RESUMO
Background: The current prevalence, timing, and route of heparin use after thrombolytic therapy for acute myocardial infarction both within and outside the United States (U.S.) have not been extensively studied. Method: An 18-item questionnaire was mailed to cardiologists and emergency medicine practitioners in the U.S. and to physicians in 5 countries considering participation in an international trial of thrombolytic therapy. Results: Almost all used some form of heparin after recombinant tissue-plasminogen activator; 8% withheld heparin after streptokinase. Non-U.S. physicians used subcutaneous heparin more frequently than did U.S. physicians (26% vs. 4%). Time to heparin initiation varied greatly. Most physicians used the activated partial thromboplastin time to monitor anticoagulation, although there was little consensus about the appropriate way to determine the efficacy of heparin therapy. Conclusions: This survey shows considerable disagreement about the preferred administration of heparin among physicians treating patients with myocardial infarction. This lack of agreement reflects uncertainty about how heparin therapy should be used. When the results of well-designed clinical trials examining the optimal dosing, timing, and monitoring of heparin therapy have been published, perhaps the clinical community can reach a consensus.
RESUMO
Variations in the management of patients with chest pain and acute myocardial infarction (MI) can significantly affect hospital length of stay and cost. Risk stratification of such patients, combined with data about effective therapies, provides the basis for developing rational guidelines for patient care that can improve efficiency while maintaining quality of care. Such standardized management approaches are often referred to as pathways or CareMaps. To be most effective in guiding hospital course and early discharge planning, risk stratification strategies must be applied early in a patient's course with continuous updating. The process of identifying risk in a patient with acute chest pain occurs in two segments: assessing the risk of acute MI at presentation, and subsequently assessing the morbidity and mortality risk of patients diagnosed with acute MI. Identification of patient risk at presentation has been the object of intense investigation. The history, physical exam, initial electrocardiogram, and cardiac enzymes are the mainstays of the process, but because of inherent weaknesses in this approach (>25% of acute MIs missed initial screening), several risk stratification models have been developed. To date these models have not been widely employed, however. Very sensitive early cardiac markers, such as troponin T, and the use of diagnostic echocardiography or cardiolite perfusion imaging during pain are also being investigated. Chest pain observation units are an alternate strategy and have obviated the need to admit many low- to moderate-risk chest pain patients. In these protocol-driven units, continuous physiologic monitoring and serial cardiac enzymes and electrocardiography over a 9-12 hour period refine the risk assessment. For the majority who "rule out," the risk of subsequent MI or death is very low. Cost savings due to reduced length of stay and more efficient resource utilization are 63-76% compared with conventional word or cardiac care unit management. For patients with acute MI, baseline characteristics, complications, and laboratory and diagnostic testing help define the risk of morbidity and mortality and guide management through the immediate post-MI phase and long term. Many models incorporating these features have been proposed for risk stratification after acute MI, and they have implications for both timing of discharge and necessary diagnostic testing. Savings by employing risk stratification to guide hospital course and discharge planning could be 30-44% in some patient groups. In conclusion, risk stratification models can facilitate early discharge planning, potentially reducing hospital stay, improving resource utilization, and reducing costs.
RESUMO
The benefits of thrombolytic therapy in the treatment of acute myocardial infarction are incontrovertible. Large-scale studies combining angiographic and clinical end-points have demonstrated a perfusion-mortality relationship, with the highest survival rate among patients with early restoration of TIMI grade 3 coronary arterial flow. Despite advances in thrombolytic strategies, a substantial number of patients fail to rapidly achieve and maintain adequate coronary perfusion with thrombolysis. Conjunctive therapy with aspirin has proven useful in thrombolytic regimens, likely countering the heightened platelet activity central to acute coronary syndromes. The antiplatelet effect of aspirin is relatively weak compared with that of glycoprotein IIb/IIIa platelet receptor antagonists, which block the final common pathway of platelet aggregation. Lamifiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist. In early experimental studies, Lamifiban in combination with thrombolytic therapy has been shown to effectively restore coronary arterial patency, and phase I and phase II data have shown its use to be safe. To determine the optimal dose with regard to safety and efficacy of Lamifiban to be used with thrombolytic therapy in a large-scale trial, a phase II study is underway. The Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study is a randomized, placebo-controlled study of Lamifiban in 400 patients receiving thrombolysis as treatment for acute myocardial infarction. By studying 90-minute angiography, platelet aggregation, continuous electrocardiography, and clinical outcome in PARADIGM, important insights will be obtained to determine the optimal dose of Lamifiban for phase III study. We provide the background and rationale for the study of Lamifiban in PARADIGM and other ongoing studies in acute coronary syndromes.