The effectiveness and safety of Chinese Patent Medicines based on syndrome differentiation in patients following percutaneous coronary intervention due to acute coronary syndrome (CPM trial): A nationwide Cohort Study.

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.

Xinyue Capsule in patients with stable coronary artery disease after percutaneous coronary intervention: a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Xinyue capsule, a patented Chinese herbal medicine, has been used to manage coronary artery disease (CAD) for over a decade in China, but whether it can further reduce risk of cardiovascular events beyond conventional treatment is unknown. METHODS: In this multicenter, randomized, placebo-controlled trial, we randomly assigned patients with stable CAD who underwent percutaneous coronary intervention (PCI) within the preceding 3-12 months to receive Xinyue capsule (100 mg panax quinquefolius saponins, three times a day) or placebo for 24 weeks in addition to conventional treatment. The primary endpoint was a composite that included cardiac death, nonfatal myocardial infarction and urgent revascularization with either PCI or coronary artery bypass grafting. The secondary composite endpoints included stroke, re-hospitalization due to acute coronary syndrome (ACS), pulmonary embolism, peripheral vascular events and all-cause mortality. Quality of life was assessed using a 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 1054 participants were included in the analyses. The median follow up was 1 year. The primary endpoint events occurred in 16 patients (3.02%) in the Xinyue group and 34 patients (6.49%) in the placebo group (hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.25 to 0.825; P = 0.009). Secondary end-point events occurred in 5.47% of patients in the Xinyue group and 10.31% in the placebo group (HR 0.515, 95% CI 0.328 to 0.809; P = 0.004). SF-36 subscale scores at 12 months were significantly higher in the Xinyue group than placebo group for general health (P = 0.048) and vitality (P = 0.008). CONCLUSIONS: In patients with stable CAD after PCI within the preceding 3 to 12 months, Xinyue capsule added on conventional treatment reduced the incidence of primary composite endpoint (cardiac death, nonfatal myocardial infarction and urgent revascularization).

The efficacy of Chinese herbal medicines on acute coronary syndrome with renal insufficiency after percutaneous coronary intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Chuanxiong capsule consists of Angelica sinensis radix and Chuanxiong rhizome, which are used in the traditional Chinese medicine for the treatment of coronary artery disease, and Xinyue capsule is composed of panax quinquefolius saponin extracted from leaves and stems of Panax quinquefolium L, which has the functions of anti-myocardial ischemia, improving myocardial energy metabolism and inhibiting apoptosis of cardiomyocytes. OBJECTIVE: To observe the role of Chinese herbal medicines in the cardiovascular outcome among patients with acute coronary syndrome (ACS) and renal insufficiency after percutaneous coronary intervention (PCI). METHODS: The subjects came from the 5C trial (chictr.org number: chictr-trc-07000021), post-PCI patients suffered from ACS with mild-to-moderate renal insufficiency (30 mL•min-1•1.73 m-2 < estimated glomerular filtration rate≤89 mL•min-1•1.73 m-2) included. The study population consisted of 215 subjects in the control group who were treated with western medicine standard therapy, and 211 subjects in the treatment group who were treated with Chinese herbal medicines (Fufang Chuanxiong Capsule and Xinyue Capsule) for 6 months on the basis of western medicine standard therapy. All were followed for 1 year. The primary endpoint included the composite of cardiac death, nonfatal recurrent myocardial infarction, and ischemia-driven revascularization. Secondary endpoint included the composite of stroke, congestive heart failure, and readmission for ACS. The serum creatinine and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After 1 year follow-up of two groups, there were 16 cases of primary endpoint in the control group and 6 cases of primary endpoint in the treatment group [absolute risk reduction (ARR): 0.046, 95%CI: 0.004-0.088; relative risk (RR): 0.38, 95%CI: 0.15-0.96, P = 0.040]. There were 15 cases of secondary endpoint in the control group and 5 cases of secondary endpoint in the treatment (ARR: 0.041, 95%CI: 0.006-0.086; RR: 0.34, 95%CI: 0.13-0.92, P = 0.033). The eGFR in the treatment group was significantly higher than that in the control group (75.19 ±â€¯16.74 mL min-1·1.73 m-2 VS 72.03 ±â€¯14.96 mL min-1·1.73 m-2, P < 0.05). The eGFR in the treatment group was significantly higher after the intervention with Chinese herbal medicines than that before intervention (72.27 ±â€¯11.83 mL min-1·1.73 m-2 VS 75.19 ±â€¯16.74 mL min-1·1.73 m-2, P < 0.05). CONCLUSION: Chinese herbal medicines plus western medicine standard therapy improved clinical outcomes in patients with ACS and mild-to-moderate renal insufficiency. Additionally, this study also demonstrated Chinese herbal medicines were useful in deferring decline of renal function.

