Tirofiban - A review of its use in acute coronary syndromes

被引:86
作者
McClellan, KJ [1 ]
Goa, KL [1 ]
机构
[1] Adis Int Ltd, Auckland 10, New Zealand
关键词
tirofiban; aggrastat; MK-383; pharmacokinetics; pharmacodynamics; therapeutic use; adverse reactions;
D O I
10.2165/00003495-199856060-00017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tirofiban is an intravenously administered nonpeptide glycoprotein IIb/IIIa receptor antagonist which specifically inhibits fibrinogen-dependent platelet aggregation and prolongs bleeding times in patients with acute coronary syndromes. Adenosine diphosphate (ADP)-induced platelet aggregation returns to near-baseline levels within 4 to 8 hours after cessation of a tirofiban infusion, a finding consistent with the drug's elimination half-life of approximate to 2 hours, Three large clinical trials have shown that, when administered with a standard heparin and aspirin regimen, tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction (MI) and in patients undergoing percutaneous revascularisation. In PRISM-PLUS, a study involving 1915 patients with unstable angina/non-Q-wave MI, administration of intravenous tirofiban (0.4 mu g/kg/min loading dose for 30 minutes followed by a 0.10 mu g/kg/min infusion) with heparin for at least 38 (mean 71.3) hours reduced the 7-day risk of the composite end-point of MI, death and refractory ischaemia by 32% compared with heparin alone, The between-group risk reduction remained significant at 30 days (22%) and 6 months (19%). Similarly, in high-risk patients undergoing coronary angioplasty in RESTORE, the addition of tirofiban (10 mu g/kg bolus in the 3 minutes prior to intervention followed by 0.15 mu g/kg/min for 36 hours) to a standard heparin regimen significantly reduced the risk of ischaemic complications by 38% on day 2 and 27% on day 7 compared with heparin alone, Although interim analysis in PRISM-PLUS showed that the use of tirofiban without heparin increased the 7-day risk of death compared with heparin alone, this finding was inconsistent with the effects of tirofiban on the risk of death in PRISM, a study involving 3232 patients with unstable angina/non-Q-wave MI. Tirofiban is generally well tolerated. Bleeding complications were the most commonly reported events associated with tirofiban in clinical trials, but the rate of major bleeding in tirofiban recipients was not significantly different from that reported with heparin, Thrombocytopenia (platelet count <90 000 cells/mu l) occurred slightly more frequently with tirofiban (with or without heparin) than with heparin alone, Conclusions: Tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave MI and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin, Furthermore, the drug has an acceptable tolerability profile, Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.
引用
收藏
页码:1067 / 1080
页数:14
相关论文
共 29 条
[1]   PHARMACOKINETICS AND PHARMACODYNAMICS OF MK-383, A SELECTIVE NONPEPTIDE PLATELET GLYCOPROTEIN-IIB/IIIA RECEPTOR ANTAGONIST, IN HEALTHY-MEN [J].
BARRETT, JS ;
MURPHY, G ;
PEERLINCK, K ;
LEPELEIRE, ID ;
GOULD, RJ ;
PANEBIANCO, D ;
HAND, E ;
DECKMYN, H ;
VERMYLEN, J ;
ARNOUT, J .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 56 (04) :377-388
[2]  
Bazzino O, 1998, NEW ENGL J MED, V338, P1498
[3]  
Bazzino O, 1998, NEW ENGL J MED, V338, P1488
[4]   USE OF A MONOCLONAL-ANTIBODY DIRECTED AGAINST THE PLATELET GLYCOPROTEIN IIB/IIIA RECEPTOR IN HIGH-RISK CORONARY ANGIOPLASTY [J].
CALIFF, RM ;
SHADOFF, N ;
VALETT, N ;
BATES, E ;
GALEANA, A ;
KNOPF, W ;
SHAFTEL, J ;
BENDER, MJ ;
AVERSANO, T ;
RAQUENO, J ;
GURBEL, P ;
COWFER, J ;
COHEN, M ;
CROSS, P ;
BITTL, J ;
EDDINGS, K ;
TAYLOR, M ;
DEROSA, K ;
HATTEL, L ;
COOPER, L ;
ESHELMAN, B ;
FINTEL, D ;
NIEMYSKI, P ;
KLEIN, L ;
KENNEDY, H ;
THORNTON, T ;
KEREIAKES, D ;
MARTIN, L ;
ANDERSON, L ;
HIGBY, N ;
ELLIS, S ;
BREZINA, K ;
GEORGE, B ;
CHAPEKIS, A ;
SMITH, D ;
ANWAR, A ;
GERBER, TL ;
PRITCHARD, GL ;
MYLER, R ;
SHAW, R ;
MURPHY, M ;
WARD, K ;
MADIGAN, NP ;
BLANKENSHIP, J ;
HALBERT, M ;
FLANAGAN, C ;
TANNENBAUM, M ;
POLICH, M ;
STEVENSON, C ;
TCHENG, J .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (14) :956-961
[5]   New antiplatelet agents for acute coronary syndromes [J].
Ferguson, JJ ;
Lau, TK .
AMERICAN HEART JOURNAL, 1998, 135 (05) :S194-S200
[6]  
FUSTER V, 1992, NEW ENGL J MED, V326, P310
[7]   A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) [J].
Gent, M ;
Beaumont, D ;
Blanchard, J ;
Bousser, MG ;
Coffman, J ;
Easton, JD ;
Hampton, JR ;
Harker, LA ;
Janzon, L ;
Kusmierek, JJE ;
Panak, E ;
Roberts, RS ;
Shannon, JS ;
Sicurella, J ;
Tognoni, G ;
Topol, EJ ;
Verstraete, M ;
Warlow, C .
LANCET, 1996, 348 (9038) :1329-1339
[8]   Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial [J].
Gibson, CM ;
Goel, M ;
Cohen, DJ ;
Piana, RN ;
Deckelbaum, LI ;
Harris, KE ;
King, SB .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1998, 32 (01) :28-34
[9]   DETERMINATION OF MK-383, A NONPEPTIDE FIBRINOGEN RECEPTOR ANTAGONIST, IN HUMAN PLASMA AND URINE BY RADIOIMMUNOASSAY [J].
HAND, EL ;
GILBERT, JD ;
YUAN, AS ;
OLAH, TV ;
HICHENS, M .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 1994, 12 (08) :1047-1053
[10]  
Hanrath P, 1997, CIRCULATION, V96, P1445