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Research Article | DOI: https://doi.org/10.31579/2641-0419/416
¹Assistant professor of interventional cardiology, Department of cardiology, Tehran Heart Center, Tehran university of Medical Sciences, Tehran, Iran
²Shahroud University of medical sciences, Imam Hossein Hospital
³Student research committee, Faculty of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
⁴Department of Sports and Exercise Medicine,Imam Khomeini Hospital (Tums), Tehran, Iran
⁵Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
*Corresponding Author: Mehdi Sheibani, Department of Cardiology, Shahid Beheshti University of Medical Sciences, Loghman-hakim Hospital, kamali Avenue, South Kargar Street, Tehran, Iran.
Citation: Mohammad Sadeghian, Maryam Ahmadi, Hossein Toreyhi, Najmeh Ahmadpour, Mahshid Nazarieh, et al, (2024), No-Reflow Phenomenon after Primay Percutaneous Coronary Intervention in patients with ST segment elevation myocardial infarction treated with ticagrelor versus clopidogrel plus eptifibatide: A Randomized Clinical Trial, J Clinical Cardiology and Cardiovascular Interventions, 7(12); DOI: 10.31579/2641-0419/416
Copyright: © 2024, Mehdi Sheibani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Received: 16 September 2024 | Accepted: 30 September 2024 | Published: 21 October 2024
Keywords: no reflow phenomenon; primary percutaneous intervention; Tcagrelor; eptifibatide
Background and Aims
No reflow phenomenon (NRP) is one of the essential complications of primary percutaneous intervention (PPCI). Anti-platelets have essential role in prevention of NRP. The aim of this study is comparison the NRP between ticagrelor and clopidogrel+glycoprotein IIb/IIIa Inhibitor in ST elevation myocardial infarction (STEMI) patients candidate for PPCI.
Methods
From January 2022 to January 2023 in a randomized clinical trial we compare ticagrelor and clopidogrel plus eptifibatide (a glycoprotein IIb/IIIa inhibitor) in terms of NRP and secondary outcome include mortality, stent thrombosis, vascular complications, bleeding complications and major cardiovascular adverse events (MACE). NRP was defined as TIMI flow grade less than 3.
Results:
140 patients were randomly assigned to two study groups. Mean age of patients was 59 years and 82% were male. Baseline characteristics and culprit vessels was not significantly different between study groups.NRP at the end of procedure was occurred in 47.5% in ticagrelor group and 53.7% in clopidogrel + eptifibatide group without statistical significant difference (Pvalue: 0.48). Two major and two minor bleeding occurred in in the clopidogrel+eptifibatide group and no bleeding was reported in ticagrelor group. Bleeding complications was not significantly different between study groups. In hospital mortality, vascular complications and MACE were also not significantly different between study groups.
Conclusion:
Clopidogrel plus eptifibatide in PPCI has similar outcome with ticagrelor and could be administered if ticagrelor is unavailable or prohibited.
PPCI: Primary percutaneous intervention
STEMI: ST-segment elevation myocardial infarction
NRP: No-reflow phenomenon
GFR: glomerular filtration rate
CABG: coronary artery bypass graft surgery
ACT: activated clotting time
Primary percutaneous intervention (PPCI) is the treatment of choice recommended by the European Society of Cardiology's international guidelines to restore epicardial coronary supply in ST-segment elevation myocardial infarction (STEMI). (1) Despite significant reductions in STEMI mortality achieved through PPCI, STEMI still results in 7
Study population
This is a prospective, randomized clinical trial of patients with STEMI at Imam Khomeini Hospital in Tehran from January 2022 to January 2023. This study was approved by Medical Ethics Committee of Tehran University of Medical Sciences and registered in Iranian Registery of Clinical Trial (code: IRCT2020318046810N1). Patients with the diagnosis of STEMI whom candidate for primary PCI entered the study. Informed consent was obtained from all patients. Moreover, patients with the following conditions were excluded: patients on ticagrelor or clopidogrel, patients with cardiogenic shock, patients with CHF decompensation (NYHA class III & IV ), patients with severe valvular heart disease, patients whom referred after 12 hours of MI event based on history, patients older than 85 years old, low serum platelet count (<100>
A case report sheet includes demographic data, past medical history, cardiovascular risk factors and laboratory tests was filled for each patient. Basic ECG and ECG of 90 minutes after PCI were evaluated by a cardiologist to determine ST resolution. ST resolution was defined as at least 50
SPSS ver. 26 software was used to perform the statistical analysis of the data. The qualitative variables in the statistical study were described as percentages and ratios using descriptive indicators. A proportional statistical test with Chi-Square was also used to investigate the relationship between qualitative and qualitative variables, or if Chi-Square conditions were not met and the two-state qualitative variable was compared, the Fisher-Exact test was used. A significant level was defined as a P-value less than 0.05. Linear regression analysis was performed to examine the independent relationship of various variables with the endpoints under consideration Furthermore, as sensitivity analysis, we compare groups after excluding participants undergone thrombo-aspiration.
