Pharmacy & Therapeutics - September 2008 - (Page CB4)

CLINICAL QUESTION & ANSWER FEATURED EXPERT Charles V. Pollack, Jr., MD Professor of Emergency Medicine University of Pennsylvania School of Medicine Charles V. Pollack, MD, is Professor of Emergency Medicine at the University of Pennsylvania and Chairman, Department of Emergency Medicine, at Pennsylvania Hospital in Philadelphia. Dr Pollack received his undergraduate degree in Chemistry and History from Emory University, Atlanta, where he also earned a Master’s degree in History. He completed his medical training at Tulane University School of Medicine, New Orleans, Louisiana, and his emergency medicine residency at the University of Mississippi in Jackson. What is STEMI and what does it mean for patients in terms of prognosis and risk for recurrent MI? ST-segment elevation MI--the classic “heart attack”--reﬂects transmural injury and does not always present with typical symptoms. The symptoms usually include chest pain, but occasionally patients may have jaw or arm pain, shortness of breath, or nausea without chest pain. By deﬁnition, all STEMI patients have abnormal electrocardiograms (ECG), showing either ST-segment elevation in contiguous leads, or a new (or presumed new) left bundle branch block on the ECG, which indicates that the patient is at signiﬁcant risk of short-term mortality. There also is the likelihood of recurrence due to the atherosclerotic burden that caused the primary event. About half a million cases of STEMI per year are recorded.1 The prognosis for STEMI depends on a number of factors including patient age and the location of the infarct. Generally, patients suffering from anterior wall infarcts have a poorer prognosis. What are the options, both pharmacological and mechanical, for reperfusion therapy in STEMI patients? Reperfusion can be achieved in 2 basic ways: pharmacologic, with a ﬁbrinolytic agent that is given intravenously (IV) to dissolve the clot in the coronary artery, or mechanical, by “direct” or “primary” percutaneous coronary intervention (PCI), performed in the cardiac catheterization lab. Fibrinolytic therapy is the more common type of STEMI reperfusion therapy in the US and worldwide, and, in the absence of the availability of rapid and expert primary PCI, is the standard-ofcare management for patients with STEMI. Contraindications to ﬁbrinolytic therapy are based on bleeding risk and hemodynamic stability. All ﬁbrinolytic agents work by breaking down the thrombin and ﬁbrin inside the platelet aggregates at the site of obstruction. Fibrin-speciﬁc lytic agents (reteplase, alteplase, and tenecteplase) are preferred in the US, while streptokinase is used less often, although its use worldwide remains relatively common. An anticoagulant is necessary to prevent ongoing coagulation in the affected area. Additionally, for a period of time after clot dissolution, patients remain in a hypercoagulable state because of the physiologic condition that caused the STEMI and because thrombogenic factors are released when ﬁbrin and thrombin are dissolved. It is common to use anticoagulation with ﬁbrin-speciﬁc ﬁbrinolytics, but in the past, not with streptokinase. In choosing between ﬁbrinolytic therapy and PCI, there is an easy bottom line: if PCI is readily available, it is the reperfusion therapy of choice. However, there are many cases in which PCI is not readily available and ﬁbrinolytic therapy is a safe and effective alternative. In fact, the earlier patients can receive ﬁbrinolytic therapy, the more likely they are to beneﬁt from it. Guidelines from the ACC/AHA state that the standard target for “door-to-balloon” time (arrival at ED to catheterization lab with access established) for direct PCI should be no longer than 90 minutes. For ﬁbrinolytic therapy, the lytic agent should be ready to inject (“door-to-needle” time) within 30 minutes of arriving at the ED.1 What was the objective of this study? In the “lytic era,” the anticoagulant most commonly used with ﬁbrinolysis has been UFH. The objective of the ExTRACT study2 was to determine whether Lovenox® (enoxaparin sodium injection) confers any beneﬁt over UFH. The ASSENT-3 study gave researchers reason to believe that STEMI patients receiving ﬁbrinolysis might derive some beneﬁt from Lovenox over UFH.3 There are basic pharmacologic advantages of Lovenox over UFH, including a longer half-life, greater bioavailability, and more predictable activity. Lovenox can be dosed subcutaneously (SC) or given IV and monitoring of its effect generally is not necessary except in special circumstances. This is in contradistinction to the necessary ongoing monitoring with dose adjustment when using UFH. Activated partial thromboplastin time (APTT) is measured every 4 to 8 hours until the patient is stabilized, and then is checked daily thereafter. Can you describe the design of this study including the inclusion criteria and study protocol? This was a very well-designed, “double-blind, double-dummy,” international study with 20,506 patients who met the clinical and ECG criteria for STEMI. To be eligible, the clinical decision that the patient would be treated with ﬁbrinolytic therapy and not direct PCI had already been made. The choice of ﬁbrinolytic therapy was at the discretion of the treating physician. The dose used for UFH was a bolus of 60 U/kg (up to 4000 U), after which 12 U/kg (up to 1000 U)/hour were administered and patients were monitored to maintain APTT between 1.5 and 2.0 times control. These patients stayed on heparin for a minimum of 48 hours. Dosing of Lovenox was dependent upon both age and renal status; patients younger than 75 received a 30-mg weight-independent bolus, then 10 to 15 minutes later received 1 mg/kg of Lovenox SC. The SC dose was repeated every 12 hours throughout their hospitalization. Patients 75 years or older did not get the bolus, and the SC dose was adjusted to .75 mg/kg, again every 12 hours. Patients with creatinine clearance <30 mL/min received only 1 daily dose of Lovenox instead of two. 4

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - September 2008

Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.