Post-marketing effectiveness evaluation of traditional Chinese medicine in paradigm based on "proving efficacy, conforming standard, and exploring mechanism":a case study of Danhong Injection / 中国中药杂志

At present, new concepts, new technologies, and new methods are emerging in the field of medical research, breaking through the inherent thinking patterns and research models, and promoting the transformation of the research paradigm of traditional Chinese medicine(TCM). This paper gave a case study of clinical research in Danhong Injection in the treatment of chronic stable angina, and based on the background of the study, index evaluation model, experimental design method, blind implementation of placebo, data management system, and exploration of clinical efficacy mechanism of traditional Chinese medicine compounds under the framework of modular pharmacology, the scientific idea of "proving efficacy, conforming standard, and exploring mechanism" was used as the guideline to discuss the research model of reevaluation of the effectiveness of post-marketing TCM varieties. This paper drew a target network map of Danhong Injection in the treatment of chronic stable angina for the first time, which was composed of targeted functional modules. By combining evidence-based clinical research with modular pharmacology framework, changes in the pharmacolo-gical mechanism were finally associated with changes in clinical efficacy, and the advantages of phenotypic correlation of efficacy were explored. This study is expected to provide references for the post-marketing effectiveness evaluation and new ideas for the phenotypic pharmacological mechanism study of multi-target TCM compounds and precise treatment, thereby promoting the innovative development of TCM.

Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

Associação entre os Níveis Séricos de Elabela e Oclusão Total Crônica em Pacientes com Angina Pectoris Estável / Association Between Serum Elabela Levels and Chronic Totally Occlusion in Patients with Stable Angina Pectoris