After considering the inclusion and exclusion criteria and receiving informed consent, 140 people were enrolled in the study, with 14 of them being excluded after randomization. Five patients excluded due to cardiogenic shock during PCI and 9 patients candidates for urgent CABG and stent implantation was not done for them (Figure 1) .Therefore, a total of 67 patients were treated with clopidogrel plus eptifibatide, and 59 patients were treated with ticagrelor.
Figure 1: Algorithm of patient selection and randomization. STEMI: ST segment Elevation Myocardial Intervention, CABG: Coronary Arteries Bypass Graft Surgery, PPCI: primary percutaneous intervention
Table 1 shows the participants' baseline characteristics. One hundred and four (82.5 %) of the participants were men. The mean [standard deviation (SD)] age of the participants was 59.13 (12.20), with no significant differences between study groups. Furthermore, the study groups had no differences in terms of basic characteristics and risk factors except mean plasma creatinine level and prevalence of type 2 diabetes mellitus (T2DM).
| Demographic information | Total (n=126) | Clopidogrel + Eptifibatide(n=67) | Ticagrelor(n=59) | P value |
| Male | 104 (82.5) | 55 (82.1%) | 49 (83.1) | 0.88** |
| Female | 22 (17.5) | 12 (17.95) | 10 (16.9) | |
| Age (years) | 59.13 (12.20) | 58.91 (11.78) | 59.38 (12.76) | 0.77 |
| - Weight (kilogram) | 77.70 (11.67) | 76.19 (12.45) | 77.81 (10.77) | 0.50 |
| - Height (centimeter) | 174.35 (55.43) | 168.87 (22.44) | 180.57 (77.30) | 0.67 |
| - BMI, (kg/m2) | 26.22 (3.52) | 25.83 (3.75) | 26.66 (3.22) | 0.45 |
| Plasma creatinine, mg/dl | 1.1 (0.26) | 1.16 (0.24) | 1.04 (0.26) | 0.017 |
| Comorbidities | ||||
| - Smoker, n (%) | 58 (46) | 29 (43.3) | 29 (49.2) | 0.51 |
| - Hypertension, n (%) | 45 (35.7) | 25 (37.3) | 20 (33.9) | 0.69 |
| - T2DM, n (%) | 30 (23.8) | 10 (14.9) | 20 (33.9) | 0.013 |
| - Opium addiction, n (%) | 29 (23) | 19 (28.4) | 10 (16.9) | 0.12 |
| - Hyperlipidemia, n (%) | 23 (18.3) | 15 (22.4) | 8 (13.6) | 0.20 |
| - IHD, n (%) | 11 (8.7) | 5 (7.5) | 6 (10.2) | 0.59 |
| - Family history of premature CVD, n (%) | 11 (8.7) | 7 (10.4) | 4 (6.8) | 0.46 |
| - History of CVA, n (%) | 2 (1.6) | 1 (1.5) | 1 (1.7) | 1 |
BMI; body mass index, T2DM; type2 diabetes mellitus, IHD; ischemic heart disease, CVD; cardiovascular disease, CVA; cerebrovascular accident *Values are shown as Mean (SD) and number (%), for continuous and categorical variables, respectively. ** Unlike other p-values, the suggested one is related to the difference between men and women. | ||||
Table 1. Baseline characteristic of the participants *.
Twenty (34%) patients in the ticagrelor group and 25(37%) patients in the clopidogrel + eptifibatide group receive morphine sulfate in the emergency room and there was no significant difference between study groups (p value: 0.69).
