Randomised Trial of Intravenous Recombinant Tissue-Type Plasminogen Activator Versus Intravenous Streptokinase in Acute Myocardial Infarction

Verstraete, Marc; Bory, M; Collen, D.; Erbel, Raimund; Lennane, R. J.; Mathey, D; Michels, H. R.; Schartl, M.; Uebis, R.; Bernard, R; Brower, R. W.; Bono, David P. de; Huhmann, W; Lubsen, Jacobus; Meyer, Jürgen; Rutsch, Wolfgang; Schmidt, Wolfgang G.; Essen, R. von

doi:10.1016/s0140-6736(85)92208-1

Cited by 721 publications

(107 citation statements)

References 23 publications

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“…However, the events leading to such attack can be alleviated by suitable thrombolytic treatment with tissue plasminogen activator, urokinase, or streptokinase. Unfortunately these often induce acute thrombotic reocclusion (Chesebro et al, 1987;Verstraete et al, 1985;While et al, 1989;Wilcox et al, 1988). Although the mechanism of reocclusion is not known, the possible role of thrombus-bound thrombin, which is still active, has been proposed (Francis et al, 1983;Agnelli et al, 1991), indicating the need for potent and specific pharmacological agents.…”

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confidence: 99%

Design of Potent Bivalent Thrombin Inhibitors Based on Hirudin Sequence: Incorporation of Nonsubstrate-Type Active Site Inhibitors

Tsuda¹,

Cygler²,

Gibbs³

et al. 1994

Biochemistry

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Hirudin from medicinal leech is the most potent and specific thrombin inhibitor from medicinal leech with a K, value of 2.2 x M. It consists of an active site blocking moiety, hirudin'-48, a fibrinogen-recognition exo-site binding moiety, hir~din~~-~~, and a linker, hir~din~~-~~, connecting these inhibitor moieties. Synthetic inhibitors were designed based on the C-terminal portion of hirudin. The bulky active site blocking moiety, was replaced by small nonsubstrate-type active site inhibitors of thrombin, e.g., dansyl-Arg-(D-pipecolic acid). The linker moiety was replaced by o-amino acids of (12-aminododecanoic acid)-(4-aminobutyric acid), and hirudi~P-~~ was used as a fibrinogen-recognition exo-site binding moiety in most of the inhibitors. The crystal structure of the inhibitor in complex with human a-thrombin showed that dansyl, Arg, and D-pipecolic acid of the active site blocking moiety occupy S3, S1, and S2 subsites of thrombin, respectively, and were therefore designated as P3, P1, and P2 residues.The use of dansyl-Arg-(D-pipecolic acid) improved the affinity (KJ of the inhibitor 10-100-fold (down to 1.70 x lo-" M) compared to that of the similar compounds having D-Phe-Pro-Arg as their substratetype inhibitor moiety (K = 10-9-10-10 M). The linker connected to P2 residue eliminated the scissile peptide bond. The inhibitor was also stable against human plasma proteases. Further inhibitor design revealed that the toxic dansyl group could be replaced by 4-tert-butylbenzenesulfonyl group and 1-or 2-naphthalenesulfonyl group for in vivo studies. In addition, the replacement of hir~din~~-~~ with [TY~~~,-

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mentioning

confidence: 99%

Design of Potent Bivalent Thrombin Inhibitors Based on Hirudin Sequence: Incorporation of Nonsubstrate-Type Active Site Inhibitors

Tsuda¹,

Cygler²,

Gibbs³

et al. 1994

Biochemistry

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“…The results of different multicenter studies are available3-7 and there is general agreement that the rate of successful thrombolysis is higher with rt-PA than LABORATORY INVESTIGATION-CORONARY THROMBOLYSIS with intravenous streptokinase when the former is administered 4 to 5 hr after symptom onset and that reperfusion is accomplished with much less pronounced systemic fibrinogen depletion.3-7 However, a major problem has emerged from these initial trials; that is, despite a reperfusion frequency between 61% and 85%, acute coronary reocclusion developed in 20% to 45% of these patients, even when patients were fully heparinized. [3][4][5][6][7] Recently, a prolonged maintenance infusion of rt-PA has been shown to decrease the frequency of coronary reocclusion,8 but this problem is still far from being solved.…”

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confidence: 99%

Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis.

et al. 1988

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Human recombinant tissue-type plasminogen activator (rt-PA) has been shown to be an effective and safe agent for coronary thrombolysis in patients with acute myocardial infarction. However, thrombolysis is associated with a high rate of acute reocclusion after discontinuation of rt-PA. The goals of the present study were to assess whether reocclusion after thrombolysis is caused by intracoronary platelet aggregation and to determine the role of thromboxane A2 (TxA2) No. 3, 678-684, 1988. CORONARY THROMBOLYSIS has recently received great attention for its potential reduction of the1 extent of necrosis after myocardial ischemia. Thrombolysis can be accomplished by infusion of streptoki-

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“…Despite this brilliant clinical result, the hypothesis of the open artery in the AMI had often been questioned. Initial studies on early coronary patency revealed that t-PA (tissue plasminogen activator) was more efficient than streptokinase 138,139 . However, there was no difference in the mortality indices between these two thrombolytic agents in large-scale randomized studies, such as GISSI II 140 and ISIS III 141 .…”

Section: Thrombolysismentioning

confidence: 99%

Acute ischemic syndromes

Fd¹

1999

Arq. Bras. Cardiol.

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Randomised Trial of Intravenous Recombinant Tissue-Type Plasminogen Activator Versus Intravenous Streptokinase in Acute Myocardial Infarction

Cited by 721 publications

References 23 publications

Design of Potent Bivalent Thrombin Inhibitors Based on Hirudin Sequence: Incorporation of Nonsubstrate-Type Active Site Inhibitors

Design of Potent Bivalent Thrombin Inhibitors Based on Hirudin Sequence: Incorporation of Nonsubstrate-Type Active Site Inhibitors

Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis.

Acute ischemic syndromes

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