Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2016; 20: 1356-1359 Clinical effects of treatment with Tirofiban on patients with high-risk NSTE-ACS after PCI

P. WEI 1, Y.-J. HUANG 1, X.-H. Z UO 2, Y.-G. ZHANG 1, Z.-Q. TAO 3, C.-R. QIU 1, Q. ZHANG 1, X.-J. YANG 4, Q. FU 1

1Department of Cardiology, Central Hospital, Xuzhou, 2Department of Cardiology, First People’s Hospital, Jinan, China 3Department of Science and Education, Xuzhou Central Hospital, Xuzhou, China 4Department of Cardiology, First Affiliated Hospital, Soochow University, , China Peng Wei, Yi-jie Huang, Xi-hong Zuo, Yi-gang Zhang and Zi-qi Tao contributed equally to this work

Abstract. – OBJECTIVE: To explore clinical complications and high mortality is due to rup - effects of Tirofiban treatment on patients with high-risk non-ST-segment elevation acute coro - ture of unstable atherosclerotic plaque in the nary syndrome (NSTE-ACS) after percutaneous coronary artery, which leads to the formation of coronary intervention (PCI). incomplete obstructive thrombus and, therefore , PATIENTS AND METHODS: 107 patients with acute cardiac ischemia syndrome. Since platelet high-risk NSTE-ACS after PCI were selected and aggregation is an important consequence and ini - were divided into two groups. One group of 56 tiative factor of the formation of thrombus, an - patients was treated with Tirofiban and a second tiplatelet therapy has of particular importance. group of 51 patients was taken as control. The occurrence conditions of creatine kinase-myo - Therefore, we discussed the impact of enhanced globin (CK-MB), cardiac troponin1 (cTnI) level, antithrombotic therapy on patients with high-risk hemorrhage incidents and major adverse car - NSTE-ACS treated by Tirofiban after emergent diac events (MACE) incidents after treatments percutaneous coronary intervention (PCI) . were compared. RESULTS: After 24 h operation, CK-MB and cT - nI level in Tirofiban group were both significant - ly lower than those in control group ( p < 0.05), Patients and Methods while the difference of hemorrhage incidents be - tween two groups is of no statistical signifi - Patients cance ( p < 0.05); and the differences in overall The study was conducted on 107 patients with occurrence rate of MACE incidents and the oc - high-risk NSTE-ACS admitted in Xuzhou Cen - currence rate of angina pectoris after infarct be - tral Hospital between January 2013 and January tween two groups were statistically significant 2015. The study was started since from the ap - (p < 0.05). CONCLUSIONS: Tirofiban could improve the pearance of the first symptom. There were 61 blood supply condition of hearts of patients with were male patients and 46 were female patients high-risk NSTE-ACS after emergent PCI, lower of age range between 35 to 75 years , and with an the occurrence rate of MACE incidents, and de - average age of 58.13 ± 14.70 years. All patients crease the risk of hemorrhage. selected were confirmed to the diagnosis by the standard of high-risk patients GRACE score > Key Words: ACS, NSTE, Tirofiban, PCI, MACE incidents . 140 in NSTE-ACS diagnosis instruction which was formulated by Chinese Society of Cardiolo - gy of Chinese Medical Association in 2012 . The following patients were excluded: (1) Pa - tients having the history of myocardial infarction Introduction disease, PCI and coronary artery bypass grafting; (2) Patients with chronic cardiac failure and liver Non-ST -segment elevation acute coronary and kidney function deficiency; (3) Allergic to syndromes (NSTE-ACS) includes unstable angi - aspirin, h eparin, Tirofiban and contrast agent; (4) na pectoris (UA) and non-ST segment elevation Unmanageable hypertension; (5) Patients having myocardial infarction (NSTEMI). The cause of active hemorrhage and hematological system dis -

