| Objective: Coronary heart disease is presently the most prevalentmanifestation of cardiovascular diseases in our country. Non-ST elevationacute coronary syndromes (NSTE-ACS) including unstable angina (UA) andnon-ST elevation myocardial infarction (NSTEMI) are the major presentationof coronary heart disease, and it is well established that NSTE-ACS in theirdifferent clinical presentations share a widely common pathophysiologicsubstrate. In recent years, more and more people have developed toNSTE-ACS, which has had the leading cause of complications and death andimpacted the quality of people’s life. It is known that antiplatelet agents andpercutaneous coronary intervention (PCI) play remarkable roles in improvingprognosis of patients with NSTE-ACS. In this study, we tried to find theoptimal dosage of tirofiban related to double benefits of efficacy and safety inUA and NSTEMI patients undergoing early PCI. We compared clinicalefficacy, bleeding, thrombocytopenia, and major adverse cardiac events(MACE) in different dosages tirofiban groups, in order to provide evidence ofexperience and theory for clinical treatment.Methods：160patients who had been diagnosed as NSTE-ACS in ourdepartment, including80consecutive UA patients and80consecutiveNSTEMI patients, were enrolled into this study from October2010to August2012. All patients underwent coronary angiography (CAG) and PCI within24h after admission.80UA patients were randomized into the UAstandard-dosage group (UA SD group)40patients (average age58.30±9.45years) or UA half-dosage group (UA HD group)40patients (average age56.75±8.28years). Likewise,80NSTEMI patients were randomized into theNSTEMI standard-dosage group (NSTEMI SD group)40patients (average age58.63±9.01years) or NSTEMI half-dosage group (NSTEMI HD group)40patients (average age57.48±8.79years). In both the UA SD group andNSTEMI SD group, tirofiban was administrated a bolus dosage of10μg/kgintravenously within3minutes and followed by continuous intravenousinfusion of0.15μg/kg/min for48hours after PCI immediately. And in boththe UA HD group and NSTEMI HD group, tirofiban was administrated abolus dosage of5μg/kg intravenously within3minutes and followed bycontinuous intravenous infusion of0.075μg/kg/min for48hours after PCIimmediately. The baseline demographics, clinical features, angiographic andprocedural characteristics were observed respectively. Platelet aggregation rate(PAR) was measured before and2h,24h,48h after bolus tirofiban. Bleedingevents were observed at7d after PCI and left ventricular ejection fraction(LVEF) were measured at10d after PCI. The follow-up MACE was evaluatedevery month until180days after PCI. Data analysis was performed by PASW20.0software, and P<0.05was considered statistically significant.Results：1Comparison of baseline demographics and clinical features among thefour groups: No significant differences were found with respect to baselinedemographics and clinical features, such as age, gender, body mass index,smoking history, family history, complications, creatinine clearance rate,alanine transaminase, global registry of acute coronary events (GRACE) scoreand the baseline LVEF (P>0.05).2Comparison of angiographic and procedural characteristics among thefour groups: There was no significant difference among the four groups in PCIvessels, thrombus score, the rate of final thrombolysis in myocardial infarction(TIMI) coronary flow grade3, TIMI myocardial perfusion grading (TMPG)2/3, and the rate of no/slow reflow (P>0.05).3Comparison of LVEF at10days after PCI among the four groups:Compared with half dosage tirofiban, standard dosage tirofiban did notimprove LVEF at10days after PCI significantly (P=0.275) in UA patients.But standard dosage tirofiban improved LVEF at10days after PCI significantly (49.48%vs.44.25%, P=0.000) in NSTEMI patients comparedwith half dosage tirofiban. In this study, we found that the dosage of tirofibanand troponin I (TNI) had interaction trend for improving LVEF, but nostatistical significance was achieved (P=0.077).4Changes of PAR among the four groups: Two hours after bolustirofiban, PAR decreased significantly from baseline and continuouslyremained a relatively low level until48h in four groups. It was found that PARwas lower in SD groups than that in HD groups at2h after bolus tirofiban(P=0.007), but among other time points, no significant difference was found(P>0.05). Repeated measures ANOVA achieved that effect among four groupswas statistical different (P=0.024).5Comparison of bleeding events among the four groups: There was nothrombocytopenia found in all groups. No significant differences were foundwith respect to major bleeding events (P=1.000), and Patients in standarddosage groups had significantly higher rates of minor bleeding events than thatof half dosage groups (P=0.038).6Predictors of bleeding by logistic regression analysis: Multivariatelogistic regression model was tested to explore predictive factors of bleeding.Age, gender, hypertension, diabetes, creatinine clearance rate, PAR<10%(2hafter bolus tirofiban) and tirofiban (standard-dose) were enrolled inmultivariate logistic model. By corrected age, gender, hypertension anddiabetes, the risk of bleeding would increase under the conditions of below:decreased creatinine clearance rate (P=0.000, OR=0.855,95%CI:0.783~0.933),2h after bolus tirofiban PAR<10%(P=0.003, OR=7.616,95%CI:2.021~28.695) and the use of standard dosage tirofiban (P=0.010,OR=7.865,95%CI:1.634~37.862).7Comparison of cumulative MACE among the four groups: At7d, therewas no MACE in four groups. At30d and6month, the incidences of MACEwere not statistically different among four group (P=0.903, P=0.204). Also theLog-rank test did not achieve significant difference (P=0.134).8. Cox proportional hazards regression model analysis of MACE: Age, gender, tirofiban (standard-dose), TNI (positive) and bleeding were enrolled inCox proportional hazards regression model. Age (P=0.033, RR=1.067,95%CI:1.005~1.133) and bleeding (P=0.004, RR=4.497,95%CI:1.610~12.561) wereindependent risks of MACE.Conclusion:1Compared with half dosage tirofiban, standard dosage tirofiban couldsignificantly improve LVEF in the treatment of NSTEMI patients undergoingearly PCI, and in the treatment of UA patients standard dosage tirofiban hadno significant difference. No interaction existed between the dosage oftirofiban and TNI for improving LVEF in this study, but the interaction trendmay be extant.2Two hours after bolus tirofiban, PAR decreased in both standard dosagetirofiban and half dosage tirofiban, and PAR could be lower in standarddosage tirofiban than that in half dosage tirofiban. However, on other timepoints no significant differences existed between standard dosage tirofiban andhalf dosage tirofiban until48hours after bolus dosage.3Half dosage tirofiban was safer in both UA patients and NSTEMIpatients because of fewer bleeding events than standard dosage tirofibanwithin7d after PCI. The risks of bleeding were decreased creatinine clearancerate, increased rate of2h after bolus tirofiban PAR<10%and the use ofstandard dosage tirofiban.4The incidences of cumulative MACE were not statistically different infour groups. Age and bleeding were independent risks of prognosis.5According to results of this study, half dosage tirofiban was not inferiorto standard dosage tirofiban in clinical efficacy of UA patients, what’s more,half dosage tirofiban showed a better safety characteristic of lower bleedingrisk. In NSTEMI patients, standard dosage tirofiban can improve LVEFsignificantly but with higher bleeding risk than half dosage tirofiban. We must balance the benefit between increased LVEF and bleeding risk in NSTEMIpatients undergoing early PCI. |
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