CLINICIAN INTERVIEW RECOGNIZING ACS AND STRATIFYING RISK IN PRIMARY CARE. An interview with A. Michael Lincoff, MD, and Eric R. Bates, MD, FACC, FAHA

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1 RECOGNIZING ACS AND STRATIFYING RISK IN PRIMARY CARE An interview with A. Michael Lincoff, MD, and Eric R. Bates, MD, FACC, FAHA Dr Lincoff is an interventional cardiologist and the Vice Chairman for Research at the Cleveland Clinic Heart and Vascular Institute, and a Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio. He also serves as the Director of the Cleveland Clinic Coordinating Center for Clinical Research (C5Research), an organization devoted to clinical trials of new therapies to address cardiovascular disease. Dr Lincoff received his medical degree from Johns Hopkins University School of Medicine, completed an internship and residency at Beth Israel Deaconess Medical Center at the Harvard Medical School in Boston, Massachusetts,, and received training in cardiovascular medicine and interventional cardiology through fellowships with the University of Michigan Medical Center in Ann Arbor, Michigan, and the Cleveland Clinic. He is board certified in internal medicine, cardiovascular disease, and interventional cardiology. Dr Lincoff s clinical and research interests include coronary angioplasty and restenosis, acute coronary syndrome (ACS), acute myocardial infarction (MI), and the development of new antithrombotic therapies for use during coronary intervention. Dr Lincoff has served as a principal investigator for more than 15 clinical studies that researched new therapies to treat acute MI, manage unstable angina, or reduce complications of coronary revascularization. He is a member of the Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration, a Fellow in the American College of Cardiology, and a Fellow in the European Society of Cardiology. Dr Bates is Professor of Internal Medicine at the University of Michigan, Ann Arbor, specializing in cardiovascular disease. Dr Bates received his medical degree from the University of Michigan Medical School and completed his internship, residency, and fellowship in cardiology with the University of Michigan Health System. He is board certified in internal medicine, cardiovascular diseases, and interventional cardiology. Dr Bates serves as the chair of the American College of Cardiology (ACC) Ethics and Discipline Committee and is a member of the ACC/American Heart Association s writing committee to revise the 1999 guidelines for acute MI. He also serves as a member of the American Board of Internal Medicine Interventional Cardiology Test Committee. Dr Bates has served on the steering committees of numerous multicenter clinical trials. His major clinical interests include acute MI, ACS, and coronary artery disease. His research time is devoted to the progress of fibrinolytic and catheterbased reperfusion therapy for acute MI and cardiogenic shock, antiplatelet and anticoagulant therapy for coronary thrombosis, and coronary artery revascularization. A senior clinical editor for Johns Hopkins Advanced Studies in Medicine (JHASiM) interviewed Dr Lincoff and Dr Bates to provide readers with insight into the current issues facing primary care physicians who encounter patients at risk for ACS in daily practice. JHASiM: Could you suggest any specific tools or strategies for primary care physicians (PCP) to best identify patients who are at risk for acute coronary syndrome (ACS) and require additional follow-up? Dr Bates: The first thing that PCPs should begin with is a review of the patient s medical history. It is also important to emphasize the potential difference in symptoms and diagnosis based on specific demographic factors, such as the patient s gender or socioeconomic background. Differential diagnosis is critical, because chest pain could be consistent with approximately 20 different diagnoses, with possible causative factors varying from acid reflux, the flu, or depression 546 Vol. 7, No. 17 n December 2007

