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.
Humans ; Medicine, Chinese Traditional ; Angina, Stable/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

OBJECTIVETo observe the clinical efficacy and safety of Xinluotong Tablet (XLTT, with actions of benefiting qi, activating blood, and supplementing Shen) in treatment of stable coronary heart disease angina patients of qi deficiency and blood stasis syndrome.

METHODS240 stable coronary heart disease angina patients of qi deficiency and blood stasis syndrome were randomly assigned to the trial group and the control group, 120 in each group. The trial group was treated with XLTT, four tablets each time, three times a day, while the control group was treated with Yangxinshi Tablet (YXST), three tablets each time, three times a day. The double blinded treatment lasted for four weeks. The therapeutic effects on angina, electrocardiogram (ECG), the exercise test, the improvement of Chinese medicine syndromes, and the safety index were observed.

RESULTSThe trial group was superior to the control group after treatment in aspects of the therapeutic effects on angina (91.45% vs 84.87%) and the ECG (65.81% vs 55.46%), but with no statistical difference (P>0.05). There was no statistical difference in the the exercise test or the improvement of Chinese medicine syndromes (P>0.05). No adverse reaction occurred during the therapeutic course.

CONCLUSIONXLTT was safe and effective in treatment of stable coronary heart disease angina patients of qi deficiency blood stasis syndrome.

Aged ; Angina Pectoris ; drug therapy ; Angina, Stable ; drug therapy ; Coronary Disease ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Tablets

OBJECTIVETo systematically assess the efficacy and safety of Rhodiola in treating chronic stable angina pectoris.

METHODSOur group searched the Cochrane library, PubMed, Embase, Chinese biomedical literature database (CBM), VIP database (VIP), Chinese Journal Full-text Database (CNKI) for the literature published in English and Chinese till April 2013. Randomized controlled trials (RCTs) were included on the therapeutic effect of Rhodiola or Rhodiola plus conventional Western medicine in comparison with the conventional Western medicine treatment on stable angina. Data were extracted according the data extraction form. The literature methodological quality was assessed by using the Cochrane handbook, and data analyzed by Rev-Man 5.2 Software for Meta-analysis. The effect indicators of outcomes was expressed by odds ratio (OR) and 95% CI.

RESULTSA total of 7 randomized controlled trials, 662 cases of stable angina pectoris patients met the inclusion criteria and all published in Chinese, without one scientific design and high quality literature. Compared with the conventional Western medicine treatment, combined with oral administration of Rhodiola could improve the efficiency of anti-angina (OR = 2.49, 95% CI: 1.02 - 6.09). Combined with intravenous infusion of Rhodiola could also improve the efficacy of angina pectoris (OR = 4.86, 95% CI: 2.4 - 9.82). Oral administration of Rhodiola couldn't improve ECG efficacy (OR = 1.25, 95% CI: 0.67 - 2.34). Intravenous infusion of Rhodiola could improve the clinical efficacy (OR = 2.94, 95% CI: 1.61 - 5.35). Combined with the conventional treatment, intravenous infusion of Rhodiola could improve the whole blood viscosity (low and high shear rates) and inverse variance (IV) (-1.36 and -0.99, 95% CI: -1.65 - 1.07 and -1.26 - 0.71), but could not reduce serum fibrinogen and D-dimer level. The incidence rate of adverse reactions was higher than that of the conventional treatment combined with Rhodiola (OR = 0.1, 95% CI: 0.02 - 0.51).

CONCLUSIONSOn the basis of routine treatment, Rhodiola could further improve patients' symptoms. Combined with intravenous medication, Rhodiola could increase the ECG improvement rate, and reduce adverse reactions. But the methodological quality of included studies was poor, the number of samples was small, and influence factors such as the intervention period was short. This conclusion needs scientific and rational design in a larger sample, multicenter clinical trial to verify.

Angina, Stable ; drug therapy ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Randomized Controlled Trials as Topic ; Rhodiola ; Treatment Outcome

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).
Acupuncture Points ; Angina, Stable/drug therapy* ; China ; Drugs, Chinese Herbal/adverse effects* ; Female ; Humans ; Male ; Treatment Outcome

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.
Humans ; Angina, Stable/drug therapy* ; Medicine, Chinese Traditional ; Network Meta-Analysis ; Drugs, Chinese Herbal ; Salvia miltiorrhiza ; Cholesterol

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).
Angina, Stable ; drug therapy ; physiopathology ; Coronary Circulation ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Exercise Test ; Exercise Tolerance ; physiology ; Humans ; Placebos ; Sample Size

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.
Adjuvants, Pharmaceutic ; Angina, Stable ; drug therapy ; C-Reactive Protein ; analysis ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Electrocardiography ; Humans ; Lipids ; blood ; Randomized Controlled Trials as Topic

PURPOSE: It is unknown whether cilostazol pretreatment reduces postprocedural myonecrosis (PPMN). Cilostazol pretreatment reduces PPMN after percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A total of 120 patients with stable angina scheduled for elective PCI were randomly assigned to a 7-day pretreatment with Cilostazol (200 mg/day) or to a control group. Creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) levels were measured at baseline and at 6 and 24 hours after PCI. The primary end-point was the occurrence of PPMN, defined as any CK-MB elevation above the upper normal limit (UNL). Aspirin and clopidogrel were co-administered for 7 days before PCI, and resistance to these agents was then assayed using the VerifyNow System. RESULTS: There was no difference in baseline characteristics between the final analyzable cilostazol (n=54) and the control group (n=56). Despite a significantly greater % inhibition of clopidogrel in the cilostazol group (39+/-23% versus 25+/-22%, p=0.003), the incidence of PPMN was similar between the cilostazol group (24%) and the control group (25%, p=1.000). The rate of CK-MB elevation at > or =3 times UNL was also similar between the two groups (6% versus 5%, p=0.583). The incidence of cTnI increase over the UNL or to 3 times the UNL was not different between the two groups. There was no significant difference in terms of the rate of adverse events during follow-up, although the cilostazol group showed a tendency to have a slightly higher incidence of entry site hematoma. CONCLUSION: This trial demonstrated that adjunctive cilostazol pretreatment might not significantly reduce PPMN after elective PCI in patients with stable angina.
Aged ; Angina, Stable/drug therapy/enzymology/therapy ; Angioplasty, Balloon, Coronary/*adverse effects ; Creatine Kinase, MB Form/blood ; Female ; Heart Injuries/etiology/prevention & control ; Humans ; Male ; Middle Aged ; Myocardium/pathology ; Necrosis ; Phosphodiesterase 3 Inhibitors/*administration & dosage ; Prospective Studies ; Tetrazoles/*administration & dosage

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 (VO_2max) 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, VO_2maxand 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.
Androgens/therapeutic use* ; Angina, Stable/drug therapy* ; Body Composition ; C-Reactive Protein ; Calcium Channel Blockers/therapeutic use* ; Cardiovascular Diseases/prevention & control* ; Chronic Disease ; Coronary Circulation ; Cytokines ; Exercise Tolerance ; Glucose/metabolism* ; Heart Failure/drug therapy* ; Humans ; Insulin Resistance ; Lipid Metabolism ; Male ; Muscle Strength ; Oxygen Consumption ; Pulmonary Circulation ; Randomized Controlled Trials as Topic ; Testosterone/therapeutic use* ; Vascular Resistance ; Vasodilation