Resumo Fundamento: Os efeitos benéficos do elabela no sistema cardiovascular foram demonstrados em estudos. Objetivo: Comparar os níveis séricos de elabela de pacientes com oclusão total crônica (OTC) com pacientes controle com artérias coronárias normais e investigar se há correlação com o desenvolvimento colateral. Métodos: Estudo transversal e prospectivo. O estudo incluiu cinquenta pacientes (28,0% mulheres, idade média 61,6±7,3 anos) com OTC em pelo menos um vaso coronário e 50 pacientes (38% mulheres, idade média 60,7±6,38 anos) com artérias coronárias normais. Os pacientes do grupo OTC foram divididos em dois grupos: Rentrop 0-1, composto por pacientes com fraco desenvolvimento colateral e Rentrop 2-3, composto por pacientes com bom desenvolvimento colateral. Além da idade, sexo, características demográficas e exames laboratoriais de rotina dos pacientes, foram medidos os níveis de elabela. Resultados: As características demográficas e os valores laboratoriais mostraram-se semelhantes em ambos os grupos. Ao passo que o nível médio de NT-proBNP e troponina estava maior no grupo OTC, o nível médio de elabela estava menor (p<0,05 para todos). Na análise de regressão multivariada, os níveis de NT-proBNP e elabela foram considerados preditores independentes para OTC. Além disso, o nível de elabela apresentou-se estatisticamente maior em pacientes do grupo Rentrop 2-3 em comparação com os pacientes do grupo Rentrop 0-1 (p<0,05). Conclusões: Em nosso estudo, mostramos que o nível médio de elabela estava baixo em pacientes com OTC em comparação com pacientes normais. Além disso, constatamos que o nível de elabela é inferior em pacientes com desenvolvimento colateral fraco em comparação com pacientes com bom desenvolvimento colateral. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background: The beneficial effects of Elabela on the cardiovascular system have been shown in studies. Objective: To compare serum Elabela levels of chronic total occlusion (CTO) patients with control patients with normal coronary arteries, and to investigate whether there is a correlation with collateral development. Methods: The study was planned cross-sectionally and prospectively. Fifty patients (28.0% female, mean age 61.6±7.3years) with CTO in at least one coronary vessel and 50 patients (38% female, mean age 60,7±6.38 years) with normal coronary arteries were included in the study. Patients in the CTO group were divided into two groups as Rentrop 0-1, those with weak collateral development, and Rentrop 2-3 with good collateral development. In addition to the age, sex, demographic characteristics and routine laboratory tests of the patients, Elabela levels were measured. Results: Demographic characteristics and laboratory values were similar in both groups. While the mean NT-proBNP and troponin were higher in the CTO group, the Elabela mean was lower (p <0.05 for all). In the multivariate regression analysis, NT-proBNP and Elabela levels were found to be independent predictors for CTO. Also, Elabela level was found to be statistically higher in Rentrop class 2-3 patients compared to Rentrop class 0-1 patients (p<0.05). Conclusion: In our study, we showed that the average Elabela level was low in CTO patients compared to normal patients. In addition, we found the level of Elabela to be lower in patients with weak collateral development compared to patients with good collateral development. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Effectiveness and Safety of Acupoint Application of Guan Xin Su He Pill () for Patients with Chronic Stable Angina Pectoris: A Multi-Center, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To assess the clinical effectiveness of acupoint application (AP) of Guan Xin Su He Pill (, GXSHP) for patients with chronic stable angina pectoris (CSAP).@*METHODS@#This study was carried out in 3 local hospitals in Chengdu, China. After baseline evaluation, eligible patients were randomly assigned to the placebo application for acupoints (PAA) group or the herbal application for acupoints (HAA) group. Patients in the HAA group underwent AP with herbal powder, which was mainly GXSHP, and patients in the PAA group underwent AP with sham drugs. For each treatment session, unilateral acupoints including Neiguan (PC 6), Danzhong (RN 17), Xinshu (BL 15) and Jueyinshu (BL 14), were stimulated for both groups. AP was performed 3 times a week with a 2-day interval for 4 weeks. The primary outcome was the frequency of angina pectoris attacks per week, while the secondary outcomes included angina pain intensity measured by the Visual Analogue Scale (VAS), dose of rescue oral drugs (nitroglycerin), scores on the Seattle Angina Questionnaire (SAQ), Self-Rating Anxiety Scale scores (SAS) and Self-Rating Depression Scale scores (SDS). Clinical outcomes were measured at week 0, 4 and 8. The safety of AP of GXSHP treatment for CSAP were assessed.@*RESULTS@#A total of 121 patients were enrolled. Baseline characteristics were comparable across the 2 groups. After treatment, the angina attack numbers in the HAA group were significantly reduced from 11.00 to 4.81 (P<0.05). While, for PAA group, the angina frequency was not significantly improved (baseline 10.55; post-treatment 11.05). The HAA group had significantly fewer angina attacks than the PAA group (P<0.05). Pain intensity measured by VAS in HAA group was significantly reduced from 4.06 to 3.02 (P<0.05). While, for PAA group, the VAS was significantly increased (baseline 3.62; post-treatment 3.96; P<0.05). Clinical outcomes showed better improvement after treatment in the HAA group than in the PAA group in terms of oral administration of rescue drugs, SAS, SDS and SAQ scores (P<0.05). The adverse events were also reported.@*CONCLUSION@#AP of GXSHP is a safe and effective treatment for CSAP patients (Registration No. NCT02029118).

Estudio de la deformación miocárdica longitudinal en pacientes con cardiopatía isquémica / Study of longitudinal myocardial deformation in patients with ischemic cardiopathy

