| Objective:In this paper, through the analysis of patients first diagnosiswith pulmonary embolism, we explored the influential factors on warfarin’sfirst standard time to therapeutic range.Methods:Patients firstly diagnosis with pulmonary embolism, from2008to2013June were collected in this study. We gathered their demographic data,tobacco and alcohol intake, diseases,liver and kidney function test, bloodtest,warfarin adjustments and motoring INR in hospital, concomitant drugsapplication before the standard.Based on the first standard time to therapeuticrange (INR was in the therapeutic range2.0-3.0for at least two days continu-ously), Different first standard time to therapeutic range divided into fourgroups:Group I:t≤7d、Group II:7d<t≤14d、Group III:14d<t≤28d、Group IV:t>28d, Call patients for follow-up involved with the following questions:hemorrhage (serious bleeding, mild bleeding) or embolism within90days oftaking warfarin, and prognosis (better, cure,inefficient).Results:1Statistical analysis of single factor1.1Initial doseIn302patients,most of them took three kinds of dose:2.5mg,3mg,5mg,The first standard time of2.5mg,3mg,5mg were concentrated on14~28days(44.14%),7～28days(60.25%),1～7days (41.67%), these difference wasstatistically significant (P=0.001).1.2Analysis of demographic data1.2.1Sex and AgeIn302patients, the average age of four different standard timerespectively were57.76±15.68years old,6.18±13.37years old,56.56±14.64years old,57.22±13.15years old, the difference was not statistically significant (P=0.913); The first standard time of men and women respectivelywere concentrated on14~28days, the proportions respectively were38.46%,33.72%, the difference was not statistically significant (P=0.287).Sex,age didnot influence on the first standard time.1.2.2BMIIn302patients, the average of BMI was18.5~23.9kg/m2.normal BMI, Idegree of obesity,II degree of obesity were respectively concentrated on1~7days(36.59%),14~28days(43.9%),>28days(33.33%).the proportion of overwe-ight in four different standard time are equal.The difference was statisticallysignificant (P <0.001).BMI affected the first standard time.1.3Disease, smoking, alcohol intake history1.3.1Smoking, alcohol intake historyIn302patients,The first standard time of patients with alcohol intake andnon-alcohol intake was mainly concentrated on<28days, the proportion wererespectively84.51%,88.89%, The difference was statistically significant (P=0.316); Smokers’ standard time was mainly concentrated on1~7days (35.29%)and15~28days (35.04%),non-smokers’ standard time was concentrated on8~28day (64.95%), The difference was statistically significant (P=0.107);Smoking,alcohol intake did not affect on the first standard time.1.3.2DiseasesIn302patients,71.43%of patients with heart failure, whose the firststandard time was less than14days,64.24%of patients without heart failurewhose the first standard time was more than14days, the difference wasstatistically significant (P<0.001). And hypertension (including blood pressurecontrol stability and instability), diabetes mellitus, malignancy,the differenceswere not statistically significant.Heart failure affected the first standard time.1.4Clinical laboratory DataThe first standard time of patients with Hepatic insufficiency beforetreatment was mainly concentrated on1~7days (36.36%) and15~28days(40.91%), The first standard time of patients with normal liver functionwas8～28days (62.79%),the difference was statistically significant (P=0.019). The first standard time of patients with normal serum albumin wasconcentrated on14~28days(34.88%), ALB slight drop group was moreevenly distributed, the difference was not statistically significance (P=0.754).Ccr stood for glomerular filtration rate(GRF),The proportion of normalrenal function, slight drop group,moderate drop group in four differentstandard time were respectively concentrated on14~28days(43.84%),7~14days(30%)14~28days (40.91%),the difference was not statistically significant(P=0.224).The proportion of patients without anemia, mild anemia, moderate anem-ia in four different standard time were concentrate on<28days(86.78%),>14days (71.43%),≤14days(77.77%),the difference was not statisticallysignificant(P>0.05). So Live function only affected the first standard time.1.5Drugs1.5.1Antibacterial drugs66.66%of non-cephalosporins group’s first standard time were concen-trated on7~28days, while the application group were concentrated on≤7days(30.25%) and14~28days(36.79%),the difference was statistically