Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Effect and Safety of Guanxinning Tablet () for Stable Angina Pectoris Patients with Xin (Heart)-Blood Stagnation Syndrome: A Randomized, Multicenter, Placebo-Controlled Trial.

OBJECTIVE: To investigate the effect and safety of Guanxinning Tablet (, GXN) for the treatment of stable angina pectoris patients with Xin (Heart)-blood stagnation syndrome (XBSS). METHODS: One hundred and sixty stable angina pectoris patients with XBSS were randomly assigned to receive GXN (80 cases) or placebo (80 cases, Guanxinning simulation tablets, mainly composed of lactose), 4 tablets (0.38 g/tablet), thrice daily for 12 weeks. After treatment, an exercise stress test (treadmill protocol), Chinese medicine (CM) syndrome score, electrocardiogram (ECG), and nitroglycerin withdrawal rate were evaluated and compared in the patients between the two groups. Meanwhile, adverse events (AEs) were evaluated during the whole clinical trial. RESULTS: Compared with the control group, the time extension of exercise duration in the GXN group increased 29.28 ±17.67 s after treatment (P>0.05); moreover, the change of exercise duration in the GXN group increased 63.10 ±96.96 s in subgroup analysis (P<0.05). The effective rates of angina pectoris, CM syndrome and ECG as well as nitroglycerin withdrawal rate were 81.33%, 90.67%, 45.76%, and 70.73%, respectively in the GXN group, which were all significantly higher than those in the control group (40.58%, 75.36%, 26.92%, 28.21%, respectively, P<0.05). CONCLUSION: GXN was a safe and effective treatment for stable angina pectoris patients with XBSS at a dose of 4 tablets, thrice daily.

[Treatment of sixty-one patients with coronary slow flow phenomenon by yiqi huoxue recipe combined Western drugs: a clinical research].

OBJECTIVE: To observe the clinical efficacy of treating patients with coronary slow flow phenomenon by Yiqi Huoxue Recipe (YHR) combined Western drugs, thus providing clinical evidence for further studies. METHODS: Totally 61 patients with coronary slow flow phenomenon were randomly assigned to the treatment group (31 cases) and the control group (30 cases). Patients in the control group were treated with basic treatment of Western medicine, while those in the treatment group were treated with basic treatment of Western medicine and YHR. The therapeutic course for all was two months. Clinical symptoms were observed, and electrocardiogram examinations taken, and left ventricular ejection fraction (LVEF) were evaluated before treatment and at two months after treatment. RESULTS: Patients' clinical symptoms and electrocardiogram examinations were significantly improved in the treatment group. Its effective rate of improved symptoms was 90.32% in the treatment group, superior to that in the control group (76.67%, P < 0.05). The effective rate of electrocardiogram examinations was 87.10% in the treatment group, superior to that in the control group (73.33%, P < 0.05). But there was no statistical difference in LVEF between the two groups (P > 0.05). CONCLUSION: YHR combined Western drugs could improve clinical symptoms and electrocardiographic ischemia in patients with coronary slow flow phenomenon.

[Clinical observation of the curative effect of Qiangxin Mixture on congestive heart failure].

OBJECTIVE: To investigate the efficacy of Qiangxin Mixture in patients with congestive heart failure (CHF). METHODS: Sixty cases of CHF were randomly divided into Qiangxin Mixture group (treatment group, n=30) and digoxin group (control group, n=30). The total clinical effective rate, integra of the symptoms of kidney deficiency, classification of functional capacity of the New York Heart Association (NYHA), and echocardiogram [ejection fraction (EF), cardiac output (CO), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass index (LVMI)] as well as the measurement of plasma endothelin, angiotensin II and atrial natriuretic peptide were observed in both groups. RESULTS: The total clinical effective rate of Qiangxin Mixture group was 87%, and improvement was significantly observed in the Lee CHF score, classification of functional capacity of the NYHA, EF and CO (P<0.05, vs before treatment), but no significant improvement in digoxin group (P>0.05). The integra of the symptoms of kidney deficiency, the levels of plasma ET, Ang II and ANP decreased significantly (P<0.01, vs before treatment and digoxin group respectively). IVST, PWT and LVMI were also reduced significantly (P<0.01, vs before treatment; P<0.05 vs digoxin group). CONCLUSION: The Qiangxin Mixture is effective in enhancing cardiac contraction, improving hemodynamics in the short-term and rectifying some indexes in the long-term, so it could postpone the processes of CHF. This mechanism may be related to decreasing the stimulating factors (angiotensin, endothelin) which trigger the cardiac remodeling, delaying or reversing the cardiac remodeling.