Resumen Introducción: Las enfermedades cardiovasculares constituyen la primera causa de muerte en Cuba y la mayoría de los países desarrollados. La ecocardiografía con speckle tracking bidimensional (ST 2D) es una técnica reciente en la evaluación de la función cardíaca. Objetivos: Determinar la relación entre la deformación miocárdica medida por ST 2D y el estado de la circulación coronaria en pacientes con cardiopatía isquémica, en el CIMEQ, durante un año. Material y método: Se realizó un estudio analítico y transversal con 55 pacientes con indicación de coronariografía sometidos a ecocardiograma bidimensional y estudio de ST 2D con medición de la deformación longitudinal (DLG). Se crearon dos grupos: enfermedad coronaria significativa (ECS = 32) y no significativa (ECNS = 23). Se utilizó SSPS para análisis de los resultados. Resultados: La edad promedio fue mayor en la ECS (55.6 ± 9.3 vs. 61.8 ± 8.8; p = 0.014). Predominaron los hombres con ECS (47.3%), los hipertensos (ECS = 90.6% y ENCS = 65.2%; p = 0.02) y los fumadores (ECS = 59.4% y ENCS = 17.4%; p = 0.002). El diagnóstico más frecuente fue la angina crónica estable (87%). En la ECS predominó la enfermedad de tres vasos (75%). La DLG fue menor en la ECS [(-20.0 ± 3.2 vs. -22.1 ± 3.6; p = 0.035); AUC = 0.458]. No hubo diferencias en la DLG según el número de vasos significativamente afectados. Conclusiones: Los resultados encontrados no justifican el empleo del ST 2D para diferenciar la ECS.

Abstract Introduction: Cardiovascular diseases are the leading cause of death in Cuba and most of the developed countries. Two-dimensional speckle tracking echocardiography (2D ST) is a recent technique in the evaluation of cardiac function. Objectives: To determine the relationship between myocardial deformation measured by 2D ST and coronary circulation in patients with ischemic heart disease, in the CIMEQ, for 1 year. Material and method: An analytical, cross-sectional study was carried out with 55 patients with an indication for coronary angiography who underwent 2D echocardiography and 2D ST study with longitudinal strain measurement (LSM). Two groups significant coronary disease (SCD = 32) and not significant (NSCD = 23) were created. SSPS was used to analyze the results. Results: The average age was higher in SCD (55.6 ± 9.3 vs. 61.8 ± 8.8, p = 0.014). Men with SCD (47.3%), hypertensive (SCD = 90.6% and NSCD = 65.2%, p = 0.02) and smokers (SCD = 59.4% and NSCD = 17.4%, p = 0.002) predominated. The most frequent diagnosis was chronic stable angina (87%). Three-vessel disease (75%) prevailed in SCD. The LMS was lower in SCD ([−20.0 ± 3.2 vs. −22.1 ± 3.6, p = 0.035]; AUC = 0.458). There were no differences in LSM according to the number of significantly diseased vessels. Conclusions: The results found do not justify the use of 2D ST to discriminate SCD.

SYNTAX Score and SYNTAX Score II Can Predict the Clinical Outcomes of Patients with Left Main and/or 3-Vessel Disease Undergoing Percutaneous Coronary Intervention in the Contemporary Cobalt-Chromium Everolimus-Eluting Stent Era

BACKGROUND AND OBJECTIVES: The impact of SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SS) and SS II in patients who receive percutaneous coronary intervention with second-generation everolimus-eluting stents (EES) has not been fully validated.METHODS: The SS, SS II were calculated in 1,248 patients with left main and/or 3-vessel disease treated with EES. Patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), any revascularization) and target lesion failure (TLF: cardiac death, target-vessel MI, target lesion revascularization) were analyzed.RESULTS: The mean SS was 21.1±9.6. Three-year POCE increased according to the SS group (15.2% vs. 19.9% vs. 27.4% for low (≤22), intermediate (≥23, ≤32), high (≥33) SS groups, p<0.001). By multivariate Cox proportional hazard analysis, SS group was an independent predictor of 3-year POCE (hazard ratio, 1.324; 95% confidence interval, 1.095–1.601; p=0.004). The receiver operating characteristic curves revealed that the SS II was superior to the SS for 3-year POCE prediction (area under the curve [AUC]: 0.611 vs. 0.669 for SS vs. SS II, p=0.019), but not for 3-year TLF (AUC: 0.631 vs. 0.660 for SS vs. SS II, p=0.996). In subgroup analysis, SS II was superior to SS in patients with cardiovascular clinical risk factors, and in those presenting as stable angina.CONCLUSIONS: The usefulness of SS and SS II was still valid in patients with left main and/or 3-vessel disease. SS II was superior to SS for the prediction of patient-oriented outcomes, but not for lesion-oriented outcomes.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00698607ClinicalTrials.gov Identifier: NCT01605721

