Long-term Use Of Heart-protecting Musk Pill Treatment Of Coronary Heart Disease Long-term Efficacy Evaluation

BackgroundShexiang Baoxinwan has been used in treating coronary heart disease(CHD) for over thirty years.Its effects on releasing angina pectoris has been conformed through long time clinical use.A plenty of researches have demonstrated its multiple mechanisms,which involved vasodilation,oxyradical clearance,improving endothelial function, facilitating angiogenesis.These mechanisms transform the administration of SXBXW from an emergency form to a long-term use.It proved SXBXW 2 pills oral three times daily for long-term(6 months) presented a favorable tolerability and safety in the CHD patients.However,how about the clinical effect of the addition of SXBXW 2 pills oral three times daily for long-term(at least 6 months) to conventional treatment in coronary heart disease? This study will provide a clinical evidence.Objective1.To evaluate the effect of long-term using SXBXW on cardiovascular events.2.To observe the improvement effect on the endothelial function of SXBXW's long-term administration to CHD patients for probing into the pathophysiological mechanism of its clinical effectMethodsThe clinical trial was a randomized non-blind parallel controlled study in the first 6 months.Then it became a cohort study.Clinical effect study:The study group was comprised of 200 patients with CHD,which came to the department of cardiology of Huashan Hospital between May 2005 and Jun.2006.After their subscription to the informed consent,they were randomly arranged into the intensive group(conventional CHD therapy+SXBXW 2 pills,po.tid.,at least 6 months) and the conventional group(conventional CHD therapy)(1:1).After 6 months, patients of the intensive group could choose their therapy from continuous taking SXBXW(keep or decrease dose) or stopping taking the pills.The patients in conventional group maintained their former therapy.The follow-up ended on January 31^st,2008.All of the clinical events and treatment were recorded at least once three months.The primary endpoint was a composite of cardiovascular morbidity and mortality.Endothelial Function Study:80 eligible patients were chosen from the above study's objects which inclusing criteria of endothelial function study.They were also randomly arranged into the intensive group and the conventional group(1:1),with a follow-up of 6 months.The brachial artery endothelial function was detected by vascular ultrasound at the time of admission,the end of the 3^rd month and the end of the 6^th month. Meanwhile,the factors related to the endothelial function in blood were also detected,which involved nitrogen monoxidum(NO),nitricoxide synthase(NOS),superoxide dismutase(SOD),endothelin(EW).The study detected these indexes at the end of the 18^th month.The intensive group was devided into the six-month-therapy group and the continuous group.Comparisons of all the indexes were carried out among the three groups and between the end of the 18^th month and the end of the 6^th month in each group.ResultsClinical effect study:After a median follow-up of 2.25 years(range 0.5 to 2.75) all clinical events(23 vs33),primary clinical events(20 vs29) and angina pectoris events(9 vs19) were recorded in fewer individuals which taking SXBKW as an ancillary treatment than the patients given conventional treatment(P＜0.05).The events such as all-cause death(2 vs5),cardiovascular death(1 vs2),congestive heart failure(3 vs4), stroke(2 vs4),the need for percutaneous coronary intervention and coronary artery bypass grafty(2 vs4) and other clinical events(5 vs6) were also recorded in fewer individuals,but there were no significant changes between the two groups(P＜0.05).It also shows the use of nitrates declined significantly during SXBIXW long-term treatment.Endothelial Function Study:1.endothelial-dependent flow-mediated vasodilatation(FMD): Comparisons in each group:in the Conventional Group:comparing the 18^th month-end value to the 6^th month-end one,although the FMD became lower,there's no obvious change(10.66±4.94vs11.76±4.60,P＞0.05).in the Six-month-therapy Group:comparing the 18^th month-end value to the 6^th month-endone,there's also no obvious change(11,10±5.28 vs12.58±4.57,P＞0.05).in the Continuous Group:comparing the 18^th month-end value to the 6^th month-end one,although the FMD was improved,there's no significant difference(14.19±4.33vs12.58±4.57,P＞0.05).Comparisons among the three groups:At the end of the 18^th month,the Continuous Group's FMD was distinctly higher than the Conventional Group's(P＜0.05),the Six-month-therapy Group's FMD was between them and was closer to the Conventional Group's,but there was no significant difference(P＞0.05).2.NO,NOS,SODComparisons in each group:in the Conventional Group:The NO,NOS and SOD all raised slightly at the end of the 18^th month in comparison with the values detected at the end of the 6^th month(NO:73.00±33.37vs71.92±62.26;NOS:32.10±5.85vs31.33±21.21;SOD:32.10±5.85vs31.33±21.21),but there's no significant difference(P＞0.05).in the Six-month-therapy Group:The NO became lower slightly when the NOS and SOD declined significantly at the end of the 18^th month in comparison with the values detected at the end of the 6^th month(NO:100.67±44.72 vs125.22±76.71,P＞0.05;NOS:36.28±5.33 vs47.16±16.25,P＜0.001;SOD:81.72±4.48 vs92.50±15.21,P＜0.001).in the Continuous Group:The NO raised when the NOS and SOD declined at the end of the 18^th month in comparison with the values detected at the end of the 6^th month(NO:134.34±67.84 vs125.22±76.71;NOS:46.99±7.75 vs47.16±16.25;SOD:87.22±6.40 vs92.50±15.21),but there's no significant difference(P＞0.05).Comparisons among the three groups:At the end of the 18^th month,the three indexes of the Continuous Group were higher respectively than which of the Conventional Group.The NOS of the Six-month-therapy Group was lower obviously(P＜0.01) than which of the Continuous Group while no changes had been found of NO or SOD of the group in compassion with the other two groups(P＞0.05).3.ETComparisons in each group:comparing the 18^th month-end value to the 6^th month-end one,although the ET level became higher,there's no obvious change in each group(the Conventional Group:103.24±37.68 vs101.15±28.99;the Six-month-therapy Group:92.64±36.39 vs84.71±28.43;the Continuous Group:87.75±25.81 vs84.71±28.43,P＞0.05)Comparisons among the three groups:At the end of the 18^th month,the Continuous Group's ET was higher than the Conventional Group's,the Six-month-therapy Group's ET was between them and was closer to the Conventional Group's,but there were no obvious changes between every two groups(P＞0.05).Conclusion1.The addition of SXBXW 2 pills oral three times daily for long-term (at least 6 months) can decrease more angina pectoris events and reduced more nitrates use than conventional treatment in patients with coronary heart disease.2.The addition of SXBXW 2 pills oral three times daily for long-term (at least 6 months) to conventional treatment prevented more clinical events.It also showed a trend to prevent more all-cause death and cardiovascular death,congestive heart failure events,stroke events and the need for percutaneous coronary intervention or coronary artery bypass grafty,which need further research of large-sample clinical trial to prove.3.SXBXW 2 pills oral three times daily for long-term(at least 6 months) could improve endothelial function in the CHD patients significantly, which could not been maintained to stop taking the pills for 12 months.This pharmacological effect may be one of the mechanism for SXBXW's clinical effect on preventing angina pectoris.