Table 2 illustrates the MI characteristics of the participants, including STE type based on electrocardiogram (ECG), stenotic vessels, and culprit vessels. With a prevalence of 52 (41.3%) and 32 (25.4%), respectively, the most common types of STEMI among study participants were inferior and anterior MI. Notably, no significant differences in STEMI type were found between the study groups. The LAD was the most commonly culprit vessel, accounting for 67 (53.2 percent) of total participants. In this study, a total of 226 arteries had significant obstruction with had no significant difference between two study groups. Twenty-six (20.7%) patients were single vessel disease, 72 (57.1%) were two vessel disease and 28 (22.2%) were three vessel disease. It should be noted that due to high thrombotic bulk, 13 (10.3%) patients underwent thrombo-aspiration (9 patients in clopidogrel + eptifibatide group and 4 patients in ticagrelor group) and 77 (61.1%) patients underwent pre-dilatation (46 patients in clopidogrel + eptifibatide group and 31 patients in ticagrelor group (at the discretion of the operator. Forty one patients (32.5%) was post-dilated with non-compliant balloons at the session of primary PCI due to stent under-expansion (25 patients in the Plavix + eptifibatide and 16 in the ticagrelor group). There was no difference in the number of patients who underwent this procedures between study groups (p values: 0.22, 0.06 and 0.43 for thrombo-aspiration, pre-dilation and post-dilation respectively).
| Type of STEMI | Total | Clopidogrel + Eptifibatide | Ticagrelor | P value | ||||
Anterior (V2-V4) | ||||||||
| 32 (25.4%) | 20 (29.9%) | 12(20.3%) | ||||||
Extensive anterior (V1-V6) | 21 (16.7%) | 8 (11.9%) | 13 (22.0%) | |||||
Anterolateral (V2-V4, I, aVL) | 6 (4.8%) | 5 (7.5%) | 1 (1.7%) | |||||
Extensive anterolateral (V1-V6, I, aVL) | 6 (4.8%) | 4 (6%) | 2 (3.4%) | |||||
Inferior (II, III, aVF) | 52 (41.3%) | 28 (41.8%) | 24 (40.7%) | 0.22 | ||||
Inferolateral (I, II, III, aVF, aVL) | 2 (1.6%) | 0 (0%) | 2 (3.4%) | |||||
Inferior+ RV (II, III, aVF, V4R-V6R) | 4 (3.2%) | 1 (1.5%) | 3 (5.1%) | |||||
Lateral (I, aVL, V5, V6) | 2 (1.6%) | 1 (1.5%) | 1 (1.7%) | |||||
Inferoposterior (II, III, aVF, V7-V9) | 1 (0.8%) | 0 (0%) | 1 (7%) |
| ||||
| Culprit vessels | ||||||||
| LAD | 67 (53.2%) | 38 (56.7%) | 29 (49.2%) | |||||
| RCA | 48 (38.1%) | 26 (38.8%) | 22 (37.3%) | 0.19 | ||||
| LCX | 11 (8.7%) | 3 (4.5%) | 8 (13.6%) | |||||
| Stenotic vessels * | ||||||||
| LAD | 33 (26.2%) | 17 (25.4%) | 16 (27.1%) | |||||
| LCX | 5 (4.0%) | 1 (1.5%) | 4 (6.8%) | |||||
| RCA | 16 (12.7%) | 8 (11.9%) | 8 (13.6%) | 0.30 | ||||
| LAD-LCX | 20 (15.9%) | 13 (19.4%) | 7 (11.9%) | |||||
| LAD-RCA | 18 (14.3%) | 13 (19.4%) | 5 (8.5%) | |||||
| LCX-RCA | 6 (4.8%) | 3 (4.5%) | 3 (5.1%) | |||||
| LAD-LCX-RCA | 28 (22.2%) | 12 (17.9%) | 16 (27.1%) | |||||