Comparison of Exercise Performance and Clinical Outcome Between Functional Complete and Incomplete Revascularization

BACKGROUND AND OBJECTIVES: Although percutaneous coronary intervention (PCI) is recommended to improve symptoms in patients with stable ischemic heart disease (SIHD), improvement of exercise performance is controversial. This study aimed to investigate changes in exercise duration after PCI according to functional completeness of revascularization by comparing pre- and post-PCI exercise stress test (EST).METHODS: Patients with SIHD were enrolled from a prospective PCI registry, and divided into 2 groups: 1) functional complete revascularization (CR) group had a positive EST before PCI and negative EST after PCI, 2) functional incomplete revascularization (IR) group had positive EST before and after PCI. Primary outcome was change in exercise duration after PCI and secondary outcome was major adverse cardiac events (MACE, a composite of any death, any myocardial infarction, and any ischemia-driven revascularization) at 3 years after PCI.RESULTS: A total of 256 patients (149 for CR group, and 107 for IR group) were eligible for analysis. Before PCI, exercise duration was not significantly different between the functional CR and IR groups (median 540 [interquartile range; IQR, 414, 602] vs. 480 [402, 589] seconds, p=0.091). After PCI, however, the CR group had a significantly higher increment of exercise duration than the IR group (median 62.0 [IQR, 12.0, 141.0] vs. 30.0 [−11.0, 103.5] seconds, p=0.011). The functional CR group also had a significantly lower risk of 3-year MACE (6.2% vs. 26.1%; adjusted hazard ratio, 0.19; 95% confidence interval, 0.09–0.41; p<0.001).CONCLUSIONS: Functional CR showed a higher increment of exercise duration than functional IR.

Long-Term Outcomes in Patients Undergoing Percutaneous Coronary Intervention with or without Preprocedural Exercise Stress Test

Clinical Outcomes and Cost-Effectiveness Analysis of FFR Compared with Angiography in Multivessel Disease Patient / Impacto Clínico e Custo-Efetividade da FFR em Comparação à Angiografia em Pacientes com Doenças Multiarteriais Submetidos à ICP

Abstract Background: In multivessel disease patients with moderate stenosis, fractional flow reserve (FFR) allows the analysis of the lesions and guides treatment, and could contribute to the cost-effectiveness (CE) of non-pharmacological stents (NPS). Objectives: To evaluate CE and clinical impact of FFR-guided versus angiography-guided angioplasty (ANGIO) in multivessel patients using NPS. Methods: Multivessel disease patients were prospectively randomized to FFR or ANGIO groups during a 5 year-period and followed for < 12 months. Outcomes measures were major adverse cardiac events (MACE), restenosis and CE. Results: We studied 69 patients, 47 (68.1%) men, aged 62.0 ± 9.0 years, 34 (49.2%) in FFR group and 53 (50.7%) in ANGIO group, with stable angina or acute coronary syndrome. In FFR, there were 26 patients with biarterial disease (76.5%) and 8 (23.5%) with triarterial disease, and in ANGIO, 24 (68.6%) with biarterial and 11 (31.4%) with triarterial disease. Twelve MACEs were observed - 3 deaths: 2 (5.8%) in FFR and 1 (2.8%) in ANGIO, 9 (13.0%) angina: 4(11.7%) in FFR and 5(14.2%) in ANGIO, 6 restenosis: 2(5.8%) in FFR and 4 (11.4%) in ANGIO. Angiography detected 87(53.0%) lesions in FFR, 39(23.7%) with PCI and 48(29.3%) with medical treatment; and 77 (47.0%) lesions in ANGIO, all treated with angioplasty. Thirty-nine (33.3%) stents were registered in FFR (0.45 ± 0.50 stents/lesion) and 78 (1.05 ± 0.22 stents/lesion) in ANGIO (p = 0.0001), 51.4% greater in ANGIO than FFR. CE analysis revealed a cost of BRL 5,045.97 BRL 5,430.60 in ANGIO and FFR, respectively. The difference of effectiveness was of 1.82%. Conclusion: FFR reduced the number of lesions treated and stents, and the need for target-lesion revascularization, with a CE comparable with that of angiography.

