Jürgen Windeler

Randomized, Double-Blind Study Comparing Saruplase With Streptokinase Therapy in Acute Myocardial Infarction: The COMPASS Equivalence Trial

Abstract Objectives. This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. Background. The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. Methods. Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for Results. Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p Conclusions. Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

Comparison of Saruplase and Alteplase in Acute Myocardial Infarction

Four hundred seventy-three patients with acute myocardial infarction (AMI) were treated with either saruplase (80 mg/hour, n = 236) or alteplase (100 mg every 3 hours, n = 237). Comedication included heparin and acetylsalicylic acid. Angiography was performed at 45 and 60 minutes after the start of thrombolytic therapy. When flow was insufficient, angiography was repeated at 90 minutes. Coronary angioplasty was then performed if Thrombolysis In Myocardial Infarction (TIMI) trial 0 to 1 flow was seen. Control angiography was at 24 to 40 hours. Baseline characteristics were similar. Angiography showed comparable and remarkably high early patency rates (TIMI 2 or 3 flow) in both treatment groups: at 45 minutes, 74.6% versus 68.9% (p = 0.22); and at 60 minutes 79.9% versus 75.3% (p = 0.26). Patency rates at 90 minutes before additional interventions were also comparable (79.9% and 81.4%). Angiographic reocclusion rates were not significantly different: 1.2% versus 2.4% (p = 0.68). After rescue angioplasty, angiographic reocclusion rates of 22.0% and 15.0% were observed. Safety data were similar for both groups. Thus, (1) early patency rates were high for saruplase and alteplase treatment, (2) reocclusion rates for both drugs were remarkably low, and (3) complication rates were similar. Thus, saruplase seems to be as safe and effective as alteplase.

Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (saruplase) in acute myocardial infarction : influence of heparin on early patency rate (LIMITS study)

OBJECTIVES The Liquemin in Myocardial Infarction During Thrombolysis With Saruplase (LIMITS) study was instituted to evaluate and characterize the effect of a prethrombolytic heparin bolus (5,000 IU) on the efficacy and safety of saruplase in patients with acute myocardial infarction. BACKGROUND Heparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct-related artery. METHODS The study was designed as a randomized, parallel-group, double-blind, multicenter trial. Patients were treated within 6 h of onset of symptoms with either a bolus of 5,000 IU of heparin (Liquemin) (n = 56, HSH group) or placebo (n = 62, PSH group) before thrombolytic treatment with saruplase given as a 20-mg bolus followed by an infusion of 60 mg over 60 min. Thirty minutes after completion of thrombolysis, an intravenous heparin infusion was administered for 5 days. Before coronary angiography was performed at 6 to 12 h after start of lysis, an additional bolus of 5,000 IU heparin was given to all patients. End points studied were patency of the infarct-related artery, changes in the hemostatic system and bleeding complications. RESULTS In the HSH group (heparin-saruplase-heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 or 3) compared with 56.5% in the PSH group (placebo-saruplase-heparin) (intention-to-treat analysis, p = 0.01). No significant difference was observed between the two groups with regard to changes in fibrinogen and fibrin/fibrinogen degradation products. A total of eight bleeding complications (14.3%) were observed in the HSH group and five (8.1%) in the PSH group; no cerebrovascular event occurred, and no allergic reaction was reported. A total of 12 patients died during the hospital stay, 3 in the HSH group (5.4%) and 9 in the PSH group (14.5%). CONCLUSIONS In acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.