2 to pulmonary embolism, to name a few. PCPs should be comfortable taking a chest pain history and differentiating ischemic chest discomfort from nonischemic chest discomfort in routine practice. Dr Lincoff: When patients are seen in the emergency department (ED) or urgent care setting or in the office setting, for that matter clinicians should first assess the likelihood that the patient has coronary disease and whether the pain that they are experiencing is consistent with coronary or noncoronary chest pain. Symptoms on exertion in particular would be consistent with coronary chest pain, especially if accompanied by other symptoms, such as fatigue or shortness of breath. Chest pain that is nonischemic in nature would more likely be associated with pain that is reproduced by pressing on the chest or chest pain that occurs on rest but not exertion. On the other hand, exertional chest pain that has progressed to pain at rest is worrisome and consistent with ischemia. Also, chest pain in patients with a history of coronary disease, diabetes, or vascular disease should be highly suspect as ischemic pain. PRACTICE RECOMMENDATIONS FOR ACS The ACC/AHA guidelines for the management of UA/NSTEMI emphasize that primary care physicians should evaluate all patients for major cardiovascular risk factors at intervals of 3 to 5 years. Those with suspected ischemic pain should not be evaluated over the phone, but should be immediately referred to a facility with the ability to administer a 12-lead ECG to arrive at a more accurate diagnosis. Early risk stratification is also recommended in all patients presenting with suspected ACS. Patients with suspected ACS, despite normal ECG or biomarkers, should be referred for follow-up evaluations that include a repeat ECG, repeat biomarkers analysis, and stress test to provoke ischemia. Low-risk patients referred for outpatient stress testing should receive precautionary aspirin, sublingual nitroglycerin, and a β blocker while awaiting results of the stress test. Patients with definite ACS who experience ongoing ischemia, positive biomarkers, ST-segment elevations or deep T-wave inversions on ECG, hemodynamic abnormalities, or a positive stress test should be admitted to the hospital setting for further management. Source: Anderson JL, Adams CD, Antman EM, et al. J Am Coll Cardiol. 2007;50:e1-e157. Web site: Strength of Evidence: A panel of experts in the prevention, detection, and management of cardiovascular disease developed the ACC/AHA guidelines for the management of UA/NSTEMI. The recommendations for UA/NSTE- MI discussed above are all Class I recommendations that have a high potential for benefit and low potential for risk based on the available clinical evidence. JHASiM: If a patient does present with suspected ischemia, how should clinicians proceed with follow-up in the office setting? Dr Bates: An electrocardiogram (ECG) would be the most important next step in evaluating the patient, and most clinicians have the ability to perform an ECG in their office. Also, clinicians should consider blood testing for important biomarkers, including troponin, creatinine kinase MB, and brain natriuretic peptide as well as glucose, electrolytes, creatinine, low-density lipoprotein cholesterol, and white blood cell count to further support or rule out an ischemia diagnosis. Dr Lincoff: Careful examination is also important. For example, if the initial examination reveals signs of other cardiac conditions, such as heart failure or arrhythmia, this indicates that ischemia is more likely the cause of symptoms and that the patient may be at high risk for complications. Also, a normal ECG would not necessarily rule out ischemia, but a markedly abnormal ECG could support a diagnosis of ischemia. A physical examination and ECG are insensitive in detecting ischemia, but both are relatively specific when findings are abnormal. Going back to medical history, we should still stress the importance of traditional risk factors. The available research suggests that up to 80% of the predictive value for the development of atherosclerotic heart disease is linked to major traditional risk factors, including diabetes, hypertension, dyslipidemia, smoking, and a family history of heart disease. JHASiM: In patients who do present in primary care with ACS, which medications should be prescribed prior to further care in the hospital setting? Dr Bates: This may seem obvious, but it is still critical to emphasize the importance of aspirin in patients Johns Hopkins Advanced Studies in Medicine n 547

3 with suspected or established coronary disease. Some patients with established disease neglect to continue on aspirin, thinking that their more expensive prescription medications are sufficient to protect against future events. Aspirin is the most important intervention that we have, and it should be routinely used in these patients. Sublingual nitroglycerin and a β blocker also are warranted. Dr Lincoff: For a patient in whom an ACS seems likely, early administration of clopidogrel is recommended. This is still a point of some contention, as cardiac surgeons may be reluctant to operate for several days after a clopidogrel loading dose because of concerns regarding excess bleeding. In most cases, though, the likelihood that a patient presenting to primary care would require urgent surgical intervention is low, therefore, clopidogrel is probably safe in these patients. Also, there have been limited data to suggest that acute treatment with a statin may improve outcomes in patients with ACS undergoing percutaneous coronary intervention (PCI) because of immediate stabilization of the plaque with the statin. JHASiM: Could you describe the most important features of any standard algorithms or care pathways to improve early recognition of ACS? Dr Bates: The most important aspects of protocols and care pathways emphasize prompt care. First of all, many pathways now require that patients presenting with chest pain are seen and treated within 30 minutes of arrival. The majority of protocols also stress that patients with chest pain should receive an ECG within 10 minutes of arrival and that a physician should promptly evaluate the findings. Under new care pathways, the ED is now often responsible for delivering essential medications, such as aspirin, clopidogrel, unfractionated heparin or enoxaparin, nitroglycerin, and perhaps β blockers. In ST-segment elevation myocardial infarction (STEMI), these medications prepare the patient for prompt PCI. In non ST-segment elevation myocardial infarction (NSTEMI), these medications stabilize the patient and prepare the patient for later intervention if the clinician determines that the patient is at high risk of ischemic complications. It is also important to note a third pathway into which the bulk of patients may fall, in which they are admitted overnight to receive further diagnostics, including blood tests, repeat ECGs, and a stress test, to rule out ACS. In general, PCPs should be aware of the most recent American College of Cardiology/American Heart Association guidelines for the evaluation and management of patients with suspected ACS (Figure), 1 thus they are aware of the best practices governing the care of these patients from diagnosis through hospital discharge. Dr Lincoff: Because ACS encompasses both STEMI and NSTEMI, the primary strategy should be a prompt ECG to arrive at the most likely diagnosis, certainly within 10 minutes of arrival with chest pain. Most facilities have a protocol to deliver prompt PCI, within 90 minutes or less, if the patient is diagnosed with STEMI. Prompt PCI in STEMI has been adopted as a quality-of-care indicator for many healthcare payers, including Medicare, therefore hospitals are highly motivated to improve these times. Strategies, such as having ED physicians activate the catheterization laboratory, requiring interventional staff to arrive within 30 minutes of paging, and having emergency medical services staff transmit ECGs before hospital arrival, have all improved the time from presentation to PCI. JHASiM: Could you discuss some risk stratification tools used in ACS? Dr Bates: The Thrombolysis in Myocardial Infarction (TIMI) risk score (Table) 2 and the Global Registry of Acute Coronary Events (GRACE) risk calculator 3 are both useful guides for risk stratification and highlight factors that are easy to track in daily practice. After taking a medical history, performing a physical examination and an ECG, and ordering blood testing for biomarkers, risk stratification would be an important addition to providing a comprehensive evaluation in patients with suspected ACS. JHASiM: Does ACS care vary substantially by hospital? If so, should PCPs be aware of these differences and direct their patients accordingly? Dr Lincoff: I think that one of the advantages of having protocol-driven management in ACS is that the care delivered should be independent of the physician s specialty. Patients who have a fairly high likelihood of ACS should be managed with either prewritten orders or a treatment protocol that stresses the use of aspirin, clopidogrel, β blockers, and an antithrombotic (eg, heparin, low-molecular-weight heparin, bivalirudin, or fondaparinux), as well as a glycoprotein IIb/IIIa inhibitor in some patients. The 548 Vol. 7, No. 17 n December 2007

