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*Corresponding Author: Kun Lian, Xijing Hospital, Airforce Military Medical University, China, Chengxiang Li, Xijing Hospital, Airforce Military Medical University, China and Qingyi Wang, School of Basic Medicine, Airforce Military Medical University, China.
Citation: Peng Han, Ying Liang, Suining Xu, Shuai Zhao, Yan Chen. et all (2022). Ticagrelor Versus Clopidogrel in the treatment of Elderly Chinese Chronic Total Occlusion Patients Undergoing Percutaneous Coronary Intervention. J. Clinical Cardiology and Cardiovascular Interventions, 5(4); DOI:10.31579/2641-0419/259
Copyright: © 2022 Kun Lian, Chengxiang Li and Qingyi Wang, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 08 March 2022 | Accepted: 14 March 2022 | Published: 21 March 2022
Keywords: ticagrelor; clopidogrel; aged cto patients; percutaneous coronary intervention; chronic total occlusion
Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients.
Objective: This study was designed to investigate the effectiveness and safety of Ticagrelor in comparison with Clopidogrel as an add-on therapy to Aspirin for elderly Chinese CTO patients who underwent elective PCI.
Materials and Methods: We retrospectively enrolled 504 CTO patients (aged ≥75 years) who received PCI from December 2009 to May 2020 and DAPT for up to 12 months. The effectiveness endpoints were evaluated by major adverse cardiac events (MACE) including all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding.
Results: Patients in Clopidogrel group, as was evidenced in our study, were older, and had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) showed no significant difference. After clinical characteristics balanced matching by inverse probability of treatment weighting (IPTW) model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTW model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006).
Conclusions: Clopidogrel and Ticagrelor present similar effectiveness and safety to elderly Chinese CTO-PCI patients, yet Ticagrelor should be prescribed with caution to patients with a high bleeding risk.
Coronary chronic total occlusion (CTO) is observed in approximately 15-25% of coronary artery disease (CAD) patients who underwent prior coronary angiography [1,2]. Guidelines recommend selective percutaneous coronary intervention (PCI) to CTO patients to improve their symptoms and quality of life, as well as survival rates [3,4]. Intensive dual antiplatelet therapy (DAPT) is recommended for CTO-PCI patients to reduce potential thrombosis induced by complex lesions and frequent stent placement of CTO [5,6]. Tough continuous antiplatelet therapy is also associated with increased bleeding, more concern is given for delivering DAPT medication to elderly CTO-PCI patients to balance bleeding and ischemia, as the elderly population over 75 years has a much higher risk of bleeding. Nevertheless, given that traditional clinical randomized controlled trials seldom had elderly CTO patients as their subjects, data on elderly CTO-PCI patients’ DAPT is scarcely available.
As the most commonly used DAPT drugs, Ticagrelor has faster action and stronger antiplatelet effect, and its effect is reversible compared with Clopidogrel [7]. Chinese CTO-PCI patients were reportedly showed lower MACE incidence and higher bleeding incidence after receiving normal dose of Ticagrelor, compared with Clopidogrel in Chinese CTO-PCI patients [8],. Unfortunately, no data concerning the elderly patients was found.
Considering the profound potential value of identifying how different DAPT strategies affect elderly CTO-PCI patients, this study was designed to investigate the effectiveness and safety of Ticagrelor in comparison with Clopidogrel as an add-on therapy to Aspirin for elderly Chinese CTO patients who received PCI.
Study design
This study was conducted in the Department of Cardiology, Xijing Hospital from December 2009 to May 2020 and aimed to compare the effectiveness and safety of Ticagrelor versus Clopidogrel in elderly Chinese CTO patients who underwent elective PCI with drug-eluting stents (DES). PCI success was assessed by the interventional cardiologist performing the procedure. The study protocol was approved by the Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants.
