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BackgroundThis study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI).MethodsElectronic databases were searched for studies comparing pretreatment with different types and doses of P2Y12 inhibitors or comparison between P2Y12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event.ResultsA total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included—nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment (RR = 0.78, 95% CI:0.66, 0.91, P 0.05).ConclusionsIn patients with NSTE-ACS, pretreatment with P2Y12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y12 inhibitors can be considered for the selection of pretreatment drugs.

AimsTo explore the effects of age and sex on the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with the three-vessel disease (TVD).Methods and ResultsThe study is a subanalysis of data from a prospective cohort of 8,943 patients with angiographically confirmed TVD at Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China. The primary end point was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. In total, 2,819 patients with NSTE-ACS who received CABG (43.6%) or PCI (56.4%) were included, among whom 32.7% were of 65–74 years, 7.2% were ≥75 years, and 22.6% were women. The median follow-up duration was 6.8 years. The superiority of CABG relative to PCI in terms of MACCE was decreased with age (adjusted hazard ratio [HR] [95% confidence interval (CI)]:

IntroductionThe Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism.Methods/DesignThe study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial.DiscussionThe purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism.Trial RegistrationChina Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020.

AimsWhether early or delayed dual antiplatelet therapy initiation is better in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is unclear. We assessed the evidence for comparing the efficacy and safety of early vs. delayed P2Y12 inhibitor initiation in NSTE-ACS.MethodsThe randomized controlled trials with available comparisons between early and delayed initiation of P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with NSTE-ACS until January 2021 were reviewed. The primary outcomes were trial-defined major adverse cardiovascular events (MACEs) and bleeding. Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, urgent coronary revascularization, and stroke. Frequentist random-effects network meta-analyses were conducted, ranking best treatments per outcome with p-scores.ResultsA total of nine trials with intervention arms including early and delayed initiation of clopidogrel (n = 5), prasugrel (n = 8), or ticagrelor (n = 6) involving 40,096 patients were included. Early prasugrel (hazard ratio [HR], 0.59; 95% confidence interval [95%CI], 0.40–0.87), delayed prasugrel (HR, 0.60; 95%CI 0.43–0.84), and early ticagrelor (HR, 0.84; 95%CI, 0.74–0.96) significantly reduced MACE compared with early clopidogrel, but increased bleeding risk. Delayed prasugrel ranked as the best treatment to reduce MACE (p-score=0.80), early prasugrel to reduce all-cause mortality, cardiovascular mortality, stent thrombosis, and stroke, and delayed clopidogrel to reduce bleeding (p-score = 0.84). The risk of bias was low for all trials.ConclusionIn patients with NSTE-ACS, delayed prasugrel initiation was the most effective strategy to reduce MACE. Although early prasugrel was the best option to reduce most secondary cardiovascular outcomes, it was associated with the highest bleeding risk. The opposite was found for delayed clopidogrel.

Background: Visceral adiposity index (VAI), a surrogate marker of adiposity and insulin resistance, has been demonstrated to be significantly related to cardiovascular disease. It remains indistinct whether VAI predicts adverse prognosis after percutaneous coronary intervention (PCI) for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and type 2 diabetes mellitus (T2DM).Methods: A total of 798 participants who met the enrollment criteria were finally brought into this study. VAI was determined by waist circumference, body mass index, fasting triglyceride, and high-density lipoprotein cholesterol as previously reported. Adverse prognosis included all-cause death, non-fatal myocardial infarction, non-fatal ischemic stroke, and ischemia-driven revascularization, the composite of which was defined as the primary endpoint.Results: Higher VAI maintained as a significant and independent risk predictor for the primary endpoint, regardless of the adjustment for the various multivariate models [hazard ratio (95% CI) for fully adjusted model: 2.72 (2.02–3.68), p < 0.001]. The predictive value of VAI was further confirmed in sensitivity analysis where VAI was taken as a continuous variate. There was a dose-response relationship of VAI with the risk of the primary endpoint (p for overall association < 0.001). Moreover, the ability of VAI on the prediction of the primary endpoint was consistent between subgroups stratified by potential confounding factors (all p for interaction > 0.05). VAI exhibited a significant incremental effect on risk stratification for the primary endpoint beyond existing risk scores, expressed as increased Harrell's C-index, significant continuous net reclassification improvement, and significant integrated discrimination improvement.Conclusion: VAI is a significant indicator for predicting worse prognosis and plays an important role in risk stratification among patients with NSTE-ACS and T2DM undergoing elective PCI. The present findings require further large-scale, prospective studies to confirm.