Qing-Xin-Jie-Yu Granule for patients with stable coronary artery disease (QUEST Trial): A multicenter, double-blinded, randomized trial.

BACKGROUND AND AIM: Despite optimal secondary preventive treatment, patients with stable coronary artery disease (SCAD) remain at high risk of cardiovascular events. This multicenter, double-blinded, randomized trial sought to determine whether the addition of Qing-Xin-Jie-Yu Granule (QXJYG), a traditional Chinese medicine prescription, to standard therapy would further reduce risk of cardiovascular events in patients with SCAD. METHODS: A total of 1500 patients with documented SCAD were randomly assigned in a 1:1 ratio to QXJYG or placebo for 6 months, and followed up for another 6 months. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction (MI) and coronary revascularization. Near the end of the trial, but before unblinding, a commonly used composite 'hard' endpoint composed of cardiovascular death, nonfatal myocardial infarction and ischemic stroke was additionally analyzed. RESULTS: During a median follow-up of 12 months, no significant difference of the primary outcome between the two groups was observed (1.59% vs. 1.62%; hazard ratio, 0.41; 95% CI, 0.13-1.28). However, absolute risk of the composite 'hard' endpoint was reduced by 0.99% (0.31% vs. 1.30%; hazard ratio, 0.06; 95%CI, 0.01 to 0.53). No difference of adverse events between the two groups was observed. CONCLUSION: In patients with SCAD, the addition of QXJYG to standard therapy was associated with reduced risk of nonfatal MI and the composite 'hard' endpoint of cardiovascular death, nonfatal MI and stroke. (http://www.chictr.org.cn/showproj.aspx?proj=5200, ChiCTR-TRC-13004370).

Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity.

BACKGROUND: Cardiac atrophy and reduced cardiac distensibility have been reported following space flight. Cardiac function is correspondingly regulated in response to changes in loading conditions. Panax quinquefolium saponin (PQS) improves ventricular remodeling after acute myocardial infarction by alleviating endoplasmic reticulum stress and Ca2+overload. However, whether PQS can ameliorate cardiac atrophy following exposure to simulated microgravity remains unknown. PURPOSE: To explore the protective role of PQS in cardiac remodeling under unloading conditions and its underlying mechanisms. METHODS: Hindlimb unloading (HU) model was used to simulate unloading induced cardiac remodeling. Forty-eight male rats were randomly assigned to four groups, including control, PQS, HU and HU + PQS. At 8 weeks after the experiment, cardiac structure and function, serum levels of Creatine Kinase-MB (CK-MB), Cardiactroponin T (cTnT), ischemia modified albumin (IMA), and cardiomyocyte apoptosis were measured. Network pharmacology analysis was used to predict the targets of the six major constituents of PQS, and the signaling pathways they involved in were analyzed by bioinformatics methods. Changes in the key proteins involved in the protective effects of PQS were further confirmed by Western Blot. RESULTS: Simulated microgravity led to increases in serum levels of CK-MB, cTnT and IMA, remodeling of cardiac structure, impairment of cardiac function, and increased cardiomyocyte apoptosis as compared with control. PQS treatment significantly reduced serum levels of CK-MB, cTnT and IMA, improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis induced by unloading. The activation of AMPK and inhibition of Erk1/2 and CaMKII/HDAC4 were demonstrated in the cardiocytes of HU rats after PQS treatment. CONCLUSION: PQS provides protection against cardiac remodeling induced by simulated microgravity, partly resulting from changes in the signaling pathways related to energy metabolism reduction, calcium overloading and cell apoptosis.