Study participants
From December 2009 to May 2020, a total of 504 CTO patients who successfully underwent elective PCI were prescribed DAPT for up to 12 months, and were retrospectively enrolled in the study. Among the 504 patients, with 30 lost in follow-up, eventually 474 patients were included in this study. These patients were initiated on DAPT prior to PCI, among whom 320 took Clopidogrel with a 300mg loading dose followed by a dose of 75 mg daily, while the other 154 patients took Ticagrelor with a loading dose of 180 mg followed by a dose of 90 mg twice daily. All the patients took Aspirin at a dose of 100 mg daily. Inclusion criteria included: 1) were aged ≥75 years old; 2) validated with CTO by coronary angiography; 3) received PCI successfully; 4) signed the informed consent. Exclusion criteria included: 1) underwent conservative oral anticoagulation therapy; 2) exhibited PCI contraindications; 3) displayed P2Y12 inhibitors contraindications; 4) with high risk of bleeding diathesis or coagulation disorder; 5) diagnosed with dialysis-dependent renal failure or liver cirrhosis; 6) refused to participate in this study by the patient. Clinical baseline, angiographic and procedural data were collected and recorded.
Study endpoints and definitions
Clinical follow-up was carried out by telephone interviews and outpatient visits. The follow-up period started from the date of DAPT use after PCI and ended when any study outcome first occurred or at 12 months after PCI. Inpatient observation and outpatient visits were scheduled for patients being regularly followed up in our hospital, while telephone calls were made for patients without regular medical follow-up. The incidence of end points was collected in medical records by a predefined questionnaire, in which health status, physical examinations, vital signs as well as laboratory assessments were simultaneously recorded. The effectiveness endpoints in this study were evaluated by the occurrence of MACE, i.e., the composite of all-cause death, nonfatal MI and clinically driven revascularization. All-cause death was defined as death from any cause, which was ascertained without adjudication [9].
CTO was defined as angiographic evidence of total occlusion with complete interruption of anterograde blood flow (Thrombolysis In Myocardial Infarction (TIMI) flow grade 0) with an estimated duration of＞3 months via previous angiograms, angina symptoms and a history of MI [2]. Coronary arteries measured were proximal left main artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). The diagnosis of MI was based on the Fourth Universal Definition of MI [10]. Clinically driven revascularization was defined as any reintervention because of symptoms [11]. The safety endpoints were evaluated by the incidence of bleeding: Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 [12]. Type 1 is inactive bleeding. Type 2 is active bleeding requiring evaluation or intervention by medical personnel, which differs from Type 3, Type 5 and bleeding related to coronary artery bypass graft. Type 3 is heavy bleeding as well as intracranial bleeding with significant hemoglobin reduction to 5g/dl, which requires blood transfusion. For Type 5, it refers to potential or qualitative fatal bleeding. The major bleeding events, which are the equivalent of BARC 3 and 5, include gastrointestinal bleeding, intracranial hemorrhage, hemoglobin decrease of ≥3 g/dL, significant bleeding requiring blood transfusion, and fatal bleeding [13].
Statistical analysis
This is a single-center, retrospective cohort study. Continuous variable was described as mean ± SD or median and interquartile spacing, and categorical variable as number (percentage). Differences in continuous and categorical variables between groups were analyzed with Mann–Whitney U-test and Chi-square test respectively, and P< 0>
Clinical baseline, angiographic and procedural baseline characteristics
In this study, a total of 504 CTO patients (≥75 years) were prescribed with DAPT for 12 months after PCI from December 2009 to May 2020. During this period of time (12 months after PCI), 30 patients were lost to follow-up, and in the end 474 CTO patients were included in the study (Figure 1).
In terms of clinical baseline characteristics, compared with the patients in Ticagrelor group, those in Clopidogrel group were older (80.45±4.23 vs. 79.18±3.59, P=0.001) and had a higher percentage of BMI (24.14±3.49 vs. 22.82±4.75, P=0.003), more elevated diastolic blood pressure (74.53±10.16 vs. 71.82±9.85, P=0.007) and higher HDL-C (1.92±0.87 vs. 1.05±0.29, P<0>P<0> P=0.003), and they had lower glucose (24.14±3.49 vs. 22.82±4.75, P=0.003), TG (1.31±0.78 vs. 1.48±0.85, P=0.037) and LDL-C (1.22±0.71 vs. 1.96±0.75, P<0>P＞0.05 for all) (Table 1).