significant(P<0.05).The proportion of patients with Levofloxacin group or non-Levofloxacin in four different standard time were concentrated on≤7days(45.83%),14~28days(39.37%), the difference was statistically significant (P<0.05). Cephalosporin,Levofloxacin affected the first standard time.Broad-spectrum antibiotics penicillins (ampicillin,mezlocillin sulbactam,amoxicillin,azlocillin flucloxacillin,piperacillin sulbactam,), Antifungal agent(voricona-zole, caspofungin, fluorine itraconazole), their P were>0.05, the differencewas not statistically significant.1.5.2Cardiovascular drugsCalcium channel blockers(Nifedipine),β-blocker high selectivity(metor-prolol, bisoprolol), Diuretics(furosemide, spironolactone),ACEI drugs, lipid-lowering drugs statins (fluvastatin,simvastatin,atorvastatin), Aspirin, their Pvalue were>0.05, the difference was not statistically significant.1.5.3Other drugs Most drugs of Huo xue hua yu application,non-application’s time were<28days,the proportion were respectively91.76%、74.99%,the difference wasstatistically significant (P=0.001). Proton pump inhibitors (esomeprazole,omeprazole), adrenal cortical hormones, their P were>0.05,the differencewas not statistically significant.2Ordered multivariate logistic regression analysis2.1Compared with5mg,the initial dose of2.5mg and3mg group preferred toprolong the standard time.(OR>1, P <0.05)2.2Compared with II degree of obesity group, overweight and normal BMIgroup can shorten the time of reaching the therapeutic range.(OR<1,P<0.05)The difference of prolonging the standard time between II degree of obesitygroup and I degree of obesity group were not statistical significance.(OR=2.08,P=0.269)2.3Hepatic insufficiency group preferred to shorten the first standard timethan normal liver function.(OR=0.011,P=0.006)2.4Heart failure group preferred to shorten the first standard time thannon-heart failure group.(OR=0.025, P=0.002)2.5Non-application of levofloxacin group, preferred to prolong the firststandard time.(OR=1.375,P<0.05)2.6The cephalosporin and drugs of Huo xue Hua yu weren’t independentinfluential factors of the first standard time.(OR>1, P>0.05)3Anti-coagulation effect and adverse reaction3.1Anti-coagulation effectAfter taking warfarin for90days,CTPA showed pulmonary arterythrombosis disappeared and no obvious symptoms,were named of cure(n=71,23.4%).CTPA showed pulmonary thromboembolism area decrease or theclinical symptoms were improved, were named of improvement(n=231,76.6%)no cases were inefficacy.3.2Adverse reactionsAdverse reactions included hemorrhage and embolism, bleeding weredivided into mild and severe bleeding.The number of minor bleeding was72 (23.84%), The number of severe bleeding was10(3.31%), Five patientsoccured embolism, the proportion was only1.54%.4Relation between INR>4before the standard and factors4.1Normal BMI, overweight, I and II degree of obesity’s INR>4.0ratiobefore reaching the standard were7.32%,8.89%,4.88%,4.17%, the differe-nce had no statistical significance(P>0.05);4.2The initial dose of2.5mg,3mg,5mg groups’ INR>4ratio before reachingthe standard were14.53%,18.06,23.33%,the difference had no statisticalsignificance(P>0.05);4.3Hepatic insufficiency and the normal groups’ INR>4ratio before reachingthe standard were11.54%,4.91%,the difference was statistically significance.4.4Application of levofloxacin, non-levofloxacin groups’ INR>4ratio were12.20%,4.55%, the difference was statistical significance (P=0.017).8.65%of Huo xue Hua yu drugs and7.56%of cephalosporin application had theoccurrence of INR>4.0before reaching the standard, All of them had higherincidence than non-application groups, but no statistically significant.5Statistical analysis of single factor about maintenance dose5.1Demographic dataIn302patients, The average maintenance dose of male, female were3.50±1.33mg,3.28±1.30mg, the difference was not statistically significance(P=0.107);The average maintenance dose of youth groups (age <40), middleage group (age41~65years old), the old group (aged>65years) were3.76±1.86mg,3.56±1.22mg,3.05±1.43mg,Along with the increase of age, themaintenance dose would be decreased, the difference was statisticallysignificant (P=0.004); The average maintenance dose of normal BMI group,overweight, I degree of obese group, II degree of obesity group were3.24±1.43mg,3.26±1.27mg,3.42±1.13mg,3.50±1.33mg, Along with theincrease of BMI index, the maintenance dose would be increased, and thedifference was statistically significant (P=0.013).The results showed that