More Rapid, Complete, and Stable Coronary Thrombolysis With Bolus Administration of Reteplase Compared With Alteplase Infusion in Acute Myocardial Infarction

Smalling, Richard W.; Bode, Christoph; Kalbfleisch, John M.; Sen, Semi; Limbourg, P; Forycki, Florian; Habib, Gabriel B.; Feldman, Robert L.; Hohnloser, Stefan H.; Seals, A. Allen

doi:10.1161/01.cir.91.11.2725

Cited by 256 publications

(98 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30,31 The Recombinant Plasminogen Activator Angiographic Phase II International Dos Finding Study (RAPID) I trial showed that r-PA, when given as a double bolus of 10ϩ10ϫ10 6 U 30 minutes apart, achieves more rapid, complete, and sustained thrombolysis than standard-dose alteplase (100 mg over 3 hours). 32 In the RAPID II trial, the same r-PA dose regimen yielded 90-minute reperfusion rates that were higher than those of front-loaded rt-PA (59.9% versus 45.2%, Pϭ0.01). 33 These promising angiographic findings notwithstanding, r-PA did not achieve superior mortality or clinical outcomes compared with SK (1.5ϫ10 6 U over 60 minutes) in the International Joint Efficacy Comparison of Thrombolytics (INJECT) study.…”

Section: Mutants and Variants Of Rt-pamentioning

confidence: 99%

Fibrinolysis for Acute Myocardial Infarction

Armstrong

Collen

2001

Circulation

View full text Add to dashboard Cite

Section: Mutants and Variants Of Rt-pamentioning

confidence: 99%

Fibrinolysis for Acute Myocardial Infarction

Armstrong

Collen

2001

Circulation

View full text Add to dashboard Cite

“…4,5 Early treatment and complete TIMI grade 3 flow have been facilitated by faster delivery regimens for accelerated alteplase 3 and double-bolus reteplase. [6][7][8] Simpler effective regimens, such as a single-bolus injection, may offer additional benefits through earlier achievement of reperfusion and by reduction in the risk of dosing errors. Efforts to improve thrombolytic efficacy are tempered by the risk of serious bleeding, particularly hemorrhagic stroke.…”

mentioning

confidence: 99%

Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction

et al. 1998

Self Cite

View full text Add to dashboard Cite

Background —Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results —InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P <0.001). Similar results were observed at 90 minutes (26.1% to 57.1%, P <0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. Conclusions —Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

show abstract

“…A double bolus regimen (10 C 10 mega units after 30 min) of r-PA administered to patients with AMI helped in complete, speedy, and sustained thrombolysis in comparison with the standard dose of t-PA (front-loaded accelerated infusion or standard infusion). 85,86 This strategy helped to overcome the necessity of a continuous intravenous infusion. The double bolus regimen of r-PA was found to be as effective as the standard dosage of streptokinase (1.5 million units given intravenously over 60 min) for the treatment of AMI (The INJECT Trial, 1995).…”

Section: Third Generation Plasminogen Activatorsmentioning

confidence: 99%

The evolution of recombinant thrombolytics: Current status and future directions

Adivitiya

Khasa

2016

Bioengineered

View full text Add to dashboard Cite

Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

show abstract

More Rapid, Complete, and Stable Coronary Thrombolysis With Bolus Administration of Reteplase Compared With Alteplase Infusion in Acute Myocardial Infarction

Cited by 256 publications

References 27 publications

Fibrinolysis for Acute Myocardial Infarction

Fibrinolysis for Acute Myocardial Infarction

Evaluation of a Weight-Adjusted Single-Bolus Plasminogen Activator in Patients With Myocardial Infarction

The evolution of recombinant thrombolytics: Current status and future directions

Contact Info

Product

Resources

About