before inclusion, informed written consent was obtained from each patient and the study protocol was reviewed and approved by institutional human research committee. Moreover, the protection of the privacy of the participants was ensured, as well as the confidentiality of the research data.

The primary endpoints were postprocedural assessment of myocardial blush grade (MBG), postprocedural TIMI flow, and corrected TIMI frame count (cTFC). The secondary endpoints were 6-month rates of major adverse cardiac events (MACE); defined as all-cause mortality, recurrent MI, or target vessel revascularization during routine clinic visit assessment or by scheduled phone calls. Left ventricular EF was re-assessed at the end of the follow-up when MACE was analyzed.

TIMI thrombus grading classification was used to evaluate thrombus burden. Patients were considered to have angiographically evident thrombus if TIMI thrombus grade ≥ 3. Both TIMI flow and MBG were graded on the coronary angiogram with duration of cine filming at least 3 cardiac cycles to make sure that the entire washout phase was included. MBG was assessed during the same phase of the cardiac cycle. MBG and other quantitative coronary angiography parameters were measured and analyzed off-line by an interventional cardiologist who was blinded of the treatment assignment.

The collected data were coded, tabulated, and statistically analyzed using IBM SPSS statistics (Statistical Package for Social Sciences) software version 22.0 (2013, IBM Corp., United States). Inferential analyses were performed for quantitative variables, independent Student t-test in cases of 2 independent groups with normally distributed data. In qualitative data, inferential analyses for independent variables were done using chi-square test for differences between proportions and Fisher's exact test for variables with small expected numbers. Descriptive statistics was performed for quantitative data as means±standard deviation since the data were normally distributed data, while qualitative data were presented as number and percentage. The level of significance was set at P-value <.05 is significant, otherwise was considered nonsignificant.

During the study period, 413 patients who presented with acute STEMI, and planned for primary PCI were included in the study (figure 2). After angiographic confirmation of high thrombus burden, patients were randomized to either distal intracoronary injection of eptifibatide, verapamil and nitroglycerin through aspiration catheter after thrombus aspiration (n=206), or thrombus aspiration alone (n=207). The baseline demographic data, including age, sex and cardiovascular risk factors and infarct-related vessel is presented in table 1.

Figure 2.

Patient flow diagram. IC, intracoronary; STEMI, ST-segment elevation myocardial infarction.

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In the intracoronary eptifibatide and vasodilators group, the peak CK-MB reached was 217.53±81.32, vs 364.17±157.12 in the thrombus aspiration alone group (P=.001). And the mean time to reach peak of CK-MB was 11.38±4.83 hours in the local intracoronary eptifibatide and vasodilators group, and 19.54±9.21hours in the thrombus aspiration alone group (P=.001).

There was no difference in the rates of ST resolution (mean value of 58.2%±13.91 in intracoronary eptifibatide and vasodilators group vs 52.7%±26.5 in the thrombus aspiration alone group, P=.40) (table 2).

Echo was performed on all patients before discharge, ejection fraction measured postinfarction was 46.9±6.36% in the intracoronary eptifibatide and vasodilators group vs 39.3±5.12% in the thrombus aspiration alone group, P=.005. Quantitative coronary angiography results are shown in table 3.

There was a significant increase in number of patients with MBG 3 in the intracoronary eptifibatide and vasodilators group compared with the thrombus aspiration alone group was observed (80.5% vs 31.8% P=.001) and shorter cTFC (18.16±6.54 vs 29.64±5.53, P=.001). The intracoronary eptifibatide and vasodilators group had higher rates in achievement of TIMI 3 (91.3% vs 61.65%; P=.005). The rates of MACE were not statistically different between both groups (P> .05). One patient died in the intracoronary eptifibatide and vasodilators group during hospital stay, as well as in the thrombus aspiration alone group. Only one patient in thrombus aspiration alone group required revascularization in the infarct-related vessel after 2 months. There was no difference in the rates of procedure related complications, major or minor bleeding, or significant change in platelet count in both arms. EF was better at 6-month in the intracoronary eptifibatide and vasodilators (55.2±8.13 vs 43±6.67; P=.005) (table 4).

The findings of this study should be interpreted in the context of some limitations. First, inclusion of only diabetic patients would make our findings not generalizable to all-comers with STEMI undergoing primary PCI. Second, we were unable to discern whether the improvement in the primary endpoint is due to the combination of the GPI and vasodilators or whether this improvement may be due only to one of the two components separately. Third, the sample size and relatively short duration of follow-up likely contributed to the low number of clinical events. Fourth, while the assessment of the angiographic outcomes was blinded, the assessment of the clinical endpoints was not. Fifth, this study was not placebo-controlled which could reduce the comparability of both arms. Finally, benefits such as ability to perform direct stenting or reduced stent length were not examined.