1356 Corresponding Author: Qiang Fu, MD; e-mail: [email protected] Clinical effects of treatment with Tirofiban on patients with high-risk NSTE-ACS after PCI eases within three months before being selected; Definitions of Hemorrhage and (6) Patients having cerebrovascular disease and MACE Incidents peripheral vascular disease. (1) Hemorrhage Incidents: Hemoglobin de - There were 56 patients in Tirofiban group and clined more than 50 g/L or red blood cell hemat - 51 patients in control group according to whether ocrit declined more than 15% caused by intracra - they were treated by Tirofiban or not, and there nial hemorrhage and alimentary tract hemorrhage were matched for gender, age, BMI, history of were considered as massive hemorrhage; while smoking, history of alcohol intake, history of hy - hemoglobin declined more than 30 g/L or red pertension, history of diabetes mellitus and the blood cell hematocrit declined more than 10% intakes of nitrate lipid, b-BRB, ACEI/ARB and caused by spontaneous hematuria and hemateme - statins ( p > 0.05). sis were considered as slight hemorrhage. Blood loss did not reach the criteria above was consid - Therapeutic Methods ered as non-obvious hemorrhage. (2) MACE In - PCI operations were performed on patients in cidents: The occurrence conditions of cardiac in - both groups within 24 h from the appearance of cidents such as secondary heart failure, severe ar - symptoms. 300 mg aspirin for chewing and 300 rhythmia (ventricular tachycardia, ventricular mg clopidogrel for oral intake were given before fibrillation and atrioventricular block of level II, the operation. Coronary angiography was done level III or above), post-infarction angina pec - through the right radial artery or femoral artery toris, recurrence of myocardial infarction, car - puncture path to determine the number of dis - diac death and so on of patients were recorded eased coronary arteries and culprit’s vessels, af - within 6 months since showing symptoms (in - ter which PCI was given. After the operation, it cluding the period of hospitalization ). was shown by coronary angiogram that all resid - ual stenosis were lower than 20%, and level 3 Statistical Analysis thrombolysis in myocardial infarction (TIMI ) SPSS 19.0 software (SPSS Inc., Chicago, IL, blood flow appeared (operation successfully USA) was adopted, and the measured data were completed). All patients were normally treated represented by mean ± standard deviation. The with aspirin, clopidogrel and enoxaparin sodium, independent sample t-test was adopted for com - and patients with indications were treated by b- parison between groups; rates were represented BRB , nitrate lipid and ACEI/ARB simultaneous - by percentages, and c2-test or Fisher exact test ly. Intravenous bolus injection was used to inject was adopted for comparison between groups. p < 10 µg/kg Tirofiban to patients in Tirofiban 0.05 means the difference was of statistical sig - group, and the injection period was no less than 3 nificance. min, after which Tirofiban was continuously in - jected by intravenous route for 36 h at the rate of 0.15 µg/kg /min. Results

Detections of the Levels of CK-MB Comparison of CK-MB and cTnI Levels and cTnI Between Two Groups 7600-020 automatic biochemical analyzer The differences of CK-MB and cTnI levels be - (produced by Hitachi Corporation, Tokyo, Japan) tween two groups at the time of admission to and its corresponding kits (produced by hospital are of no statistical significance ( p < Fosun Long March Medical Science Co. Ltd, 0.05 ); while 24 hrs after the operation, CK-MB China) were adopted to detect the levels of CK- and cTnI levels of Tirofiban group are both sig - MB of patients at the time of admission and was nificantly lower than those of control group ( p < repeated after 24 hours of operations by the 0.05) ( Table I). method of immunosuppression, and Centaur CP chemiluminescence apparatus (produced by Comparison of Occurrence Conditions Siemens Corporation, Munich, Germany). The of Hemorrhage Incidents Between corresponding kits (produced by Siemens Corpo - Two Groups ration, Munich, Germany) were adopted to detect There was one case of massive hemorrhage the levels of cTnI of patients at the time of ad - (1.8%), one case of slight hemorrhage (1.8%) mission and 24 hours after operations by the and one case of non-obvious hemorrhage (1.8%) method of chemiluminescence. in the Tirofiban group . There were no cases of

1357 P. Wei, Y.-J. Huang, X.-H. Zuo, Y.-G. Zhang, Z.-Q. Tao, C.-R. Qiu, Q. Zhang, X.-J. Yang, Q. Fu

Table I. Comparison of CK-MB and cTnI levels.