| Variable | Clopidogrel (n=320) | Ticagrelor (n=154) | P value |
|---|---|---|---|
| Age, years | 80.45±4.23 | 79.18±3.59 | 0.001 |
| Male, % | 230 (71.88) | 115 (74.68) | 0.582 |
| BMI | 24.14±3.49 | 22.82±4.75 | 0.003 |
| Heart rate, beats/min | 73.15 ±12.33 | 72.24±10.74 | 0.437 |
| SBP, mmHg | 130.02±22.71 | 128.39±25.38 | 0.487 |
| DBP, mmHg | 74.53±10.16 | 71.82±9.85 | 0.007 |
| Smoking, % | 87 (27.19) | 33 (21.43) | 0.215 |
| Medical history | |||
| Hypertension, % | 192 (60.00) | 85 (55.19) | 0.322 |
| Diabetes mellitus, % | 90 (28.13) | 48 (31.17) | 0.518 |
| Hyperlipidemia | 72(22.50) | 67 (43.51) | <0> |
| Valvular heart disease, % | 2 (0.63) | 0 | 1.000 |
| Atrial fibrillation, % | 12 (375) | 4 (2.60) | 0.598 |
| Stroke, % | 33 (10.31) | 19 (12.34) | 0.532 |
| Chronic kidney diseases, % | 8 (2.50) | 8 (5.19) | 0.172 |
| Peripheral arterial disease, % | 2 (0.63) | 0 | 1.000 |
| Family history of CAD, % | 0 | 2 (1.30) | 0.105 |
| Prior MI, % | 15 (4.69) | 10 (6.49) | 0.511 |
| Prior PCI, % | 82 (25.63) | 61 (39.61) | 0.003 |
| Prior CABG, % | 8 (2.50) | 2 (1.30) | 0. 511 |
| Laboratory data before PCI | |||
| WBC (109/L) | 6.65±2.19 | 6.87±3.79 | 0.420 |
| RBC (1012/L) | 4.24±0.61 | 4.24±0.53 | 0.946 |
| Hb (g/L) | 131.19±18.45 | 129.87±17.01 | 0.457 |
| PLT (109/L) | 177.32±67.05 | 189.04±60.24 | 0.066 |
| Creatinine (μmol/L) | 108.20±52.01 | 114.93±82.86 | 0.288 |
| Ccr (ml/min) | 49.09±13.88 | 46.40±13.54 | 0.104 |
| BUN (mmol/L) | 5.89±2.20 | 6.06±1.97 | 0.655 |
| UA (μmol/L) | 311.00±289.95 | 313.27±89.20 | 0.930 |
| ALT (U/L) | 20.00 (16.75) | 21.00 (11.00) | 0.578 |
| AST (U/L) | 20.00 (13.00) | 16.00 (12.85) | 0.177 |
| Alb (g/L) | 38.49±4.99 | 37.96±3.94 | 0.363 |
| Glu (mmol/L) | 6.19±2.42 | 6.97±3.04 | 0.007 |
| TC (mmol/L) | 3.64±1.07 | 3.52±0.89 | 0.236 |
| TG (mmol/L) | 1.31±0.78 | 1.48±0.85 | 0.037 |
| LDL-C(mmol/L) | 1.22±0.71 | 1.96±0.75 | <0> |
| HDL-C(mmol/L) | 1.92±0.87 | 1.05±0.29 | <0> |
| NT-proBNP (pg/ml) | 598.30 (1415.98) | 661.50 (2065.50) | 0.229 |
| LVEF (%) | 52.17±9.36 | 51.12±9.29 | 0.303 |
Abbreviations: CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; BMI, Body Mass Index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; Hb, Hemoglobin; PLT, blood platelet; Ccr, creatinine clearance; BUN, blood urea nitrogen; UA, uric acid; ALT, alanine amiotransferase; AST, aspartate aminotransferase; Alb, albumin; Glu, Glucose; TC, triglyceride; TG, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction.