Resumo Fundamentos: Em pacientes multiarteriais e lesões moderadas, a reserva de fluxo fracionada (FFR) avalia cada lesão e direciona o tratamento, podendo ser útil no custo-efetividade (CE) de implante de stents não farmacológicos (SNF). Objetivos: Avaliar CE e impacto clínico da angioplastia + FFR versus angioplastia + angiografia (ANGIO), em multiarteriais, utilizando SNF. Métodos: pacientes com doença multiarteriais foram randomizados prospectivamente durante ±5 anos para FFR ou ANGIO, e acompanhados por até 12 meses. Foram avaliados eventos cardíacos maiores (ECAM), reestenose e CE. Resultados: foram incluídos 69 pacientes, 47(68,1%) homens, 34(49,2%) no FFR e 35(50,7%) no ANGIO, idade 62,0 ± 9,0 anos, com angina estável e Síndrome Coronariana Aguda estabilizada. No FFR, havia 26 com doença (76,5%) biarterial e 8 (23,5%) triarterial, e no grupo ANGIO, 24(68,6%) biarteriais e 11(31,4%) triarteriais. Ocorreram 12(17,3%) ECAM - 3(4,3%) óbitos: 2(5,8%) no FFR e 1(2,8%) no ANGIO, 9(13,0%) anginas, 4(11,7%) no FFR e 5(14,2%) no ANGIO, 6 reestenoses: 2(5,8%) no FFR e 4 (11,4%) no ANGIO. Angiografia detectou 87(53,0%) lesões no FFR, 39(23,7%) com ICP e 48(29,3%) com tratamento clínico; e 77(47,0%) lesões no ANGIO, todas submetidas à angioplastia. Quanto aos stents, registrou-se 39(33,3%) (0,45 ± 0,50 stents/lesão) no FFR e 78(66,6%) (1,05 ± 0,22 stents/lesão) no ANGIO (p = 0,0001); ANGIO utilizou 51,4% a mais que o FFR. Análise de CE revelou um custo de R$5045,97 e R$5.430,60 nos grupos ANGIO e FFR, respectivamente. A diferença de efetividade foi 1,82%. Conclusões: FFR diminuiu o número de lesões tratadas e de stents e necessidade de revascularização do vaso-alvo, com CE comparável ao da angiografia.

Shensong Yangxin Capsules in the adjuvant treatment of stable angina pectoris:a Meta-analysis and trial sequential analysis / 中国中药杂志

To systemically evaluate the benefits and side effects of Shensong Yangxin Capsules( SYC) in the adjuvant treatment of stable angina pectoris( SAP). Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP,Wan Fang database) were retrieved to collect the randomized controlled trials( RCTs) about therapeutic efficacy of SYC combined with routine drug( trial group) vs routine drug( control group) in the treatment of SAP. The methodological quality of the RCTs was evaluated based on the cochrane risk of bias assessment tool. The data were extracted and Meta-analyzed by Reviewer Manager 5. 3. TSA 0. 9 software was used for trial sequential analysis( TSA) of the total effective rate of symptoms improvement. A total of 15 RCTs with 1 316 participants were included. RESULTS:: of Meta-analysis showed that the total effective rate of angina symptoms improvement( RR = 1. 15,95% CI[1. 09,1. 21],P<0. 001) of trial group were significantly higher than those of control group,with statistical significance,the total effective rate of electrocardiograms( ECG) improvement( RR = 1. 10,95% CI[0. 94,1. 29],P = 0. 25) of trial group were significantly higher than those of control group,but the difference was not statistically significant. After treatment,the improvement of the total time of 24 h general ischemia( SMD =-1. 21,95%CI[-1. 97,-0. 45],P = 0. 002),the ST-segment depression amplitude( SMD =-1. 30,95%CI [-1. 52,-1. 09],P<0. 001),the duration of angina pectoris attack( SMD =-1. 16,95% CI[-1. 36,-0. 95],P< 0. 001),the angina pectoris attack every week( SMD =-0. 80,95%CI[-1. 10,-0. 50],P<0. 001),the onsumption of nitroglycerin every week( SMD=-0. 72,95%CI[-1. 05,-0. 39],P<0. 001) in the trial group were better than that of the control group,and the difference was statistically significant. Besides,the improvement of the blood lipid and high sensitivity C reactive protein( hs-CRP) in the trial group were better than those of the control group after treatment,and the difference was statistically significant( P< 0. 001). Funnel plots and Egger's linear regression showed that there was no publication bias. By sensitivity analysis,it showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. TSA analysis showed that the evidence of Meta-analysis was reliable. SYC combined with routine Western medicine treatment for SAP can improve the total effective rate of angina pectoris,reduce 24 h total ischemia time,ST segment depression amplitude,duration of angina pectoris attack,frequency of angina pectoris attack and nitroglycerin dosage,and also can improve blood lipid and hs-CRP levels.