Groups n CK-MB (u/L) cTnI (ng/ml)

Tirofiban group 56 Before treatment 50.78 ± 9.62 1.25 ± 0.65 After treatment 216.88 ± 35.26* 4.18 ± 1.03* Control group 51 Before treatment 50.71 ± 10.10 1.40 ± 0.61 After treatment 244.64 ± 18.83 4.71 ± 1.08

Note : Compared with control group after treatment, * p < 0.05.

massive hemorrhage (0%), one case of slight he - used anti-thrombotic drugs clinically include as - morrhage (1.9%) and one case of non-obvious pirin, clopidogrel, and heparins. By the inhibition hemorrhage (1.9%) in the control group. The dif - of epoxidase, aspirin could inhibit the synthesis ference of occurrence rates of overall hemor - of blood platelet thromboxane A2 (TXA2 ) and rhage incidents between the two groups is of no release or reduce the platelet aggregation. Clopi - statistical significance ( p > 0.05). dogrel could block platelet aggregation through ADP pathway, and both of them are invalid for Comparison of Occurrence Conditions of platelet aggregation induced by other activators. MACE Incidents between Two Groups However, the common pathway of inducing The difference of overall occurrence rates of platelet aggregation is GPIIb/IIIa receptor on the MACE incidents between two groups was of sta - surface of blood platelet, thus blocking its func - tistical significance ( p < 0.05), among which the tion is sure to eliminate platelet aggregation in - difference in the occurrence rate of post-infarc - duced by activators. tion angina pectoris between the two groups was Tirofiban belongs to non-peptide blood of statistical significance ( p < 0.05) (Table II). platelet glycoprotein IIb/IIIa (GPIIb/IIIa ) recep - tor antagonist, which has high degree of speci - ficity and can block the conjunction of fibrino - Discussion gen and receptor and, therefore, inhibit the final pathway of platelet aggregation, which competi - In recent years, the occurrence rate of acute tively inhibit platelet crosslinking and aggrega - coronary syndrome (ACS ) is increasing year by tion caused by various reasons including adrena - year for patients with NSTE-ACS, and especially line, 5-hydroxytryptamine, adenosine 5’-diphos - for those high-risk patients NSTE-ACS would phate (ADP ), collagen, thrombin , etc. The addi - develop into STE-ACS or even sudden cardiac tion of Tirofiban to the conventional anti-platelet death without treatment in a timely and effective drug treatments can provide more powerful, manner 1,2,9 . Currently, PCI operation is consid - comprehensive and thorough anti-thrombotic ef - ered as the primary method for high-risk NSTE- fects, which are beneficial for cardiac blood sup - ACS myocardial reperfusion therapy, and at the ply and cardiac function [3] . We showed that 24 h same time anti-thrombotic drugs enhancement after PCI operation, CK-MB and cTnI levels in has become particularly important. The regularly the Tirofiban group were both significantly lower

Table II. Comparison of occurrence conditions of MACE incidents [cases (%)].

Recurrence Secondary Severe Post-infarction of myocardial Cardiac Groups N heart failure arrhythmia angina pectoris infarction death

Tirofiban group 55 2 (3.6%) 4 (7.3%) 1 (1.8%)* 1 (1.8%) 1 (1.9%) Control group 52 4 (7.7%) 6 (11.5%) 8 (15.4%) 3 (5.8%) 2 (3.8%) c2 0.241 0.181 4.746 0.321 0.000 p 0.623 0.671 0.029 0.571 0.987

