| Percutaneous coronary intervention(PCI)is the major treatment for coronary heart disease.However,postoperative adverse events greatly affect the treatment outcome of the patients,especially for those with PCI postoperative gastrointestinal bleeding.Therefore,advance research and clinical investigation should be carried out to precisely diagnosis and stratify patients to reduce the risk of this adverse event.Although in TCM clinical research field,many investigations have been done on TCM syndrome of PCI,very few studies were focused on the postoperative adverse events.There was also a lack of evidence to support using TCM treatment as preventive intervention.Here,in this study,we investigated patients who had PCI retrospectively and analysed TCM syndromes associated with PCI postoperative gastrointestinal bleeding were evaluated.The results obtained provided sufficient evidence for application of TCM treatment as preventive intervention.Furthermore,by randomized,double-blinded,parallel-controlled approach,Yiqi Zhixue treatment was evaluated to prevent gastrointestinal bleeding after PCI operation and for its effect to reduce risks of postoperative adverse cardiac events for high risk hemorrhagic patients.This thesis is consists of two parts.Part 1 Application of TCM syndrome to diagnosis patients with PCI postoperative gastrointestinal bleedingObjective:in this study,we investigated patients who had PCI retrospectively to identify high risk factors that are associated with PCI postoperative gastrointestinal bleeding.In addition,we aimed to diagnosis and stratify patients using TCM syndrome which will facilitate the prevention of PCI postoperative gastrointestinal bleeding in patients to improve prognosis from a prospective of TCM.Methods:Patients from Oct.2010 to Dec.2014 were enrolled in this study who had PCI and met the enrollment criteria.Patients who had PCI postoperative gastrointestinal bleeding were in disease group.Patients who did not have PCI postoperative gastrointestinal bleeding were in control group.By comparing these two groups of patients,we analyzed clinical characteristics,high risk factors and TCM syndromes.Results:Totally 801 patients were enrolled in this study.Among them,531 were male and 270 were female.Patients' characteristics were listed as follow:186 patients had acute ST segment elevation myocardial infarction;153 patients had acute non ST elevation myocardial infarction;342 patients had unstable angina;120 patients had stable angina pectoris.TCM syndromes were listed as follow:126 patients had syndrome of stagnant blockade of heart blood;298 patients had syndrome of blood stasis due to qi deficiency;47 patients had syndrome of stagnation of qi and blood stasis;95 patients had syndrome of intermin-gled phlegm and blood stasis;12 patients had syndrome of cold congelation and blood stasis;163 patients had syndrome of deficiency of both qi and yin;28 patients had syndrome of yin deficiency of heart and kidney;32 patients had syndrome of yang qi exhaustionAmong the 801 patients,31 patients had PCI postoperative gastrointestinal bleeding(disease group).770 patients who did not have PCI postoperative gastrointestinal bleeding were in control group.By comparing these two groups of patients,our results showed that several clinical factors were significantly different(P<0.05),including:age,gender,systolic blood pressure,serum creatinine,creatinine clearance rate,anterior descending branch lesion,and total hospitalization days.By comparing the CRUSADE score,CRUSADE 5 Classification and CRUSADE 2 Classification in these two groups,the following factors are significantly different(P<0.05):gender,creatinine clearance rate,and systolic blood pressure.Among the 31 patients in disease group who had PCI postoperative gastrointestinal bleeding,TCM syndromes were listed as follow:1 patients had syndrome of stagnant blockade of heart blood;19 patients had syndrome of blood stasis due to qi deficiency;1 patients had syndrome of stagnation of qi and blood stasis;1 patients had syndrome of intermin-gled phlegm and blood stasis;1 patients had syndrome of cold congelation and blood stasis;3 patients had syndrome of deficiency of both qi and yin;1 patients had syndrome of yin deficiency of heart and kidney;4 patients had syndrome of yang qi exhaustion.By comparing patients had syndrome of blood stasis due to qi deficiency with the patients who did not have(N=12),significant distributional difference(P<0.05)was achieved.Using