Trimetazidine in angina and poor muscle function: protocol for a randomized controlled study / 中华医学杂志(英文版)

BACKGROUND@#Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study.@*METHODS@#This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study.@*DISCUSSION@#This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.

Shenzhu Guanxin Recipe Granules () for Improving Exercise Tolerance in Patients with Stable Angina (SERIES Trial): A Protocol of Multicenter, Randomized, Double-Blind, Placebo Parallel Controlled Clinical Trial / 中国结合医学杂志

BACKGROUND@#Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients.@*METHODS@#A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up.@*DISCUSSION@#This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504).

On-Pump beating/non-beating cabg in stable angina have similar outcomes

Abstract Objective: On pump beating/non-beating coronary artery bypass grafts (CABG) has been compared in patients with unstable angina and/or severe left ventricular dysfunction. There is scarce evidence regarding the beneficial use of on-pump beating CABG in patients with stable angina and normal left ventricular function. Our aim was to study the postoperative results using both techniques in this group of patients. Methods: One thousand one hundred and forty-five patients with stable angina underwent on-pump isolated CABG in Uruguay from 2011 to 2015. Patients were grouped into beating/non-beating CABG. Operative mortality and long-term survival were evaluated as primary outcome. Logistic regression analysis was performed to define the predictive role of aortic cross clamp (AXC) on prolonged inotropic support, ventilator support and intraoperative glycemia. Results: Among the included patients, 988 underwent aortic cross clamp. No differences were found in operative mortality, stroke and long-term survival among both groups. Patients without AXC showed higher intraoperative values of glycemia and higher incidence of postoperative prolonged mechanical ventilator support (7.6% vs. 2.4%; P=0.001). The need for prolonged inotropic support was lower in this group of patients (27.4% vs. 49.5%; P<0.001). Conclusion: On-pump beating CABG has similar operative mortality and long-term survival compared with conventional AXC. Higher intraoperative glycemia and higher incidence for prolonged mechanical ventilator is associated with on-pump beating CABG. On the contrary, higher incidence for prolonged inotropic support is associated with AXC. Taking these factors into consideration, both techniques are safe and allow the surgeon to choose the most comfortable option.

CANG and preoperative use of beta-blockers in patients with stable angina are associated with better cardiovascular survival

