| Background:Coronary heart disease(CHD),with an increasing prevalence and mortality rate is a most commonly seendisease that poses great threaten to human health.A large number of experimental and clinical evidence has demonstrated that chronic inflammation plays a critical role in the development of atherosclerosis(AS)and occurrence of cardiovascular events.Therefore,strategies for treatment and prevention of atherosclerotic diseases including CHD should not be limited to lipid lowering.Inflammation controlling should also be considered.According to traditional Chinese medicine(TCM)theory,inflammation and the following process of plaque rupture in AS is closely associated with toxin theory.One the basis of TCM theory about blood stasis and toxin and new mechanism of CHD,our research team led by academician Keji Chen firstly put forward the hypothesis that transformation of toxin from blood-stasis and the combination of toxin and stasis may lead to cardiovascular events in stable CHD patients.Then we confirmed the blood stasis and toxin theory and established criteria for toxic differentiation in stable CHD patients by performing systematic literature reviewing,clinical and experimental research under support of the national 973 project,laying the foundation for early identification and intervention of high-risk patients with stable coronary heart disease.In the established criteria,the abnormal elevation of high sensitivity C reactive protein(hs-CRP)is regarded as one of the main components,Qing-xin-jie-yu Decoction is simplified from academician Keji Chen classic Yu-geng-tong-yu Decoction,and consists of Astragalus,salvia,chuanxiong,ageratum,Rhizoma Coptidis.Thus,it can tonify Qi,activating blood,removing phlegm,eliminating toxin,and can be regarded as the representative formula of blood stasis and toxin theory." Previous studies have demonstrated that the classic prescription of Yu-geng-tong-yu Decoction can significantly relieve angina,reduce the incidence of stroke and readmission due to angina,heart failure,arrhythmia within 6 months and improve the quality of life of patients with unstable angina pectoris.Whether the addition of Qin-xin-jie-yu Decoction to conventional treatment guided by the blood stasis and toxin theory can effectively treat stable CHD patients with chronic inflammation is well worth exploring.Objectives:Guided by principles of evidence-based medicine,a randomized,double-blind,placebo-controlled clinical trial was conducted with hs-CRP and other inflammatory markers as primary outcome.We aimed to objectively assess the efficacy and safety of Qing-xin-jie-yu Decoction for stable CHD patients with chronic inflammation and further verify the "blood stasis and toxin" pathogenesis hypothesis,which,ultimately,will prove advantages of TCM in the treatment of stable CHD patients.Method:This study is a randomized,double-blind,placebo-controlled clinical trial.The random number was generated by the SAS 9.2 software,and the random sequence was kept by a person independent of the trial,who will perform the "remote" random sequence concealment.72 eligible stable CHD patients were randomly allocated in a 1:1 ration into treatment(n=36)or control group(n=36).Patients from treatment group received Qing-xin-Jie-yu Decoction and conventional therapy for 6 months,while patients for the control group received placebo and conventional therapy.Changes of concentration of hs-CRP and other inflammatory cytokines including interleukin-6(IL-6),tumor necrosis factor A(TNF-a),CD40 ligand(sCD40L)antigen,soluble vascular cell adhesion molecule(sVCAM-1),and matrix metalloproteinase-9(MMP-9),TCM symptoms,angina grade,blood stasis score and the self-rating Depression Scale(SDS)were recorded and compared between the two groups.Results:Per-protocol set(PPS)which included 34 cases from the treatment group and 35 cases from the control group.1.The baseline character before treatment including gender,age,BMI,number of diseased vessels,risk factors,blood pressure,heart rate,blood routine,liver function,renal function,blood coagulation function,combined medication was comparable between the two groups(P>0.05)2.The TCM syndromes of the included 69 stable CHD are mainly phlegm syndrome,blood stasis syndrome,qi stagnation syndrome,cold syndrome,qi deficiency syndrome,yin deficiency syndrome,yang deficiency syndrome.There are 49 cases of phlegm syndrome(accounting for 70.01%),51 cases of blood stasis syndrome(73.91%),14 cases of qi stagnation syndrome(20.29%),7 cases of cold syndrome(10.14%),42 cases of qi deficiency syndrome(60.87%),16 cases of yin deficiency syndrome(23.19%),10 cases of yang deficiency(6.9%),and no yang collapse syndrome.The distribution of TCM syndrome was as follows:blood stasis syndrome>phlegm syndrome>qi deficiency syndrome>yin Deficiency syndrome>qi stagnation syndrome>cold syndrome>yang deficiency syndrome.According to the toxin differentiation criteria for stable CHD patients,there are 61 patients differentiated as toxin syndrome(88.41%).Analysis of syndrome factors of toxinsyndrome showed that the blood stasis syndrome(50 cases,81.97%),phlegm syndrome(47 cases,77.05%)and qi deficiency syndrome(41 cases,67.21%)were the most common syndrome followed by qi stagnation syndrome(18.03%),yin deficiency syndrome(24.60%),yang deficiency(16.39%),cold syndrome(0.08%).3.After 6 months of treatment,hs-CRP,IL-6 level of both groups was significantly lowered,and the lowered value was much more in the treatment group than the control group(2.28mg/L vs 1.10 mg/L,P=0.026<0.05 for hs-CRP,167.60 pg/ml vs 51.76 pg/ml,P=0.016<0.05)After treatment,the levels of sCD40L and MMP-9 were significantly lower than those of the control group(P<0.01).sCD40L concentration of the treatment group decreased 71.15 pg/ml(P<0.01),while control group decreased-147.09 pg/ml;MMP-9 level in the treatment group decreased 0.53ng/ml,while control group decreased-0.03 ng/ml4.After 6 months of treatment,chest pain and chest tightness of both the treatment and control group were significantly relieved,and the effect size of treatment group is better than the control group(P=0.007<0.01).Palpitation was significantly relieved in both groups after treatment(P=0.005/P=0.003),but co mparison between the two group showed no significant difference(P=0.856>0.05).In addition,angina grade,blood stasis score and SDS were both lower in the treatment group than the in treatment group(P<0.01/P<0.05).5.Safety evaluation:one patient in the treatment group suffered diarrhea,and two patients in the control group suffered dizziness and palpitation respect-ively.However,none of them discontinued the allocated therapy.The adverse event rate for dizziness,diarrhea and palpitations respectively,analyzed in the safety sets(SS)were 1.4%.Conclusion:On the basis of conventional treatment,the addition of Qing-xin-jie-yu Decoction can further reduce the serum concentration of hs-CRP and other inflammatory factors such as IL-6,MMP-9 and sCD40L in stable CHD patients with chronic inflammation,suggesting that Qing-xin-jie-yu decoction can effectively inhibit the inflammatory response.Qing-xin-jie-yu Decoction can also improve angina pectoris,blood stasis-score,chest pain,chest tightness,SDS score and other clinical symptoms,which may be due to its anti-inflammatory effects.No bleeding event or other serious adverse-event was reported.However,whether Qing-xin-jie-yu Decoction can improve the prognosis of stable CHD patients with chronic inflammation remains to be answered by further multicenter,large sample,randomized controlled trial. |
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