single factor logistic regression method,several high risk factors were identified to have association with PCI postoperative gastrointestinal bleeding(P<0.05),including:age,BMI,gender,CRUSADE 5 Classification,CRUSADE 2 Classification,TCM syndrome(syndrome of blood stasis due to qi deficiency),vascular lesion(anterior descending branch lesion),creatinine clearance rate(CRUSADE 6 Classification),and systolic blood pressure(CRUSADE 5 Classification).Next,univariate logistic regression analysis was used as a covariate to carry out multivariate logistic regression analysis.By analyzing OR value and 95%CI,we found that patients with very high risk score(CRUSADE score>50)who had PCI postoperative gastrointestinal bleeding had OR value of 22.573 with 95%CI of(2.976,171.217).This is the most important factor that can predict PCI postoperative gastrointestinal bleeding in patients.In addition,by analyzing the TCM syndromes,patients who did not have syndrome of blood stasis due to qi deficiency had OR value of 0.3 with 95 CI of(0.14,0.645)when compared to patients who had.Therefore,these results underscored the importance of syndrome of blood stasis due to qi deficiency on the prediction of PCI postoperative gastrointestinal bleeding.Conclusion:Syndrome of blood stasis due to qi deficiency was the major TCM syndrome after PCI postoperative gastrointestinal bleeding;Syndrome of blood stasis due to qi deficiency,age,gender,systolic blood pressure and creatinine clearance rate are major high risk factors that were associated with PCI postoperative gastrointestinal bleeding;Syndrome of blood stasis due to qi deficiency was significantly correlated with PCI postoperative gastrointestinal bleeding.Part 2 Clinical investigation of Yiqi Zhixue treatment to prevent PCI postoperative gastrointestinal bleeding in high risk hemorrhagic patientsObjective:It is well known that high risk hemorrhagic patients tend to have gastrointestinal bleeding after PCI operation.However,proton pump inhibitor and anti-platelet therapy are not compatible in clinical treatment.In TCM clinical practice,Yiqi Zhixue treatment was widely used to prevent postoperative adverse events such as gastrointestinal bleeding.Therefore,based on historical TCM clinical experience,we aim to evaluate Yiqi Zhixue granules as preventive intervention of PCI postoperative gastrointestinal bleeding by randomized,double-blinded,parallel-controlled approach.It is hoped that Yiqi Zhixue treatment will effectively prevent gastrointestinal bleeding after PCI operation.In the meanwhile,we hope this treatment will reduce risks of postoperative adverse cardiac events.Methods:117 patients from Mar.2013 to Dec.2015 were enrolled in this study who had PCI operation.They met the enrollment criteria and had syndrome of blood stasis due to qi deficiency.By randomized,double-blinded,parallel-controlled approach,and utilized SAS9.2 software,we randomized these 117 patients into treatment group and control group.For patients in treatment group,standard treatment protocol was applied but with additional treatment of Yiqi Zhixue granules and placebo of pantoprazole sodium capsules.In contrast,for patients in control group,standard treatment protocol was also applied but with additional treatment of pantoprazole sodium capsules and placebo of Yiqi Zhixue granules.We assessed patients over 90 days.Major events evaluated were gastrointestinal bleeding and adverse cardiac events.Other factors evaluated were as follow:MAadp value in thrombelastogram,ADP inhibition rate,AA inhibition rate,Seattle Angina Questionnaire,improvement degree of TCM syndrome before and after treatment.In addition,the effects of Yiqi Zhixue granules as preventive intervention of PCI postoperative gastrointestinal bleeding and adverse cardiac events were also evaluated.Results:117 patients were enrolled in this study who had PCI operation and met the enrollment criteria.59 patients were randomized in treatment group,58 patients were in control group.Using statistical test,these two groups of patients were not significantly different in common clinical characteristics,past medical history,diagnosis and operational condition(P>0.05).Postoperative bleeding events:In treatment group,17 patients(28.81%)had postoperative bleeding.Using the Bleeding Academic Research Consortium(BARC)classification,11 patients(66.71%)had BRAC score of 1;5 patients(29.41%)had BRAC score of 2;1 patients(5.88%)had BRAC score of 3.As for the bleeding location,4 patients(23.53%)had