Abstract Objective: In contrast to unstable angina, optimal therapy in patients with stable angina is debated. Our aim was to evaluate the outcomes of patients with stable angina scheduled for isolated coronary artery bypass grafts and the effect of preoperative use of beta-blockers. Overall and cardiovascular survivals were our primary outcome. Operative mortality and postoperative complications along with subgroup analysis of diabetic patients were our secondary outcomes. Methods: Retrospective evaluation of patients with stable angina scheduled for isolated coronary artery bypass grafts was included. Pre- and postoperative variables were extracted from the institution database. Survival was obtained from the National Registry. Results: We included 282 patients with stable angina, with a mean age of 65.6±9.5 years. 26.6% were female and 38.7% had diabetes. Three-vessel disease was present in 76.6% of patients. Previous beta-blocker treatment was evident in 69.9% of patients. 10-year overall survival in the whole population was 60.5% (95% confidence interval [CI]: 50.3-70.7%). Operative mortality during the study period was 3.5%. Patients with preoperative use of beta-blocker therapy had better overall survival (9.0 years, 95%CI: 8.6-9.5) than those without treatment (7.9 years, 95%CI: 7.1-8.8 years; P=0.048). Predictors for overall survival were: hypertension, diabetes, and age. Predictors for cardiovascular survival in diabetic patients were: beta-blocker use, gender, and age. Conclusion: Coronary artery bypass grafts surgery in patients with stable angina carries low operative mortality, postoperative complications, and excellent long-term cardiovascular survival. The preoperative use of beta-blockers in diabetic patients is associated with better cardiovascular survival after coronary artery bypass grafts.

Health-promoting Lifestyle in Patients after Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the status of health-promoting behaviors in patients after percutaneous coronary intervention (PCI) and explore what factors affect healthy lifestyle behaviors. METHODS: A total of 120 patients with coronary artery disease after PCI was included in this study. The Health Promoting Lifestyle Profile (HPLP) II was used to assess health-promoting lifestyle behavior. Data analysis was performed by t-test, analysis of variance, and multiple linear stepwise regression analyses. RESULTS: The average age of the participants was 60.10±9.84 (range, 37–81) years old. Among the participants, 86.7% were men and 13.3% were women. In all, 24.2% of the patients had an excellent level of health-promoting lifestyle and 74.2% had a moderate level of health-promoting lifestyle. The spiritual growth scores were the highest, while stress management and physical activity scores were the lowest. The level of health-promoting lifestyle was higher for people with higher income and a diagnosis of stable angina. CONCLUSIONS: Healthcare providers should focus on promoting physical exercise and stress management for patients after PCI. It is also necessary to keep an eye out for patients with low income and severe illness to encourage a health-promoting lifestyle in these subsets of patients.

Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system / 亚洲男科学杂志(英文版)

Testosterone deficiency is common in men with cardiovascular disease (CVD), and randomized placebo-controlled trials (RCTs) have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise (VO2max) and muscle strength in chronic heart failure (CHF), shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade (L-calcium channel) and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2maxand vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol (HDL-C) differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-10 (IL-10) which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events (MACEs) and mortality in studies which have treated men with testosterone deficiency. No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis.

Clinical Implications of Moderate Coronary Stenosis on Coronary Computed Tomography Angiography in Patients with Stable Angina

PURPOSE: The present study investigated the diagnostic accuracy and clinical implications of moderate stenosis (50–69%, Coronary Artery Disease Reporting and Data System, grade 3) on coronary computed tomography angiography (CCTA), compared with invasive coronary angiography (ICA). MATERIALS AND METHODS: Two hundred and seventy-six patients who underwent ICA due to moderate stenosis alone on CCTA were selected from our prospective registry cohort. RESULTS: Diagnostic concordance between CCTA and ICA was found in only 50 (18%) patients. Among the 396 vessels and 508 segments with moderate stenosis, diagnostic concordance was found in 132 vessels (33%) and 127 segments (25%). Segments with calcified plaque had lower diagnostic concordance than those with mixed or non-calcified plaque (22% vs. 28% vs. 27%, respectively, p=0.001). While calcified plaque burden did not have an influence on severe stenosis (≥70%) on ICA, higher burden of non-calcified plaque was correlated with a greater incidence of ICA-based severe stenosis, which was more frequent in patients with ≥3 segments of non-calcified plaque (75%) than those without non-calcified plaque (22%, p < 0.001). Typical angina and mixed or non-calcified plaque were correlated with a higher incidence of under-diagnosis, while the use of next-generation computed tomography scanners reduced the incidence of under-diagnosis. Increased body weight, left circumflex artery involvement, and calcified plaque were independent factors that increased the risk of over-diagnosis of CCTA. CONCLUSION: The diagnosis of moderate stenosis by CCTA may be limited in estimating the exact degree of ICA-based anatomical stenosis. Unlike calcific burden, non-calcific burden was positively correlated with the presence of severe stenosis on ICA.

