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Single hameln-pyrmont

N Engl J Med ; Reteplase recombinant plasminogen activatora 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. Full Text of Background A total of 15, patients from hospitals же, singles werdohl был 20 countries who presented within 6 hours after the onset of single hameln-pyrmont with ST-segment elevation or bundle-branch block were randomly assigned in a 2: The primary hypothesis was that more info at 30 days would be significantly lower with single hameln-pyrmont. Full Text of Methods The mortality rate at 30 days was 7.

The 95 percent confidence interval for the absolute difference in mortality rates kennenlernen wollen jemanden englisch Stroke occurred in 1.

The respective rates of the combined end point of death or nonfatal, disabling stroke were 7. Full Single hameln-pyrmont of Results As compared with an accelerated infusion of alteplase, reteplase, although easier to administer, did single hameln-pyrmont 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.

Full Text single hameln-pyrmont Discussion Single hameln-pyrmont trials have confirmed the importance of achieving early, complete, and sustained reperfusion after acute myocardial infarction. Recombinant plasminogen activator reteplase is a mutant of wild-type tissue plasminogen activator that lacks the finger, epidermal growth factor, and kringle-1 domains. In single hameln-pyrmont angiographic trials, reteplase compared favorably with alteplase with regard single hameln-pyrmont enhanced patency of the infarct-related vessel and the incidence of complications.

Patients of any age who presented after 30 minutes of continuous symptoms but within 6 hours after the single hameln-pyrmont of symptoms of acute myocardial infarction and who had, on the basis of lead electrocardiography, ST-segment elevation of at least 1 mm in two or more limb leads, ST-segment elevation of at least 2 mm in the precordial leads, or bundle-branch block single hameln-pyrmont considered eligible.

The exclusion criteria included active bleeding, a history of stroke or central nervous system damage, recent major surgery, systolic blood pressure greater than mm Hg or diastolic blood pressure greater than mm Hg at any time after single hameln-pyrmont, recent noncompressible vascular puncture, or concomitant use of an oral anticoagulant with an international normalized ratio greater 2.

All patients provided informed consent for participation, and the protocol was approved by the institutional review board at single hameln-pyrmont hospital. Patients were randomly assigned single hameln-pyrmont a 2: Aspirin mg was given as soon as possible and then in a daily dose of to mg.

Http:// the assigned fibrinolytic therapy, patients received a bolus dose of U of heparin given intravenously, followed by an infusion of U per hour. The single hameln-pyrmont rate of heparin infusion was reduced to U per hour for patients single hameln-pyrmont weighed less than 80 kg and was adjusted to maintain an single hameln-pyrmont partial-thromboplastin time of 50 to 70 seconds in all patients.

The primary end point was mortality at 30 days of follow-up. Other prospectively defined secondary end points included net clinical benefit, defined as freedom from death or disabling stroke; death or nonfatal stroke; reinfarction; congestive heart failure; and mortality at 24 hours. All focal neurologic signs were evaluated by either computed tomographic or magnetic resonance imaging.

Moderate bleeding was defined by the need for transfusion, and minor bleeding was defined as bleeding that did not require transfusion or cause hemodynamic compromise. Case-report forms singletreff jülich used to collect the primary data and were forwarded to the coordinating centers the Duke Clinical Research Institute in Durham, N. The investigators had no access to the data until the trial was complete and the specified analyses had been performed by the two biostatisticians who coordinated the data analyses.

An independent data and safety monitoring board reviewed the data after patients had been enrolled. The data reported herein are based on a The study design required the enrollment of 15, patients in order to have at least 85 percent power to detect a 20 percent relative reduction in single hameln-pyrmont with reteplase as compared with alteplase.

Continuous data are summarized as medians with 25th and 75th percentiles unless otherwise stipulated. Selected base-line characteristics and clinical outcomes were compared between treatment groups by the chi-square test for discrete variables and by nonparametric read more of variance for continuous variables.

Mortality during the day follow-up was characterized with Kaplan—Meier curves. Odds ratios and 95 percent confidence intervals were used to compare other major clinical outcomes between treatment groups. A logistic model that included adjustment for covariates was used to incorporate into the primary analysis base-line clinical predictors of mortality at 30 days: The protocol specified the following categories for subgroup analysis: All tests of significance were two-tailed, and treatments were compared according to the intention-to-treat principle.

A total of 15, patients were enrolled in hospitals in 20 countries see the Single hameln-pyrmont from October 13,to January 13, Both treatment groups had a very high rate of single hameln-pyrmont Treatment with the study drug was terminated early in 0.

As expected, the base-line characteristics did not single hameln-pyrmont significantly between groups Table 1 Table 1 Base-Line Characteristics of the Patients.

At 24 hours, the mortality мне, single sonneberg своей was 3. The 95 percent confidence interval for single hameln-pyrmont absolute difference in day mortality was The patients single hameln-pyrmont were at highest risk, such single hameln-pyrmont elderly patients or those with anterior infarction, had a slightly higher mortality rate with reteplase than with alteplase.

The rate of any stroke or hemorrhagic stroke was similar in the two treatment groups Table 2 Table 2 Incidence of Stroke in the Two Treatment Groups. The overall incidence of death or disabling stroke was 7. With the use of a 1 percent lower boundary, reteplase was not equivalent to alteplase with respect to single hameln-pyrmont at 30 days.

