A comparison of recombinant Hirudin with Heparin for the treatment of acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators

BACKGROUND: Thrombin has a pivotal role in the pathogenesis of acute coronary thrombosis. We compared the clinical efficacy of a potent, direct thrombin inhibitor, recombinant hirudin, with that of heparin (an indirect antithrombin agent) in patients with unstable angina or acute myocardial infarction. METHODS: At 373 hospitals in 13 countries, 12,142 patients with acute coronary syndromes were randomly assigned to 72 ho

Genezen is beter dan voorkomen

In de tweede helft van de vorige eeuw waren hart en vaatziekten de belangrijkste doodsoorzaak in Nederland. Dit is lang zo gebleven, maar na een piek rond 1970 is de sterfte aan hart en vaatziekten, gecorrigeerd voor de leeftijd, gedaald en sinds enkele jaren staan hart en vaatziekten op de tweede plaats wat betreft de sterfte percentages. (figuur 1) Dit is een verdienste van de cardiologie en de vasculaire geneeskunde. De levensverwachting in Nederland en in andere westerse landen is in die jaren belangrijk toegenomen. Dat komt vooral door enorme verbeteringen in de preventie en behandeling van hart en vaatziekten in 40 jaar. De helft van deze winst komt door betere preventie en de helft door betere behandeling van de ziekte. Afscheidsrede Prof. dr. Maarten L. Simoons hoogleraar Cardiologie Erasmus Universiteit Rotterdam, uitgesproken 17 december 201

A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction

BACKGROUND: Among physicians who treat patients with acute myocardial infarction, there is controversy about the magnitude of the clinical benefit of primary (i.e., immediate) coronary angioplasty as compared with thrombolytic therapy. METHODS: As part of the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) trial, we randomly assigned, 1138 patients from 57 hospitals who presented within 12 hours of acute myocardial infarction (with ST-segment elevation on the electrocardiogram) to primary angioplasty or accelerated thrombolytic therapy with recombinant tissue plasminogen activator (t-PA). We also randomly assigned 1012 patients to heparin or hirudin treatment in a factorial design. The primary study end point was a composite outcome of death, nonfatal reinfarction, and nonfatal disabling stroke at 30 days. RESULTS: The incidence of the primary end point in the angioplasty and t-PA groups was 9.6 percent and 13.7 percent, respectively (odds ratio, 0.67; 95 percent confidence interval, 0.47 to 0.97; P = 0.033). Death occurred in 5.7 percent of the patients assigned to angioplasty and 7.0 percent of those assigned to t-PA (P=0.37), reinfarction in 4.5 percent and 6.5 percent (P=0.13), and disabling stroke in 0.2 percent and 0.9 percent (P=0.11). At six months, there was no significant difference in the incidence of the composite outcome (13.3 percent vs. 15.7 percent, P not significant) [corrected]. The primary end point was observed in 10.6 percent of the patients in the angioplasty group assigned to heparin and 8.2 percent of those assigned to hirudin (P=0.37). CONCLUSIONS: This trial suggests that angioplasty provides a small-to-moderate, short-term clinical advantage over thrombolytic therapy with t-PA. Primary angioplasty, when it can be accomplished promptly at experienced centers, should be considered an excellent alternative method for myocardial reperfusion

Should all patients with an acute myocardial infarction be referred for direct PTCA?

All randomised comparisons have shown that direct PTCA is superior to thrombolysis in patients with AMI. Yet the choice of treatment strategy should depend on the careful evaluation of the risk/benefit of treatment. Issues unrelated to this assessment will most likely influence the selection of treatment in daily practice. Two algorithms have been proposed which differ in the primary selection or triage criterion (area at risk versus time interval). Based upon local and regional factors, one or the other may be chosen. The role of rescue and systematic PTCA after thrombolysis needs further elucidation. At present, it cannot be proposed as a standard treatment

Benefits and risks of thrombolysis for acute myocardial infarction

Thrombolytic therapy is a major step forward in the treatment of acute myocardial infarction and may result in up to 50% mortality reduction, provided that it is administered early (chapter 1). In 80 to 85% of patients with suspected acute myocardial infarction, a coronary artery is blocked by a clot. With thrombolytic therapy the closed coronary artery is desobstructed in may cases, is infarct size limited and left ventricular function preserved. Several thrombolytic agents are available for clinical use: streptokinase, APSAC, urokinase and more recently recombinant tissue-type plasminogen activator (rt-PA or alteplase). The latter is the genetically engineered natural occurring plasminogen activator. Which agent is superior is still a matter of debate. Unlike streptokinase, APSAC and urokinase, rt-PA dissolves blood clots without degradation of circulating fibrinogen during in vitro and in animal experiments, provided that the dose does not exceed a certain threshold. This property of rt-PA is called fibrin

The Need for Resources for Clinical Research

The medical profession, in particular cardiologists, acknowledge the fact that during the last 30 years, much of the progress made in the field of medicine has resulted from fruitful and close collaboration between academia and the pharmaceutical industry. However, during the last decade, this relationship has changed considerably. The industry increasingly carries out its own research, development of drugs and trials, according to its own agenda. As a result, academia has lost its influence. This has led to a dramatic increase in the cost of clinical randomised trials. In the meantime, academic careers and research have become less attractive to physicians. Funding for research is increasingly devoted to basic science, in particular genomics, and little is left for clinical research. As a result, many important clinical trials in various areas of medicine, including cardiology, remain unfunde