Custo-efetividade de trimetazidina no tratamento de angina estável em pacientes diabéticos não respondedores a betabloqueadores, nitratos e bloqueadores do canal de cálcio / Cost-effectiveness of trimetazidine for stable angina treatment in non-responder diabetics after beta blockers, nitrates and calcium channel blockers

Objetivo: Avaliar o custo-efetividade da trimetazidina (TMZ) associada ao tratamento convencional (diurético, ácido acetilsalicílico [AAS], betabloqueador, inibidores da enzima de conversão da angiotensina (IECA), nitrato, estatina, digitálico e antagonista dos canais de cálcio) versus tratamento convencional isolado no tratamento de pacientes diabéticos com angina estável não respondedores a betabloqueadores, nitratos e bloqueadores do canal de cálcio sob a perspectiva do Sistema Público de Saúde (SUS). Métodos: Foi elaborado um modelo de Markov, com ciclos de 1 ano, que acompanhou os pacientes ao longo do curso natural da doença até o final de suas vidas. Dados clínicos foram obtidos a partir de revisão da literatura. Custos unitários foram extraídos de bases de dados oficiais. Apenas custos médicos diretos foram contemplados. Custos e benefícios foram descontados a uma taxa de 5% ao ano. Desfecho clínico foi expresso como episódio de hospitalização por angina pectoris (EHAP) evitado. Análise de sensibilidade univariada foi realizada para determinar os parâmetros de maior influência nos resultados, variando-os em mais ou menos 20% comparado ao cenário base. Resultados: O tratamento com TMZ mostrou maior benefício comparado ao tratamento convencional e gerou uma Razão de Custo-Efetividade Incremental de R$ 7.344,96 por EHAP evitado. O parâmetro de maior impacto no resultado foi o número de episódios de angina pectoris. Apesar do alto impacto, este não alterou o resultado da análise, mantendo-o custo-efetivo. Conclusão: TMZ associada ao tratamento convencional mostrou ser uma alternativa eficaz, segura e custo-efetiva para o tratamento de pacientes diabéticos com angina estável não respondedores a betabloqueadores, nitratos e bloqueadores do canal de cálcio.

Objective: To assess the cost-effectiveness analysis of trimetazidine (TMZ) associated with conventional treatment (diuretic, acetylsalicylic acid [ASA], beta blocker, angiotensin converting enzyme inhibitor (ACEI), nitrate, statine, digitalis and calcium channel antagonist) versus conventional treatment alone in the treatment of diabetic patients with stable angina non-responders to beta blockers, nitrates and calcium channel blockers from the perspective of the Public Health System (SUS). Methods: A Markov model was developed, with one year cycles, to follow the patients along the natural course of disease until the end of your lifes. Clinical data were obtained from the literature review. Unit costs were extracted from official databases. Only direct medical costs were included. Costs and benefits were discounted at a rate of 5% per year. Outcome were expressed as hospitalization due to angina pectoris (HAP) avoided. Univariate sensitivity analysis was performed to determine the parameters of greatest influence on the results, varying them by plus or minus 20% compared to the baseline scenario. Results: Treatment with TMZ showed greater benefit compared to conventional treatment and generated an Incremental Cost-Effectiveness Ratio of USD 2,225.75 per HAP avoided (1USD = 3.30BRL). The parameter with the greatest impact on outcome was the number of angina pectoris episodes. Despite the high impact, it did not change the result, keeping it cost-effective. Conclusion: TMZ associated with conventional treatment has been shown to be an effective, safe and cost-effective alternative for the treatment of diabetic patients with stable angina non-responders to beta blockers, nitrates and calcium channel blockers.