age,BMI were influential factors of maintenance dose, but gender had no influenceon it. 5.2Diseases, smoking and alcohol intakeIn302patients, The average maintenance dose of smokers, non-smokerswere3.50±1.32mg,3.20±1.30mg, no significant difference (P=0.063); Theaverage maintenance dose of alcohol intake group, non-alcohol intake groupwere3.42±1.33mg,3.15±1.09mg, no significant difference (P=0.463). Theresults showed that smoking, alcohol intake had no effect on maintenancedose.In302patients, the average maintenance dose of heart failure group, nonheart failure group were2.81±1.42mg,3.50±1.27mg, the maintenance doseof heart failure group was lower than the other. the difference was statisticallysignificant (P=0.003); the results showed heart failure was an influential factorof maintenance dose, but hypertension (including blood pressure controlstability and unstable), diabetes mellitus, malignant tumor had no effect on themaintenance dose.5.3Clinical laboratory dataIn302patients, the average maintenance dose of liver dysfunction groupbefore treatment, normal liver function were2.87±1.47mg,3.55±1.24mg,the maintenance dose of liver dysfunction group was relatively lower, thedifference was statistically significant (P=0.001); Liver function was aninfluential factor of maintenance dose, but ALB, renal function, anemia had noeffect on the maintenance dose.5.4DrugsIn302patients’ concomitant drugs: Cephalosporins, penicillins, levoflo-xacin had no effect on the maintenance dose.Calcium channel blockers(Nifedipine),β-blocker high selectivity(metor-prolol, bisoprolol), Diuretics(furosemide, spironolactone),ACEI drugs,lipid-lowering drugs statins (fluvastatin,simvastatin,atorvastatin), Aspirin,their P value were>0.05, the difference was not statistically significant.theresults showed cardiovascular drugs had no effect on the maintenance dose.In302patients, drugs of huo xue hua yu, proton pump inhibitors, adrenalcortical hormone,whose P value were more than0.05, the difference was not statistically significant, the results showed that the three drugs had no effect onthe maintenance doseThrough single factor analysis, age, BMI, heart failure, liver functionwere influential factors of warfarin maintenance dose.6Multivariate linear regression analysis of maintenance doseAge, BMI, liver function, heart failure were expressed by X1, X2, X3, X4,maintenance dose was expressed by Y. X1, X2, X3, X4brought into multiplelinear regression analysis:6.1Age’s partial regression coefficient B=-0.001, this showed that age had anegative correlation with maintenance dose. Along with age increased, themaintenance dose woulid be reduced.6.2BMI’s B=0.063, this showed that BMI had a positive correlation withmaintenance dose. Along with BMI increased, the maintenance dose woulidbe more.6.3B of liver function was-0.257, the liver function had a negative correlationwith maintenance dose. When liver insufficiency existed, the maintenancedose would be reduced.6.4B of heart failure was-0.043, heart failure had a negative correlation withmaintenance dose. When heart failure existed, the dose would be decreased.6.5Age, BMI, liver function, heart failure were influential factors of warfarinmaintenance dose.6.6Effect coefficient Beta of these four factors were respectively-0.015,0.187,-0.155,-0.023, the influential strength of the above factors on mainte-nance doses from strong to weak were: BMI, liver function, heart failure, age.6.6The multivariate linear regression analysis obtained the calculationformulaY (mg)=2.574-0.001X1+0.063X2-0.257X3-0.043X4Conclusion:1Results of single factor analysis: the initial dose, BMI, liver function,heart failure, levofloxacin, cephalosporins, drugs of Huo xue Hua yu affectedthe first standard time.2Results of ordered multivariate Logistic regression analysis: the initial dose, BMI, liver function, heart failure, levofloxacin were Influential factorsfor the first standard time.3The influential factors on the ratio of INR>4before the standard wereheaptic insufficiency, application of levofloxacin.4Results of single factor analysis about maintenance dose: age, BMI,live fuction, heart failure were Influential factors of maintenance dose.5The multivariate linear regression analysis showed that age (X1), liverfunction (X3), heart failure (X4) had the negative correlation withmaintenance dose, while BMI (X2) the positive correlation with maintenancedose.maintenance dose’s calculation formula:Y(mg)=2.574-0.001X1+0.063X2-0.257X3-0.043X4... |
PDF Full Text Request