A double-blind multicenter comparison of the efficacy and safety ofsaruplase andurokinase in thetreatment ofacutemyocardialinfarction: Report of the SUTAMI study group

Background: Urokinase or two-chain urokinasetype plasminogen activator has been shown to be effective in the treatment of acute myocardial infarction. Its parent molecule, single-chain urokinase-type plasminogen activator (scu-PA), unlike urokinase, can selectively activate fibrinbound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to urokinase and by further plasmin generation. The aim of our study was to compare the efficacy and safety of recombinant unglycosylated scu-PA, or saruplase, and urokinase at doses considered optimal in patients with acute myocardial infarction within 6 hours of onset of pain. Methods and results: In a double-blind trial 543 patients were randomized to saruplase (20 mg bolus + 60 mg/hr) or urokinase (1.5 million unit bolus + 1.5 million units/hr). Primary endpoint: The patency rates at 24–72 hours were 75.4% (95% CI 70.3–80.5%) for saruplase and 74.2% (95% CI 69.0–79.4%;P=0.77) for urokinase. Secondary endpoint: The incidence of bleeding events in both groups was 10.7%. There were three hemorrhagic strokes in the saruplase group (ns). Other efficacy and safety evaluations: Apart from the generation of more fibrinogen degradation products under saruplase, the changes in hemostatic parameters did not differ. Hospital mortality was 4.4% for saruplase and 8.1% for urokinase. This nonsignificant difference was maintained for 1 year. Conclusion: The efficacy and safety of saruplase and urokinase in the regimens used are very similar.

Thrombolysis with saruplase versus streptokinase in acute myocardial infarction: Five-year results of the PRIMI Trial ☆ ☆☆ ★ ★★

BACKGROUND Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. METHODS AND RESULTS Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. CONCLUSIONS Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period.

Anwendung diagnostischer Tests

Wie an vielen Stellen dieses Buches ausgefuhrt. setzt sich die quantitativ verwertbare diagnostische Information (pradiktiver Wert) aus einem uber und Spezifitat) und der Ausgangswahrscheinlichkeit (A-priori-Wahrscheinlichkeit, Pravalenz) zusammen, Jede diagnostische Masnahme wird also erst sinnvoll in der Zusammensetzung dieser beiden Informationen.

Entstehung von Hypothesen für diagnostische Tests

Vor einer Prufung diagnostischer Tests, mit deren Methodologie und Durchfuhrung sich dieses Buch befast, sollte die Formulierung der zu prufenden Hypothese stehen. Das folgende Kapitel zeigt Mechanismen auf, die zur Entstehung von Hypothesen beitragen konnen.

Die kontrollierte diagnostische Studie (Phase 3)

Studien zur Phase 3 der Evaluierung diagnostischer Verfahren bauen auf den Ergebnissen der Phasen 1 und 2 auf. Nachdem in der Phase 2 die grundsatzliche Eignung eines Laborparameters, eines neuen apparativen Verfahrens oder einer speziellen klinischen Beobachtung als diagnostische Masnahme untersucht wurde, findet in der Phase 3 die eigentliche Evaluierung einer solchen Methode statt.

Kritische Beurteilung publizierter diagnostischer Tests

In medizinisch-klinischen Zeitschriften nehmen Publikationen uber Prufungen von diagnostischen Masnahmen einen breiten Raum ein. Methodische Unzulanglichkeiten sind dabei oft nicht auf den ersten Blick erkennbar. Das methodische Mangel sehr verbreitet sind, konnte kurzlich anhand einer Uberprufung zweier Jahrgange von 4 fuhrenden deutschsprachigen medizinischen Zeitschriften belegt werden [68]. Zur Beurteilung der Validitat der Aussage diagnostischer Studien ist es meist unerlaslich, sich ein genaues Bild uber die angewandte Methodik und die Durchfuhrung der Studie zu machen. Im folgenden soll zusammengestellt werden, welche Einzelfragen hierbei kritisch zu betrachten sind. Diese sind in den verschiedenen Phasen der Evaluierung sehr unterschiedlich. Darum ist es besonders wichtig, sich Klarheit daruber zu verschaffen, auf welcher Stufe der Evaluierung im Sinne der oben dargestellten Phasen 1 – 4 die Studie einzuordnen ist.

Grundlagen der Wahrscheinlichkeitstheorie

In diesem Abschnitt wird die wichtigste Grundlage fur die klinische Entscheidungsfindung diskutiert: die Wahrscheinlichkeit.