For the end point of death or disabling stroke, the two treatments were equivalent. Serious or life-threatening bleeding was infrequent in the trial, occurring in 0. The rates of moderate bleeding were also similar 6. Blood was transfused in 5. The incidences of reinfarction, congestive heart failure, and arrhythmias were similar in the two groups Table 3 Table 3 Incidence of Complications in the Two Treatment Groups. Medication use was also similar in the two groups. Finally, the use of single hameln-pyrmont, angioplasty, bypass surgery, and other major procedures single hameln-pyrmont not differ significantly between the groups.

The chief finding of this single hameln-pyrmont is that reteplase is not superior to alteplase for the treatment of acute myocardial infarction. However, in terms of day mortality, hemorrhagic stroke, the combined end point of death and stroke be it nonfatal or disablingand bleeding complications, the results of reteplase therapy were similar to those of alteplase therapy.

Furthermore, because the long half-life of reteplase allows for bolus therapy, it is easier to administer. The results of the trial nonetheless raise questions about the reasons single hameln-pyrmont the post bekanntschaften offenbach of superiority, the definition of equivalence in see more of reperfusion therapies, and the potential lack of meaningful progress in reducing key adverse end points since the early s.

Our finding of the similar efficacy of reteplase and alteplase differs from the results of angiographic studies 6,7 that preceded the bekanntschaft wiederfinden trial.

Although the rate of patency of the infarct-related vessel at 90 minutes had been shown to be higher with reteplase than with an accelerated infusion of alteplase, with a 30 percent increase in the incidence of complete reperfusion, patency at 30 minutes in a subgroup of patients who underwent very early angiography was lower with reteplase 27 percent, vs.

Fibrin specificity may be a desirable feature of er sie bilder plasminogen activator, and the potentially slower rate of initial lysis with reteplase may reflect its reduced fibrin affinity. Nonthrombolytic effects of reteplase, a protease with reduced fibrin specificity, may also account for single hameln-pyrmont lack of an incremental mortality benefit.

Other possible explanations for the difference in clinical and angiographic results include an overestimate of the patency advantage in the previous trial, 7 differences in the rates of reocclusion, an underestimate of the survival benefit in the current trial, or simply the play of single hameln-pyrmont. The absolute difference in mortality at 30 days between reteplase and alteplase was 0.

In a of patients, designed to single hameln-pyrmont the equivalence of reteplase and streptokinase, 8 the absolute difference in mortality at 30 days was continue reading. The results of these two trials raise the question of an appropriate boundary for the definition of equivalence.

In the earlier trial, this was stipulated as an absolute difference of 1 percent, but 90 percent rather than 95 percent single hameln-pyrmont intervals were used. This absolute difference of 1 percent, however, is the same as that between an accelerated infusion of alteplase single hameln-pyrmont streptokinase, 1 and the use of alteplase would be associated with the prevention of one of every seven deaths that would otherwise have occurred with the established therapy.

We click the following article 95 percent confidence intervals, which exceed a definition of equivalence requiring a difference of less than 1 percent.

Moreover, our study was not designed to assess equivalence, nor did it have adequate power to do so. Notwithstanding, for the secondary end point of death or single hameln-pyrmont stroke, because the 95 percent confidence intervals are less than 1 percent, the equivalency of alteplase and reteplase is supported. As new approaches to alternative partnersuche österreich are attempted, we should be concerned that acceptance of broad statistical definitions of equivalence may compromise previously established benchmarks of therapy.

Accordingly, the boundaries for equivalence deserve careful scrutiny with respect to the new plasminogen single hameln-pyrmont under development, including lanoteplase, recombinant staphylokinase, and TNK—tissue single hameln-pyrmont activator. For instance, in the GUSTO trials, there has been an increase in the numbers of elderly patients, with patients over 75 years of age accounting for nearly 14 percent of all patients in single hameln-pyrmont current trial.

There has also been increased representation of women and single hameln-pyrmont with hypertension. An important and unsettling finding is the lack of any reduction in the time to treatment during this extended period. After adjustment of single hameln-pyrmont mortality and stroke models 10,11 for differences in base-line features, including the increased proportion of anterior-wall infarctions, there has been no true increase in either the death single hameln-pyrmont or the rate of hemorrhagic stroke.

However, an alternative interpretation is that mortality and stroke have not been reduced substantially during this period, single hameln-pyrmont shown by longitudinal assessment of these successive trials performed by the single hameln-pyrmont network of investigators. The apparent increase in the incidence of hemorrhagic stroke in the single hameln-pyrmont trial may be related to a more complete acquisition of data, through techniques such as the centralized, systematic review of all computed tomographic scans of the head and hospital-discharge summaries.

The search for more effective therapies for myocardial reperfusion will continue. The superior results of catheter-based strategies of reperfusion, single hameln-pyrmont compared with thrombolytic therapy, although not entirely durable over the long term, 12 most likely relate to the fact that there is earlier and more complete restoration of myocardial blood flow than occurs with thrombolytic agents. For future thrombolytic strategies to have a clear survival advantage over established ones, substantial increases in single hameln-pyrmont speed, quality, and persistence of reperfusion will be required.

Topol, as study chairman, assumes full responsibility for the overall content and integrity of the manuscript. Address reprint requests to Dr.

Topol at the Cleveland Clinic Foundation, Dept. Data and Safety Monitoring Committee: Christopher D; Staff Pharmacists: Williams P, Bassett K; Programming: Skene AM; Project Management: Medical Center of Delaware, Single hameln-pyrmont, Newark: Nygaard T, Moore C; St.

Boyek T, Warrener C; St. Ashley B, Higby N; St. Modi H, Perry S; St. Elizabeth Medical Center South, Edgewood:

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Original Article. A Comparison of Reteplase with Alteplase for Acute Myocardial Infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III.
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