Table 1: Clinical baseline characteristics (n=474)
For CTO lesion characteristics, no significant differences were found as to the CTO lesions of coronary arteries (LM, LAD, RCA, and LCX), number of treated vessels, number of stents or total stent length (P＞0.05 for all) (Table 2).
| Variable | Clopidogrel (n=320) | Ticagrelor (n=154) | P value |
|---|---|---|---|
| CTO Lesion characteristics, % | |||
| LM | 2 (0.63) | 0 | 1.000 |
| RCA | 149 (46.56) | 76 (49.35) | 0.624 |
| LAD | 158 (49.38) | 71 (46.10) | 0.556 |
| LCX | 96 (30.00) | 53 (34.42) | 0.343 |
| Number of treated CTO vessels, % | |||
| 1 | 308 (96.25) | 144 (93.51) | 0.242 |
| 2 | 12 (3.75) | 9 (5.84) | 0.342 |
| 3 | 0 | 1 (0.65) | 0.325 |
| Number of stents | 2.42±1.16 | 2.40±1.15 | 0.842 |
| Total stent length, mm | 61.13±34.18 | 61.36±36.55 | 0.948 |
Abbreviations: CTO, chronic total occlusion; LM, left main; LAD, left anterior descending; RCA, right coronary artery; LCX, left circumflex.
Table 2. Angiographic and procedural characteristics
Clinical outcomes on follow-up
After 12 months’ follow-up, the incidence of MACE was 12.19% in Clopidogrel group and 11.04% in Ticagrelor group (P>0.05), the individual components in the two groups were not significantly different either. The total bleeding rate (9.38% vs. 13.64%) and BARC 1 bleeding (8.13% vs. 12.99%) of Clopidogrel group were lower than those of Ticagrelor group, but with no statistical significance (P＞0.05) (Table 3).
| Variable | Clopidogrel (n=320) | Ticagrelor (n=154) | P value |
|---|---|---|---|
| MACE, % | 39 (12.19) | 17 (11.04) | 0.763 |
| All-cause death, % | 35 (10.94) | 17 (11.04) | 1.000 |
| Nonfatal myocardial infarction, % | 1 (0.31) | 2 (1.30) | 0.248 |
| Clinically driven revascularization, % | 3 (0.94) | 0 | 0.554 |
| Bleeding, % | 30 (9.38) | 21 (13.64) | 0.205 |
| BARC 1, % | 26 (8.13) | 20 (12.99) | 0.100 |
| BARC 2, % | 2 (0.63) | 0 | 1.000 |
| BARC 3, % | 0 | 0 | |
| BARC 5, % | 2 (0.63) | 1 (0.65) | 1.000 |
Table 3: Efficacy and safety points
Considering that the factors that might be related to bleeding were not balanced, the IPTW model was used to balance the clinical characteristics from the two groups (Figure 2).
The characteristics were significantly balanced after matching, and it was found that compared with Clopidogrel, Ticagrelor had an adverse impact on the reduction of the incidence of bleeding with the IPTW model (IPTW-OR: 1.81, 95% CI: 1.18-2.76, P=0.006) (Figure 3).
PCI has been applied to CTO at high success rates [14], but CTO-PCI patients presented with higher ischemic incidence because of more complex lesions. Therefore, prolonged DAPT duration is usually recommended for these patients [2,5]. Elderly CTO-PCI patients are also exposed to high risks of bleeding [15], which makes it vitally important to balance both thrombose and hemorrhage for CTO-PCI patients to ensure a desirable prognosis. Previous studies indicated that clinical improvement showed up, regardless whether the DAPT duration was >12 months or not after PCI in CTO patients [16,17]. Considering the reasons above, the duration of DAPT in this study was determined as 12 months. DAPT, which comprises aspirin and a P2Y12 inhibitor, reduces coronary ischemic events after PCI by preventing both stent thrombosis and non-culprit segments thrombosis via antiplatelet aggregation. As P2Y12 inhibitors recommended by many guidelines, Ticagrelor and Clopidogrel can prevent adenosine diphosphate (ADP) dependent activation of platelet aggregation by binding to the P2Y12 receptor [5, 6].
