The Risk Of Upper Gastrointestinal Bleeding In Patients Taking Traditional Chinese Medicine Patent Prescription: A Case-control Study

BackgroundHuo Xue Hua Yu medicines,a category of Chinese patent medicines which promote blood circulation to remove blood stasis,belong to Traditional Chinese Medicine that regulates blood condition.This category of medicines,which can dissipate blood stasis,clear and activate the channels and collaterals,are used as supplementary medicines to anti-platelet aggregation medicines and anticoagulation medications.Their effectiveness in the treatment of cardiovascular and cerebrovascular diseases has been gradually recognized.Some common medication of this category,including salvia ligustrazine injection,safflower yellow injection and breviscapine injection,are used in hospital for the treatment of cardiovascular and cerebrovascular diseases.Recent years,their consumptions always rank at the top in medicines list of most domestic hospitals.However,as the widely using or even abusing of this category of medications,their side effects and safety problems,which is more and more common in the clinical work,are causing concerns in clinical work.Digestive tract damages are common side effects of these medicines.Severe case may experience gastric or intestinal hemorrhage,which lead to melena,hematochezia,occult blood positive and anemia.There are no systematic report and study on the relationship between digestive tract hemorrhages and use of Huo Xue Hua Yu medicines.It have been proven in many clinical reports that use of anti-platelet aggregation medication(including aspirin and clopidogrel)and anticoagulation medication(including warfarin and Non-selected non-steroidal anti-inflammatory drugs)are risk factors of digestive tract hemorrhage.In clinical work,Huo Xue Hua Yu medicines combined with anti-platelet aggregation medicines and anticoagulation medicines are always used in the treatment of cardiovascular and cerebrovascular diseases.The question whether using Huo Xue Hua Yu medicines alone would lead to digestive tract hemorrhages and whether Huo Xue Hua Yu medicines would increase the risk of hemorrhage when combined with anti-platelet aggregation medicines and anticoagulation medicines,are causing concern among experts in gastroenterology field.Objective1.To investigate the connection between upper gastrointestinal bleeding(UGIB)and using of the Huo Xue Hua Yu injection,low dose aspirin(LDA),clopidogrel,warfarin and Non-selected non-steroidal anti-inflammatory drugs(ns NSAIDs),respectively.2.To investigate whether Huo Xue Hua Yu injections would increase the risk of UGIB when combined with LDA,clopidogrel,warfarin and ns NSAIDs,respectively.MethodsThis is a Case-control study.Clinical data of 920 upper gastrointestinal hemorrhage patients,who were hospitalized in the Xinqiao Hospital,Third Military Medical University,Chongqing from Jan.2010 to Jan.2015,were collected as case group from the clinical database of the hospital.Clinical data of 1840 patients,who had no gastrointestinal hemorrhage during hospitalization and chosen according to their gender and department from the database by MATLAB 2014,were collected as control group.Adjusted OR was calculated using stepwise logistic regression analysis.It was regarded as a risk factor when adjusted OR > 1.00 and P <0.05 was regarded as statistical significance.It was regarded as a protect factor when adjusted OR < 1.00 and P <0.05 was regarded as statistical significance.Results1.Younger age was a protect factor of UGIB in patients compared with the advanced age group(age≥65 years old).The risky factors of UGIB were smoking,Helicobacter Pylori infection,history of gastrointestinal hemorrhage,digestive ulcer,chronic gastritis,chronic duodenitis,cerebrovascular diseases,diabetes and malignant tumor.History of alcohol intake and gastroesophageal reflux disease could not be deduced as risky factors of UGIB in our study.2.Huo Xue Hua Yu medicines increased the risk of UGIB.The adjusted OR was 1.640(95%CI=1.258-2.137,P<0.001).LDA,clopidogrel,warfarin,ns NSAIDs,akafen powder,corticosteroid hormone and spirolactone were independent risk factors of UGIB,respectively.Proton pump inhibitor and histamine 2 receptor antagonists were protecting factor of UGIB.Calcium antagonist and nitrate could not be deduced as risky factors of UGIB in our study(P>0.05).3.Huo Xue Hua Yu injection combined with LDA increased the risk of UGIB(adjusted OR=4.193,95% CI 2.471-7.114,P﹤0.001).Huo Xue Hua Yu injection increased risk of UGIB combined with clopidogrel,heparin,spirolactone and nitrate respectively.Huo Xue Hua Yu injection decreased the risk of UGIB combined with proton pump inhibitor.4.Patients with history of gastrointestinal hemorrhage or peptic ulcer have a higher risk of UGIB after using Huo Xue Hua Yu injection,LDA or clopidogrel.However,we could not found that patients with helicobacter pylori infection had a higher risk of UGIB when using of Huo Xue Hua Yu injection at the same time.ConclusionTraditional Chinese Medicine patent prescription,which has effect of dispersing blood stasis,was a risk factor of UGIB.The risk was higher when prescribing combined with LDA or clopidogrel.Physicians and pharmacists should be aware of risk-benefit profiles when prescribing such medications.We recommend that akafen powder should be given standardized management and classified as a prescription drug for its incredible high risk of UGIB.