Long-term follow-up of Chinese herbal medicines combined with conventional treatment in patients with acute coronary syndrome after percutaneous coronary intervention: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events. RESULTS: A total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group). CONCLUSION: CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

[Efficacy of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus after Percutaneous Coronary Intervention: a Clinical Observation].

OBJECTIVE: To observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI). METHODS: In this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment. RESULTS: The incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01). CONCLUSION: Administration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI.

Long-term effect of stent coating with zedoary essential components on neointimal formation in the porcine coronary artery.

OBJECTIVE: To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation. METHODS: ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects. RESULTS: ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group. CONCLUSION: The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease Patient Identified with Proteomic Method.

Objective. This trial aims to look for the protein biomarker of "toxin syndrome" of CHD patients. Methods. We have performed two trials in this paper. The first trial was a randomized controlled trial (RCT) of the plasma proteome in unstable angina (UA) patients by Maldi-Tof Mass. The second trial was a nested case-control study in 1503 stable CHD patients with one-year followup for acute cardiovascular events (ACEs). Results. In the RCT study, 12 protein spots were found to be the differential protein for the significant differences between the difference of before and after treatment in group A and group B; 2 of them (3207.37 Da and 4279.95 Da) was considered to be unique to "toxin syndrome" for being differential proteins of group B but not group A. These 2 spots were identified as Isoform 1 of Fibrinogen alpha chain precursor (FGA, 3207.37 Da) and Isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 4279.95 Da), respectively. In the nested case-control study, the result of Western blot demonstrated that protein expression of ITIH4 in the group with followup ACEs was significantly lower than the matched group without followup ACEs (P = 0.027). Conclusion. ITIH4 might be a new potential biomarker of CHD "toxin syndrome" in TCM, indicating the potential role in early identifying high-risk CHD patients in stable period.

Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study.

Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.

[Correlation between blood stasis syndrome and pathological characteristics of coronary artery in patients with coronary heart disease].

OBJECTIVE: To study the correlation of blood stasis syndrome or its accompanied syndromes with Gensini score in patients with coronary heart disease (CHD) in stable condition. METHODS: The syndrome types of traditional Chinese medicine (TCM) and blood stasis score in 131 CHD patients confirmed by coronary angiography were recorded. Gensini score was calculated according to the coronary pathological characteristics showed by angiography. The correlations of blood stasis syndrome and its accompanied syndromes with coronary lesion and Gensini score were analyzed. RESULTS: Among the TCM syndrome types, blood stasis, turbid phlegm and qi deficiency were the most common syndromes, revealed in 85 patients (64.9%), 83 patients (63.4%) and 85 patients (64.9%), respectively. The coronary lesion length and Gensini score in the patients with blood stasis syndrome were much higher than those in the patients with non-blood stasis syndrome (P<0.05 or P<0.01). In the subtypes of blood stasis, the coronary lesion length and Gensini score in the patients with blood stasis accompanied by turbid phlegm syndrome were higher than those in the patients with non-blood stasis syndrome (P<0.05). And in the patients whose blood stasis syndrome score was more than 9 points, the coronary lesion length was higher than that in the patients whose blood stasis syndrome score was less than 9 points (P<0.05). Besides, with bivariate analysis, the blood stasis syndrome score showed no correlation with Gensini score (Pearson correlation coefficient was 0.104, P=0.241). CONCLUSION: Blood stasis syndrome is the most common TCM syndrome in CHD patients in stable condition. The blood stasis syndrome score is proportional to coronary lesion length, and reflects the severity of coronary lesion.