STEMI: ST-elevation myocardial infarction, LAD: left anterior descending artery, RCA: right coronary artery, LCX: left circumflex artery Values are shown as number (%) variables. *stenotic vessel was defined as vessels with more than 50% luminal stenosis | ||||||||
Table 2. Details of STEMI among study participant. | ||||||||
| Total | Clopidogrel + Eptifibatide | Ticagrelor | P value | |||||
| Type of STEMI | ||||||||
- Anterior (V2-V4) | 32 (25.4%) | 20 (29.9%) | 12(20.3%) | |||||
- Extensive anterior (V1-V6) | 21 (16.7%) | 8 (11.9%) | 13 (22.0%) | |||||
- Anterolateral (V2-V4, I, aVL) | 6 (4.8%) | 5 (7.5%) | 1 (1.7%) | |||||
- Extensive anterolateral (V1-V6, I, aVL) | 6 (4.8%) | 4 (6%) | 2 (3.4%) | |||||
- Inferior (II, III, aVF) | 52 (41.3%) | 28 (41.8%) | 24 (40.7%) | 0.22 | ||||
- Inferolateral (I, II, III, aVF, aVL) | 2 (1.6%) | 0 (0%) | 2 (3.4%) | |||||
- Inferior+ RV (II, III, aVF, V4R-V6R) | 4 (3.2%) | 1 (1.5%) | 3 (5.1%) | |||||
- Lateral (I, aVL, V5, V6) | 2 (1.6%) | 1 (1.5%) | 1 (1.7%) | |||||
- Inferoposterior (II, III, aVF, V7-V9) | 1 (0.8%) | 0 (0%) | 1 (7%) | |||||
| Culprit vessels | ||||||||
| - LAD | 67 (53.2%) | 38 (56.7%) | 29 (49.2%) | |||||
| - RCA | 48 (38.1%) | 26 (38.8%) | 22 (37.3%) | 0.19 | ||||
| - LCX | 11 (8.7%) | 3 (4.5%) | 8 (13.6%) | |||||
| Stenotic vessels * | ||||||||
| - LAD | 33 (26.2%) | 17 (25.4%) | 16 (27.1%) | |||||
| - LCX | 5 (4.0%) | 1 (1.5%) | 4 (6.8%) | |||||
| - RCA | 16 (12.7%) | 8 (11.9%) | 8 (13.6%) | 0.30 | ||||
| - LAD-LCX | 20 (15.9%) | 13 (19.4%) | 7 (11.9%) | |||||
| - LAD-RCA | 18 (14.3%) | 13 (19.4%) | 5 (8.5%) | |||||
| - LCX-RCA | 6 (4.8%) | 3 (4.5%) | 3 (5.1%) | |||||
| - LAD-LCX-RCA | 28 (22.2%) | 12 (17.9%) | 16 (27.1%) | |||||
STEMI: ST-elevation myocardial infarction, LAD: left anterior descending artery, RCA: right coronary artery, LCX: left circumflex artery Values are shown as number (%) variables. *stenotic vessel was defined as vessels with more than 50% luminal stenosis. | ||||||||
Table 2. Details of STEMI among study participant.
Table 3 shows continuous and categorical analysis of TIMI flow results. The mean (SD) mid-procedure TIMI flow score (after crossing the wire) for the clopidogrel + eptifibatide and ticagrelor groups was 1.88 (0.47) and 1.96 (0.41), respectively. The mean TIMI flow score in these groups at the end of the procedure (after stent implantation and post dilation if required) was 2.41 (0.60) and 2.94 (0.56), respectively. There was no significant difference between the two groups in terms of mid-TIMI flow (p-value: 0.276) or end-TIMI flow (p-value: 0.515). After crossing the wire and at the end of the procedure, 63 (94%) and 36 (53.7%) of the clopidogrel + eptifibatide group had TIMI flow scores of less than 3. Similarly, in the ticagrelor group, 55 (93.2 percent) and 28 (47.5 percent) of patients experienced mid-procedure and end-procedure no reflow phenomenon (TIMI flow < 3>(Supplementary Table3).