Background: This study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y 12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI)., Methods: Electronic databases were searched for studies comparing pretreatment with different types and doses of P2Y 12 inhibitors or comparison between P2Y 12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y 12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event., Results: A total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included-nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y 12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y 12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment ( RR  = 0.78, 95% CI :0.66, 0.91, P  < 0.05) and double-loading pretreatment ( RR  = 0.62, 95% CI :0.41, 0.95, P  < 0.05) had a lower incidence of MACCEs. There was no statistically significant difference in the incidence of major bleeding events among the six pretreatments ( P  > 0.05)., Conclusions: In patients with NSTE-ACS, pretreatment with P2Y 12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y 12 inhibitors can be considered for the selection of pretreatment drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Li, Lei, Zhao, Yang, An, Wang, Sun, Li and Xue.)

Introduction: The Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism., Methods/design: The study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial., Discussion: The purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism., Trial Registration: China Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Guo, Shi, Shi, Deng, Wang, Wang, Wang and Chen.)

Aims: To explore the effects of age and sex on the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with the three-vessel disease (TVD)., Methods and Results: The study is a subanalysis of data from a prospective cohort of 8,943 patients with angiographically confirmed TVD at Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China. The primary end point was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. In total, 2,819 patients with NSTE-ACS who received CABG (43.6%) or PCI (56.4%) were included, among whom 32.7% were of 65-74 years, 7.2% were ≥75 years, and 22.6% were women. The median follow-up duration was 6.8 years. The superiority of CABG relative to PCI in terms of MACCE was decreased with age (adjusted hazard ratio [HR] [95% confidence interval (CI)]: <65 years: 0.662 [0.495-0.885], p = 0.005; 65-74 years: 0.700 [0.512-0.956], p = 0.025; ≥75 years: 0.884 [0.529-1.479], p = 0.640) and was only seen in men (adjusted HR [95% CI]: men: 0.668 [0.526-0.848], p = 0.001; women: 0.713 [0.505-1.006], p = 0.054). Significant treatment-by-sex and treatment-by-age interactions were observed in patients ≥ 75 years and women, respectively, ( p interaction with sex = 0.001; p interaction with age = 0.002)., Conclusion: Coronary artery bypass grafting is favorable for most NSTE-ACS patients with TVD. The preponderance of CABG over PCI disappeared in patients ≥ 75 years and women. PCI is superior in women ≥ 75 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiang, Xu, Tian, Zhao, Feng, Wang, Zhang, Sun, Xu, Liu, Xu, Zhao, Hui, Gao, Song and Yuan.)

Background: Visceral adiposity index (VAI), a surrogate marker of adiposity and insulin resistance, has been demonstrated to be significantly related to cardiovascular disease. It remains indistinct whether VAI predicts adverse prognosis after percutaneous coronary intervention (PCI) for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and type 2 diabetes mellitus (T2DM). Methods: A total of 798 participants who met the enrollment criteria were finally brought into this study. VAI was determined by waist circumference, body mass index, fasting triglyceride, and high-density lipoprotein cholesterol as previously reported. Adverse prognosis included all-cause death, non-fatal myocardial infarction, non-fatal ischemic stroke, and ischemia-driven revascularization, the composite of which was defined as the primary endpoint. Results: Higher VAI maintained as a significant and independent risk predictor for the primary endpoint, regardless of the adjustment for the various multivariate models [hazard ratio (95% CI) for fully adjusted model: 2.72 (2.02-3.68), p < 0.001]. The predictive value of VAI was further confirmed in sensitivity analysis where VAI was taken as a continuous variate. There was a dose-response relationship of VAI with the risk of the primary endpoint ( p for overall association < 0.001). Moreover, the ability of VAI on the prediction of the primary endpoint was consistent between subgroups stratified by potential confounding factors (all p for interaction > 0.05). VAI exhibited a significant incremental effect on risk stratification for the primary endpoint beyond existing risk scores, expressed as increased Harrell's C-index, significant continuous net reclassification improvement, and significant integrated discrimination improvement. Conclusion: VAI is a significant indicator for predicting worse prognosis and plays an important role in risk stratification among patients with NSTE-ACS and T2DM undergoing elective PCI. The present findings require further large-scale, prospective studies to confirm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Cheng, Xu, Zhao, Liu, Sun and Zhou.)