According to the results of the PLATO trial, compared with Clopidogrel, Ticagrelor showed a lower incidence of endpoint events including cardiovascular death, MI and stroke (9.8% vs. 11.7%, P<0>P=0.43) [18,19].In the ESTATE study that enrolled Taiwan acute coronary syndrome (ACS) patients, the patients who took Ticagrelor had a lower incidence of MI, stroke, or vascular death endpoints with marginal statistical significance (7.1% vs. 11.6%, P=0.07), than those taking Clopidogrel, and the incidence of all bleeding was similar (19.6% vs. 14.3%, P=0.13) [20]. Among these studies, more than 80% patients received invasive therapies (PCI or coronary artery bypass grafting (CABG)). The PLATO trial contained 587 Chinese patients (3.1%) and also 2878 elderly patients (15.45%) [18,19], and the ESTATE study included 269 (28.99%) Chinese patients older than 75 years [20]. In these studies, data concerning CTO patients was absent, and Chinese elderly patients accounted only for a small number of the subjects enrolled. Consequently, these studies could hardly represent Chinese elderly CTO population.
In the present study, all the patients were aged ≥75 years and underwent PCI with DES. After 12-month DAPT, the incidence of MACE in Ticagrelor group was lower than that in Clopidogrel group (11.04% vs. 12.19%), but the incidences of overall bleeding (13.64% vs. 9.38%) and BARC 1 bleeding (12.99% vs. 8.13%) were higher in Ticagrelor group, with no statistical significance for all the differences. After balancing clinical characteristics of the two groups, the difference of bleeding incidence was found to be statistically significant. This indicates that Ticagrelor has similar effect in reducing MACE but higher bleeding risk for Chinese elderly CTO-PCI patients. Thus, Ticagrelor showed similar effectiveness but worse safety in comparison with Clopidogrel in our study.
Clopidogrel was reported to have similar MACE but higher bleeding incidence than Ticagrelor for patients after PCI [21-23]. An “East Asian paradox” was known for pointing out that East Asian patients have lower ischemic but higher bleeding risk after PCI [24]. In the PHILO trial which targeted mostly Japanese patients, compared with Clopidogrel, Ticagrelor was found associated with higher incidence of overall bleeding events (23.8% vs. 14.7%, hazard ratio (HR): 1.72; 95% CI: 1.23-2.40) and minor bleeding events (15.2% vs. 9.2%, HR: 1.75; 95% CI: 1.15-2.67), and the incidence of ischemic events (the composite of MI, stroke or vascular-cause death) is not significantly different (9.0% vs. 6.3%, HR: 1.47; 95% CI: 0.88-2.44) [25]. The TICAKOREA trial indicated that Ticagrelor group had higher incidence of clinically significant bleeding (11.7% vs. 5.3%, P=0.002) and minor bleeding (5.2% vs. 1.3%, P=0.02) than the Clopidogrel group, and the incidence of cardiovascular death, MI and stroke was not significantly different between the two groups (9.2% vs. 5.8%, P=0.07) [26]. The Kamir-NIH study based on East Asian population showed that Ticagrelor reduced the risk of ischemic event with statistical significance (8.6% vs. 11.9%, P=0.018), but it had a significantly higher bleeding risk than Clopidogrel (10.8% vs. 4.8%, P<0>
Some study had data concerning DATP of CTO-PCI patients, however, no subjects ofDATP of CTO-PCI patients who aged ≥75 years was reported. In the GF-APT registry, stable coronary artery disease patients who undergoing complex PCI got higher risk of MACEs (11.2% vs. 8.6%) and similar risk of major bleeding (0.6% vs. 0.9%) after 12-months use of Clopidogrel compared with Ticagrelor, and Ticagrelor had higher minor bleeding risk (1.2% vs. 3.4%), 34.1% of the patients in the study were CTOs [28]. This supports our result that Ticagrelor medication has a higher incidence of minor bleeding. One research into Chinese CTO patients who underwent PCI compared the incidences of overall MACE, major bleeding and minor bleeding in normal Ticagrelor dose group and Clopidogrel group, which were (7.3% vs. 14.2%), (4.1% vs. 0.6%) and (23.4% vs. 11.9%), respectively [8]. This indicates that normal dose Ticagrelor triggered lower incidence of MACE but higher bleeding incidence compared with Clopidogrel for Chinese CTO patients. According to the POPular AGE study involving 1002 patients aged ≥70 years with non-ST-elevation acute coronary syndrome (NSTE-ACS), the primary bleeding incidence was higher in Ticagrelor group (24% vs. 18%, P=0.02), and no significant differences was detected in the incidence of cardiovascular death, MI, and stroke between the two groups (11% vs. 12%, P=0.71) [29], which are align with the conclusion that Clopidogrel tend to induce high bleeding risks in elderly NSTE-ACS patients. The MACE incidence in the POPular AGE study largely coincided with that in our study, whereas the MACE incidence of Ticagrelor group in other studies is lower than that in our study. This might be attributed to the greater complexity of lesions of elderly CTO patients, which leads to higher MACE risks. The bleeding incidence in Ticagrelor group in our study is higher than those in the TICAKOREA trial, Kamir-NIH study and GF-APT registry but is lower than incidences in other studies. This may be partly due to the research bias brought by small sample size as well as the differences of baseline and procedure characteristics between the groups that might affect the comparison of the endpoints.