| Table 3. Continues and categorical analysis of TIMI flow | ||||
| Total | Clopidogrel + Eptifibatide | Ticagrelor | P value | |
| Continues | ||||
| Mid-procedure | 1.92±0.44 | 1.88±0.47 | 1.96±0.41 | 0.27 |
| End-procedure | 2.45±0.58 | 2.41±0.60 | 2.94±0.56 | 0.51 |
| Categorical | ||||
| Mid-procedure | ||||
| - 3 | 8(6.3%) | 4(6.0%) | 4(6.8%) | 1 |
| - < 3> | 118(93.7%) | 63(94.0%) | 55(93.2%) | |
| End-procedure | ||||
| - 3 | 62(49.2%) | 31(46.3%) | 31(52.5%) | 0.48 |
| - < 3> | 64(50.8%) | 36(53.7%) | 28(47.5%) | |
Values are shown as Mean (SD) and number (%), for continuous and categorical variables, respectively. Mid-procedure: after crossing the wire, end-procedure: after stent implantation | ||||
| Supplementary Table3. Continues and categorical analysis of TIMI flow after excluding patients who had undergone thrombo-aspiration | ||||
| Total | Clopidogrel + Eptifibatide | Ticagrelor | P value | |
| Mid-procedure | ||||
| - 3 | 7(6.2%) | 3(5.2%) | 4(7.3%) | 0.71 |
| - < 3> | 106(93.8%) | 55(94.8%) | 51(92.7%) | |
| End-procedure | ||||
| - 3 | 57(50.4%) | 27(46.6%) | 30(54.5%) | 0.39 |
| - < 3> | 56(49.6%) | 31(53.4%) | 25(45.5%) | |
Values are shown as Mean (SD) and number (%), for continuous and categorical variables, respectively. Mid-procedure: after crossing the wire, end-procedure: after stent implantation | ||||
Supplementary Table 3: Mid-procedure: after crossing the wire, end-procedure: after stent implantation
Given that 21 patients of the ticagrelor group whom had NRP, were treated with eptifibatide on the recommendation of the operator, secondary outcomes were compared in the three clopidogrel + eptifibatide, ticagrelor, and ticagrelor + eptifibatide groups. TIMI flow was evaluated before Eptifibatide in all patients in the ticagrelor group. The mean EF of the patients in each group after the procedure was 35.59% (10.71) in the clopidogrel + eptifibatide group, 36.57% (9.01) in the ticagrelor group, and 33.80% (12.93) in the ticagrelor + eptifibatide group. The EF differences between groups were not statistically significant (p-value: 0.79). Furthermore, the mean duration of hospitalization in the three groups was 5.83 (2.67), 5.73 (2.23), and 5.33 (2.0), with no difference between the three groups (p-value: 0.77).
Patients' post-procedure complications are illustrated in Table 4. Vascular complications occurred in two patients, one in the clopidogrel + eptifibatide group and the other in the ticagrelor group, with no statistically significant difference (p-value = 0.95). Only two people in the clopidogrel + eptifibatide group experienced major bleeding. Similarly, only two patients in the same group experienced minor bleeding. Furthermore, only one patient in the ticagrelor group experienced minimal bleeding. Bleeding requiring medical attention occurred in 2, 1, and 1 patient in the clopidogrel + eptifibatide, ticagrelor, and ticagrelor + eptifibatide groups, respectively. However, there was no significant difference in the incidence of bleeding (of any kind) between the three groups (p-value = 0.70). In the clopidogrel + eptifibatide, ticagrelor, and ticagrelor + eptifibatide groups, the incidence of MACE was 3%, 2.6%, and 9.5 %, respectively. The difference in MACE between the three groups was not statistically significant (p-value: 0.35). Stent thrombosis occurred in one patient of the ticagrelor group and no stent thrombosis occurred in other two groups.
| Total | Clopidogrel + Eptifibatide | Ticagrelor | Ticagrelor + Eptifibatide | p-value | |
| Vascular | 2 (1.6%) | 1(1.5%) | 1(2.6%) | - | 0.73 |
| Bleeding | 0.63 | ||||
| Major | 2 (1.6%) | 2 (3%) | - | - | |
| Minor | 2 (1.6%) | 2 (3%) | - | - | |
| Minimal | 1 (0.8%) | - | 1 (2.6%) | - | |
| Require medical attention | 4 (3.2%) | 2 (3%) | 1 (2.6%) | 1 (4.8%) | |
| Total | 9 (7.1%) | 6 (9.0%) | 2 (5.3%) | 1 (4.8%) | 0.70 |
| Contrast nephropathy | 10 (7.9%) | 5 (7.5%) | 3 (7.9%) | 2 (9.5%) | 0.95 |
| MACE | 5 (4%) | 2 (3%) | 1 (2.6%) | 2 (9.5%) | 0.35 |
| MACE: major adverse cardiac and cerebrovascular events | |||||
Table 4: The complications of participants after procedures during hospitalization.
