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ACC/AHA 2007 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 Circulation. 2007;116;e148-e304 J. Am. Coll. Cardiol. 2007;50;652-726
Class I   Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Class IIa   Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class IIb   Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment  MAY BE CONSIDERED  Class III   Risk ≥ Benefit No additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level A:  Recommendation based on evidence from multiple randomized trials or meta-analyses  Multiple (3-5) population risk strata evaluated; General consistency of direction and magnitude of effect Level B:  Recommendation based on evidence from a single randomized trial or non-randomized studies  Limited (2-3) population risk strata evaluated Level C:  Recommendation based on expert opinion, case studies, or standard-of-care  Very limited (1-2) population risk strata evaluated should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established  is not recommended is not indicated should not is not useful/effective/beneficial may be harmful
Overview of Acute Coronary Syndromes (ACS)
Hospitalizations in the U.S. Due to ACS Acute Coronary Syndromes* 1.57 Million  Hospital Admissions - ACS UA/NSTEMI † STEMI 1.24 million   Admissions per year 0.33 million   Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
Initial Evaluation and Management of UA/NSTEMI
SYMPTOMS SUGGESTIVE OF ACS Noncardiac Diagnosis Chronic Stable Angina Possible ACS Definite ACS Treatment as indicated by alternative diagnosis ACC/AHA Chronic Stable Angina Guidelines No ST-Elevation ST-Elevation Nondiagnostic ECG Normal initial serum cardiac biomarkers ST and/or T wave changes Ongoing pain Positive cardiac biomarkers Hemodynamic abnormalities Evaluate for reperfusion therapy ACC/AHA STEMI Guidelines Observe ≥  12 h from symptom onset  No recurrent pain; negative follow-up studies Recurrent ischemic pain or positive follow-up studies Diagnosis of ACS confirmed Stress study to provoke ischemia Consider evaluation of LV function if ischemia is present (tests may be performed either prior to discharge or as outpatient) Negative Potential diagnoses: nonischemic discomfort; low-risk ACS Arrangements for outpatient follow-up Positive Diagnosis of ACS confirmed or highly likely Admit to hospital Manage via acute ischemia pathway Algorithm for evaluation and management of patients suspected of having ACS.  Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157, Figure 2.
Clinical Assessment Patients with  symptoms of ACS  (chest discomfort with or without radiation to the arm, back, neck, jaw, or epigastrium; SOB; weakness; diaphoresis; nausea; lightheadedness) should be instructed to call 911 and  should be transported to the hospital by ambulance  rather than by friends or relatives I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
Identification of ACS Patients in the ED Patients with the following symptoms and signs require  immediate assessment by the triage nurse  for the initiation of the ACS protocol: Chest pain or severe epigastric pain, non-traumatic in origin, with components typical of myocardial ischemia or MI: Central/substernal compression or crushing chest pain Pressure, tightness, heaviness, cramping, burning, aching sensation Unexplained indigestion, belching, epigastric pain Radiating pain in neck, jaw, shoulders, back, or 1 or both arms Associated dyspnea Associated nausea/vomiting Associated diaphoresis If these symptoms are present, obtain stat ECG Adapted from the National Heart Attack Alert Program. Emergency Department: rapid identification and treatment of patients with acute myocardial infarction. US Department of Health and Human Services. US Public Health Service. National Institutes of Health. National Heart, Lung and Blood Institute; September 1993; NIH Publication No. 93-3278. Also see Table 2 of  Anderson JL, et al.  J Am Coll Cardiol.  2007;50:e1-e157.
Clinical Assessment Health care providers should instruct patients with suspected ACS for whom NTG has been prescribed previously to take not more than 1 dose of NTG sublingually in response to chest discomfort/pain . If chest discomfort/pain is unimproved or is worsening 5 min after 1 NTG dose , it is recommended that the patient or family  call 911  immediately to access EMS before taking additional NTG.  In patients with chronic stable angina, if symptoms are significantly improved by 1 dose of NTG, it is appropriate to instruct the patient or family to repeat NTG every 5 min for a maximum of 3 doses and call 911 if symptoms have not resolved completely. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III c New 1 dose NTG
Has the patient been previously prescribed NTG? No Is Chest Discomfort/Pain Unimproved or Worsening 5 Minutes After It Starts ? Yes No CALL 9-1-1 IMMEDIATELY Follow 9-1-1 instructions  [Pts may receive instructions to chew ASA  (162-325 mg)* if not contraindicated or may receive ASA* en route to the hospital] Take  ONE NTG Dose  Sublingually Is Chest Discomfort/Pain Unimproved or Worsening 5 Minutes After Taking ONE NTG Dose Sublingually? Yes Yes No For pts with CSA, if sx are significantly improved after ONE NTG, repeat NTG every 5 min for a total of 3 doses and call 9-1-1 if sx have not totally resolved. Notify Physician Patient experiences chest pain/discomfort *Although some trials have used enteric-coated ASA for initial dosing, more rapid buccal absorption occurs with non–enteric-coated formulations. Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157, Figure 3. CSA = chronic stable angina.