4 Figure. ACC/AHA Guidelines Algorithm for the Evaluation and Management of Patients with Suspected ACS To facilitate interpretation of this algorithm and a more detailed discussion in the text, each box is assigned a letter code that reflects its level in the algorithm and a number that is allocated from left to right across the diagram on a given level. ACC/AHA = American College of Cardiology/American Heart Association; ACS = acute coronary syndrome; ECG = electrocardiogram; LV = left ventricular. Reprinted with permission from Anderson et al. J Am Coll Cardiol. 2007;50:e1-e protocol should emphasize correct dosing, as dosing errors have been associated with a higher risk of bleeding events and poor outcomes. Often, clinicians do not take underlying comorbidities into account that could affect dosing requirements. Clinicians should be particularly alert to the fact that mild renal insufficiency is common in older patients, which could impact their ability to metabolize these drugs and confer a higher bleeding risk. Dr Bates: Although capabilities differ between hospitals, there should be a standard of care across all health systems to deliver basic evidence-based services, including risk stratification and proper medical support, to all patients diagnosed with ACS. JHASiM: How do facilities that do not have PCI capabilities coordinate with other specialty centers to provide prompt care for patients requiring intervention? Dr Lincoff: Many hospitals without PCI capability establish hub-and-spoke relationships with centers that perform coronary interventional procedures, allowing for expedited transfer. This works well from both perspectives, because the receiving hospital knows how the patient was managed before arrival, and the referring hospital has an established protocol of one center to which high-risk patients are sent. This could apply to patients with STEMI and high-risk patients with NSTEMI, such Johns Hopkins Advanced Studies in Medicine n 549

5 as those with ongoing chest discomfort, arrhythmia, or heart failure. Dr Bates: Again, the ability to stratify patients by risk in primary care, with tools such as the TIMI risk score and GRACE risk calculator, is critical so that high-risk individuals are promptly referred to centers with PCI capability, when possible. Table.The TIMI Risk Score for Patients with Non ST-Elevation ACS A. Scoring System Points Patient History Age 65 y 1 3 risk factors for CAD (history, hypertension, 1 hypercholesterolemia, overweight/obesity, and current smoker) Known CAD (stenosis 50%) 1 Aspirin use in the past 7 d 1 Clinical Presentation Recent ( 24 h) severe angina 1 Elevated cardiac markers 1 ST deviation of 0.5 mm on ECG 1 B. Risk of Cardiac Events (%) by TIMI Score* Risk of All-Cause Risk of All-Cause Mortality, MI, or Score Mortality or MI Urgent Revascularization 0/ / *Based on the TIMI 11b trial. ACS = acute coronary syndrome; CAD = coronary artery disease; ECG = electrocardiogram; MI = myocardial infarction; TIMI = Thrombolysis in Myocardial Infarction. Adapted with permission from Antman et al. JAMA. 2000;284: JHASiM: What are the major points that should be communicated to the PCP who is likely to see patients at risk for ACS in daily practice? Dr Lincoff: The key messages can be summed up in 4 major points. First of all, patients should be properly assessed to determine the likelihood that symptoms are a result of cardiac disease. If it is suspected cardiac disease, then an initial discrimination between STEMI (high risk) or NSTEMI (lower risk) should be made so that the individual receives prompt care. Once a patient is triaged to the appropriate treatment center, initial medical care should be delivered according to a standard protocol. Finally, patients with STEMI or high-risk NSTEMI should receive prompt intervention with PCI. Dr Bates: The importance of aspirin in patients with suspected ACS, as well as those with established coronary disease, should be emphasized again. Even if a patient does not seem to be in immediate danger, those presenting with suspicious chest pain should also be referred for a stress test, either immediately or within the period of 1 or 2 days. REFERENCES 1. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST- Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1-e Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-st elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284: Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163: Vol. 7, No. 17 n December 2007

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