The current study included 126 STEMI patients who were candidates for primary PCI and we compared them in the two groups of clopidogrel + eptifibatide and ticagrelor in terms of safety and efficacy of anti-platelet therapy. The initial characteristics of the two groups were nearly identical. The TIMI Flow findings indicate that No-reflow phenomenon does not differ significantly between these groups. Moreover, we didn’t find any difference in adverse events between study groups.
High platelet activity was seen to has association with NRP in STEMI patients.(7) Ticagrelor, as a reversible direct-acting oral antagonist of P2Y12- receptor antagonist with no catabolite activation, could have a significant impact on platelet inhibition faster and more consistently than clopidogrel. (8) The efficacy and safety of ticagrelor and clopidogrel were compared in previous studies with acceptable heterogenicity (I2 = 64%) in a meta-analysis conducted by Wang et al. (9) They found no differences in efficacy or risk of bleeding, MI, or stroke between the two groups. Another meta-analysis by Dai etal reported that loading dose of ticagrelor compare with clopidogrel effectively reduces NRP during PPCI. (10) In PLEIO study the superiority of ticagrelor to clopidogrel in recovery of endothelial function is shown .(11)In contrast to this findings a recent clinical trial showed that the incidence of NRP is not affected by the type of P2Y12Inhibitor.(12) Eptifibatide is a short-acting, small-molecule competitive inhibitor of the GP IIb/IIIa receptor. (13) The role of GP II/III inhibitors, particularly tirofiban, has always been taken into account. According to a meta-analysis of prior trials on the effect of tirofiban on TIMI flow result, it reduces the risk of thrombosis by approximately 75% and the risk of MACE by 90%. (14) A recent meta-analysis reported the effectiveness of tirofinal and eptifibatide in preventing NRP in primary PCI. (15) Given that this drug's bleeding trend did not reach a significant level, it would be a promising choice for combination therapy for ACS patients. Another meta-analysis on two common glycoprotein inhibitors, tirofiban and eptifibatide, found that treatment with tirofiban or eptifibatide had no effect on favorable outcome, functional outcome, or last available National Institutes of Health Stroke Scale (NIHSS), but may increase mortality. (16) However, considering tirofiban increased the risk of fatal ICH while decreasing the risk of ICH, maybe eptifibatide could be a better option to adjunctive therapy.
However, the efficacy of the addition of eptifibatide to clopidogrel has been examined by Moazez et al in a randomized clinical trial. (17) They suggested that platelet reactivity could be further reduced by using glycoprotein IIb/IIIa inhibitors in addition to P2Y12 inhibitors. It is worth noting that the endpoint of this study was based on laboratory measurements of platelet aggregation (PA) and activated clotting time (ACT). Because of the therapeutic dose of heparin used in this study, laboratory measurements could be easily influenced by confounding factors. The major adverse effects of combination therapy were not compared in this study, and the safety of eptifibatide should be investigated in future studies (18) To the best of our knowledge, this is the first study to compare the efficacy and safety of the eptifibatide plus clopidogrel versus ticagrelor in the total ACS population with any troponin level status.
Shimada et al evaluated whether the use of a glycoprotein IIb/IIIa inhibitor improves the relative efficacy and safety of ticagrelor when compared to clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) Trial. (19) However, no interaction was found between treatment and tirofiban use for the primary efficacy and safety end points of P2Y12 inhibitors. Moreover, stent thrombosis was found with a prevalence of about 1% in the ticagrelor group with GP IIb/IIIa inhibitor.
In our study, stent thrombosis was observed in only one case of the ticagrelor group, while the other two groups did not report any cases of MI or stent thrombosis. Due to the small number of patients, we did not have enough power to evaluate and compare stent thrombosis in different groups.
Some limitations could be considered for this study. This study was conducted in one center with 140 patients. We recommend to design a multicenter study with more cases to confirm our findings.
Clopidogrel plus eptifibatide in PPCI procedure for STEMI has similar outcomes with ticagrelor and could be administered if ticagrelor is unavailable or prohibited.
“This research received no specific grant from any funding agency in the public or commercial.
The authors declare that they have no competing interest.
All authors have read and approved the final version of the manuscript and had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.
Mehdi Sheibani affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