1358 Clinical effects of treatment with Tirofiban on patients with high-risk NSTE-ACS after PCI than those in the control group, which directly 2) LEI D, W ANG J, W ANG Y. The impacts of Tirofiban demonstrates the anti-thrombotic treatment ef - on coronary no reflow of young patients with fects of Tirofiban. acute ST segment elevation myocardial infarction after PCI operation. Med J 2014; 54: The studies have shown by using Tirofiban as 73-74. the basis of aspirin, clopidogrel and heparin 3) MANGIACAPRA F, M ULLER O, N TALIANIS A, T RANA C, treatments for the treatment of high-risk ACS pa - HEYNDRICKX GR, B ARTUNEK J, V ANDERHEYDEN M, W IJNS tients. The patients have received emergent PCI W, D E BRUYNE B, B ARBATO E. Comparison of 600 treatment has better clinical effects, but there versus 300-mg Clopidogrel loading dose in pa - were some adverse reactions such as hemorrhage tients with ST-segment elevation myocardial in - [4,5] farction undergoing primary coronary angioplasty. and thrombocytopenia . The results of this re - Am J Cardiol 2010; 106: 1208-1211. search showed that patients in Tirofiban group 4) YANG F, L AI S, W ANG H. The effects of home-pro - have no obvious increase in terms of overall he - duced Tirofiban on myocardial microcirculation morrhage incidents. In the recent years, it has reperfusion after coronary artery intervention. been also shown that GPIIB/IIIA receptor antag - Chinese Journal of Cardiovascular Rehabilitation onists (Tirofiban) can significantly reduce the oc - Medicine, 2008; 17: 365-368. currence rate and morbidity rate of myocardial 5) GIBSON CM, D OTANI MI, M URPHY SA, M ARBLE SJ, infarction in patients with acute coronary syn - DAUTERMAN KW, M ICHAELS AD, D ODGE JT J R; RE - 6-10 STORE I NVESTIGATORS . Correlates of coronary blood drome . The two groups have no significant flow before and after percutaneous coronary in - differences in cardiac incidents such as sec - tervention and their relationship to angiographic ondary heart failure, severe arrhythmia, recur - and clinical outcomes in the RESTORE trial. Ran - rence of myocardial infarction and cardiac death, domized Efficacy Study of Tirofiban for Outcomes while occurrence rates of post-infarction angina and REstenosis. Am Heart J 2002; 144: 130-135. pectoris and overall MACE incidents in 6) SCHNEIDER DJ, H ERRMANN HC, L AKKIS N, A GUIRRE F, L O MW, Y IN KC, A GGARWAL A, K ABBANI SS . Increased Tirofiban group were significantly lower. concentrations of Tirofiban in blood and their cor - relation with inhibition of platelet aggregation after greater bolus doses of Tirofiban. Am J Cardiol Conclusions 2003; 91: 334-336. 7) Y. Evaluation on the safety and efficacy of Tirofiban improves cardiac blood supply, low - Tirofiban in the treatment of acute coronary syn - ers the levels of myocardial enzymes and tro - drome. J Huazhong Univ Sci Technol Med Sci 2007; 27: 142-144. ponin and occurrence rate of MACE incidents in 8) SUN Z, Z ENG J, H UANG H. Intracoronary injection of enhanced anti-thrombotic treatments of patients tirofiban prevents microcirculation dysfunction with high-risk NSTE-ACS after emergent PCI during delayed percutaneous coronary interven - operation, and also reduces the risk of hemor - tion in patients with acute myocardial infarction. rhage. Int J Cardiol 2016; 208: 137-140. 9) MA CP, W ANG X, W ANG QS, L IU XL, H E XN, N IE SP . –––––––––––––––– –-– –– A modified HEART risk score in chest pain pa - Conflict of Interest tients with suspected non-ST-segment elevation acute coronary syndrome. J Geriatr Cardiol 2016; The Authors declare that there are no conflicts of interest. 13: 64-69. 10) KIM JS, H AN DC, J EONG YH, P ARK DW, S OHN CB, HWANG KW, L EE SH, C HOI JH, C HON MK, L EE SY, References HWANG J, K IM IS, L EE SM, H AN J, N OH M, K IM CH, CHUN KJ, P ARK YH, K IM JH . Antiplatelet effect of 1) FUSTER V, B ADIMON L, B ADIMON JJ, C HESEBRO JH . The ticagrelor compared to tirofiban in non-ST- pathogenesis of coronary artery disease and the segment elevation ACS patients undergoing PCI. acute coronary syndromes. N Engl J Med 1992; The result of the TE-CLOT trial. Thromb Haemost 326: 242-250. 2015; 115: 213-221.

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