Ultraslow thrombolytic therapy: A novel strategy in the management of PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE: The Ultra-slow PROMETEE trial

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Abstract

Low-dose (25mg), slow infusion (6hours) of tissue-type plasminogen activator (t-PA) with repetition as needed has been shown to provide effective and safer thrombolysis in patients with prosthetic valve thrombosis (PVT). Further prolonging the infusion time may be rational with regard to reducing complication rates without reducing success rates. We aimed to investigate the efficacy and safety of ultraslow (25hours) infusion of low-dose (25mg) alteplase (t-PA) for PVT.

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A comparison of reteplase with alteplase for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators.

P. Probst, H Emanuelsson, D. Ardissino … (1997)

Reteplase (recombinant plasminogen activator), a mutant of alteplase tissue plasminogen activator, has a longer half-life than its parent molecule and produced superior angiographic results in pilot studies of acute myocardial infarction. In this large clinical trial, we compared the efficacy and safety of these two thrombolytic agents. A total of 15,059 patients from 807 hospitals in 20 countries who presented within 6 hours after the onset of symptoms with ST-segment elevation or bundle-branch block were randomly assigned in a 2:1 ratio to receive reteplase, in two bolus doses or 10 MU each given 30 minutes apart, or an accelerated infusion of alteplase, up to 100 mg infused over a period of 90 minutes. The primary hypothesis was that mortality at 30 days would be significantly lower with reteplase. The mortality rate at 30 days was 7.47 percent for reteplase and 7.24 percent for alteplase (adjusted P=0.54; odds ratio, 1.03; 95 percent confidence interval, 0.91 to 1.18). The 95 percent confidence interval for the absolute difference in mortality rates was -1.1 to 0.66 percent. Stroke occurred in 1.64 percent of patients treated with reteplase and in 1.79 percent of those treated with alteplase (P= 0.50). The respective rates of the combined end point of death or nonfatal, disabling stroke were 7.89 percent and 7.91 percent (P=0.97; odds ratio, 1.0; 95 percent confidence interval, 0.88 to 1.13). As compared with an accelerated infusion of alteplase, reteplase, although easier to administer, did not provide any additional survival benefit in the treatment of acute myocardial infarction. Other results, particularly for the combined end point of death or nonfatal, disabling stroke, were remarkably similar for the two plasminogen activators.

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Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial

Frans Van de Werf (1999)

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Treatment of obstructive thrombosed prosthetic heart valve.

Grace Huang, Hartzell V Schaff, Thoralf M. Sundt … (2013)

Obstructive thrombosed prosthetic heart valve (OTPHV) is a serious complication of heart valve replacement. There are no generally accepted criteria for management of these patients. Therefore, in September 2012, a literature survey of studies published after 1995 was performed to analyze the data regarding clinical outcomes of patients with OTPHV treated with thrombolytic agents and with surgery since 1996. The search yielded appropriate and relevant studies, which included 17 studies comprising 756 patients who had received thrombolytic therapy and 13 studies comprising 662 patients who had received surgery. The data on these 2 groups was analyzed in detail relating to frequency of use of the diagnostic studies, baseline patient data, and on the rate of complete success, outcomes, and complications of the therapy they had received, and the limitations of the studies. We have then developed a strategy for therapy of OTPHV.