Taken together, DAPT after PCI can benefit aged CTO-PCI patients, and Ticagrelor showed similar MACE but higher incidence of bleeding, especially minor bleeding (BARC 1 bleeding) in contrast to Clopidogrel. As the bleeding events were not clinically relevant, Clopidogrel and Ticagrelor are considered with similar effectiveness and safety in elderly Chinese CTO-PCI patients. However, Ticagrelor should be prescribed cautiously to patients with a high bleeding risk. This study shed lights in potential clinical application of Clopidogrel and Ticagrelor. Still, a further prospective, multi-center and large-scale trials are required to verify the effectiveness and safety of Ticagrelor and Clopidogrel in elderly CTO patients who underwent PCI.
The study still maintains a few limitations. As a single center retrospective study but with a small sample size, the selection bias was hardly avoidable and the methodological biases exist. Additionally, cardiovascular death was not identified and separately analyzed in our follow-up, with the CTO score, opening techniques or the occurrence of stroke, not considered. More, analysis of effectiveness end points wasn’t adjusted accordingly, given the unavailability of nonfatal MI date and clinically driven revascularization. Lastly, therapeutic agents such as β-blocker were not included in this study, and neither did we evaluate the major adverse effects of P2Y12 inhibitors including dyspnea, hyperuricemia, and asymptomatic heart block.
This clinical study demonstrated that Clopidogrel and Ticagrelor have similar effectiveness and safety to elderly Chinese CTO-PCI patients in improving their prognosis, yet Ticagrelor should be prescribed with caution to eliminate potential bleeding.
DAPT: dual antiplatelet therapy; PCI: percutaneous coronary intervention; CTO: chronic total occlusion; MACE: major adverse cardiac event; MI: myocardial infarction; BARC: Bleeding Academic Research Consortium; IPTW: inverse probability of treatment weighting; CAD: coronary artery disease; MI: myocardial infarction; DES: drug-eluting stents; TIMI: Thrombolysis In Myocardial Infarction; LM: left main artery；LAD: left anterior descending artery; LCX: left circumflex artery; RCA: right coronary artery; BARC: Bleeding Academic Research Consortium; DBP: diastolic blood pressure; Glu: glucose; TG: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholestero; SMD: standardized mean differences; IPTW: inverse probability of treatment weighting; ADP: adenosine diphosphate; ACS: acute coronary syndrome; CABG: coronary artery bypass grafting; HR: hazard ratio; AMI: acute myocardial infarction; MVD: multivessel disease; NSTE-ACS: non-ST-elevation acute coronary syndrome.
Declarations
The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Air Force Medical University (KY20172019-1). Written informed consents were obtained from all participants.
Consent for Publication
The consent was obtained from all authors for publication of this study.
Availability of Data and Materials
The datasets generated and analyzed in the current study are available from the corresponding author on reasonable request.
Funding
This work was supported by Shaanxi Province Key Research and Development Program General Project—Social Development (2018SF-153), Xi’an Science and Technology Project (20YXYJ0003(4)), New Clinical Technology and New Business of Xijing Hospital (XJGX15Y39), Bethune-Merck Diabetes Research Foundation (G2017044).
Conflict of Interest
The authors have no conflicts of interest to declare.
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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
My Testimonial Covering as fellowing: Lin-Show Chin. 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.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