gastrointestinal bleeding,8 patients(47.06%)had puncture site bleeding,1 patient(5.88%)had urinary tract bleeding,1 patient(5.88%)had cerebral hemorrhage,1 patient(5.88%)had hemoptysis and 2 patients(11.76%)had gingival bleeding.In control group,14 patients(24.44%)had postoperative bleeding.10 patients(71.43%)had BRAC score of 1;4 patients(28.57%)had BRAC score of 2;no patient had BRAC score of 3.6 patients(42.86%)had gastrointestinal bleeding,7 patients(50.00%)had puncture site bleeding,no patient had urinary tract bleeding/cerebral hemorrhage/hemoptysis and 1 patient(7.14%)had gingival bleeding.There is no significant difference between these two groups of patients in term of bleeding events(P>0.05).It is inconclusive whether these two groups are different in incidence rate of gastrointestinal bleeding.Major adverse cardiac events:In treatment group,2(3.39%)major adverse cardiac events occurred.1 patient had cardiovascular death.Another patient had target vascular reconstruction(TVR);In control group,6(10.34%)major adverse cardiac events occurred.Among them,3 patients had cardiovascular death,1 patient had recurrent unstable angina pectoris,1 patient had subacute stent thrombosis,1 patient had target vascular reconstruction(TVR).The incident rate of adverse cardiac events was lower in treatment group(6.95%lower)when compared to control group.However,this was not statistically significant(P>0.05).TCM syndrome:Patients in treatment or control group experienced similar level of uncomfortableness at Day 0 after PCI operation,including:chest pain,chest tightness,palpitations,short of breath,general lassitude and dark lip color.The tongue manifestation,pulse manifestation and overall TCM syndrome score were of no difference(P>0.05).After 7 days of treatment,obvious improvement was observed in both groups of patients for the relieve of symptoms of chest pain and tightness(P<0.05).The rest of the symptoms were only slightly improved(P>0.05).The degrees of improvement between these two groups were of no difference(P>0.05).After 30 days of treatment,significant improvement was observed in most of the symptoms and overall TCM syndrome score(P<0.05)in both groups of patients.Only pulse manifestation was not improved in control group(P>0.05).The degrees of improvement were significantly better in treatment group compared to control group(P<0.05).After 90 days of treatment,significant improvement was observed in most of the symptoms and overall TCM syndrome score in both groups(P<0.05)except for tongue manifestation and pulse manifestation in control group(P>0.05).When compared to control group,the degrees of improvement were significantly better in the relive of symptoms of palpitations,short of breath,in tongue manifestation and in overall TCM syndrome score in treatment group(P<0.05).Seattle Angina Questionnaire(SAQ):The SAQ was assessed at Day 0 and Day 30 after PCI operation.At Day 0 after operation,there was no difference in both groups for the analysis of Physical Limitations(PL),Anginal stability(AS),Anginal Frequency(AF),Treatment Satisfaction(TS),Disease Perception(DS)and overall SAQ score(P>0.05).After 30 days of treatment,significant improvement was observed in AS,AF,TS,DS and overall SAQ score(P<0.05)except for PL(P>0.05)in both treatment and control group.No significant difference was observed between these two groups(P>0.05).Thromboelastogram:At Day 7 post-operation,MAadp value,ADP inhibition rate,AA inhibition rate were of no difference between these two groups of patients.After 30 days of treatment,the MAadp value was significantly increased in control group(P<0.01).The ADP inhibition rate was significantly decreased(P<0.01).The degree of improvement was significantly different between these two groups(P<0.05).Conclusion:Yiqi Zhixue treatment was relatively effective in preventing PCI postoperative gastrointestinal bleeding in high risk hemorrhagic patients.The treatment outcome was comparable to pantoprazole sodium capsules treatment.The degree of improvement in overall TCM syndrome was significantly better in Yiqi Zhixue granules treated group compared to control group which treated by pantoprazole sodium capsules.The risk of postoperative adverse cardiac events was reduced in Yiqi Zhixue treatment.Although this comparison was not statistically significant,the optimal Yiqi Zhixue treatment will be better defined with larger patient cohort in prospective trials. |
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