Clinical Assessment It is reasonable for health care providers and 911 dispatchers to advise patients without a history of ASA allergy who have symptoms of ACS to chew  ASA  (162 to 325 mg) while awaiting arrival of prehospital EMS providers. Although some trials have used enteric-coated ASA for initial dosing, more rapid buccal absorption occurs with  non–enteric-coated  formulations. It is reasonable for health care providers and 911 dispatchers to advise patients who tolerate NTG to  repeat NTG every 5 min for a maximum of 3 doses  while awaiting ambulance arrival. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New New
Early Risk Stratification A  12-lead ECG  should be performed and shown to an experienced emergency physician  as soon as possible after ED arrival, with a goal of within 10 min of ED arrival  for all patients with chest discomfort or other symptoms suggestive of ACS. If initial ECG is not diagnostic but patient remains symptomatic and there is high clinical suspicion for ACS,  serial ECGs, initially at 15- to 30-min intervals,  should be performed to detect the potential for development of ST-segment elevation or depression. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
Early Risk Stratification Use of risk-stratification models, such as the  TIMI or GRACE risk score or PURSUIT risk model , can be useful to assist in decision making with regard to treatment options in patients with suspected ACS.  It is reasonable to  remeasure positive biomarkers at 6- to 8-h intervals 2 to 3 times or until levels have peaked , as an index of infarct size and dynamics of necrosis. GRACE = Global Registry of Acute Coronary Events; PURSUIT = Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy; TIMI = Thrombolysis In Myocardial Infarction.  I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New New
Variables Used in the TIMI Risk Score The TIMI risk score is determined by the sum of the presence of the above 7 variables at admission. 1 point is given for each variable. Primary coronary stenosis of 50% or more remained relatively insensitive to missing information and remained a significant predictor of events. Antman EM, et al.  JAMA  2000;284:835–42. TIMI = Thrombolysis in Myocardial Infarction. Age ≥ 65 years At least 3 risk factors for CAD Prior coronary stenosis of ≥ 50% ST-segment deviation on ECG At least 2 anginal events in prior 24 hours Use of aspirin in prior 7 days Elevated serum cardiac biomarkers
TIMI Risk Score Reprinted with permission from Antman EM, et al.  JAMA  2000;284:835–42. Copyright © 2000, American Medical Association. All Rights reserved. The TIMI risk calculator is available at www.timi.org.  Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157, Table 8. TIMI = Thrombolysis in Myocardial Infarction. TIMI Risk Score All-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 Days After Randomization % 0-1 4.7 2 8.3 3 13.2 4 19.9 5 26.2 6-7 40.9
GRACE Risk Score The sum of scores is applied to a reference monogram to determine the corresponding all-cause mortality from hospital discharge to 6 months. Eagle KA, et al.  JAMA  2004;291:2727–33.  The GRACE clinical application tool can be found at www.outcomes-umassmed.org/grace. Also see Figure 4 in Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157. GRACE = Global Registry of Acute Coronary Events. Variable Odds ratio Older age 1.7 per 10 y Killip class 2.0 per class Systolic BP 1.4 per 20 mm Hg ↑ ST-segment deviation 2.4 Cardiac arrest during presentation 4.3 Serum creatinine level 1.2 per 1-mg/dL ↑ Positive initial cardiac biomarkers 1.6 Heart rate 1.3 per 30-beat/min ↑
Early Risk Stratification For patients who  present within 6 h  of the onset of symptoms consistent with ACS, assessment of an early marker of cardiac injury (e.g.,  myoglobin ) in conjunction with a late marker (e.g., troponin) may be considered.  For patients who present within 6 h of symptoms suggestive of ACS, a  2-h delta CK-MB  mass in conjunction with 2-h delta troponin may be considered.  I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New IIa->IIb
Early Risk Stratification For patients who  present within 6 h  of symptoms suggestive of ACS,  myoglobin  in conjunction with CK-MB mass or troponin when measured  at baseline and 90 min  may be considered.  B-type natriuretic peptide (BNP)  or NT-pro-BNP may be considered to supplement assessment of global risk in patients with suspected ACS.  I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New New
Early Risk Stratification Total CK (without MB), AST, SGOT, alanine transaminase, beta-hydroxybutyric dehydrogenase, and/or LDH should  not  be utilized as primary tests for the detection of myocardial injury in patients with chest discomfort suggestive of ACS. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
Immediate Management The history, physical examination, 12-lead ECG, and initial cardiac biomarker tests should be integrated to assign patients with chest pain into one of 4 categories:  non-cardiac diagnosis chronic stable angina possible ACS definite ACS I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
Immediate Management Patients with  probable or possible ACS  but whose initial 12-lead ECG and cardiac biomarker levels are normal should be observed in a facility with  cardiac monitoring  (e.g.,  chest pain unit  or  hospital telemetry ward ), and repeat ECG (or continuous 12-lead ECG monitoring) and repeat cardiac biomarker measurement(s) should be obtained at predetermined, specified time intervals*.  *See Section 2.2.8 in Anderson JA, et al.  J Am Coll Cardiol  2007:50:e1-e157. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B Major Change
Immediate Management In low-risk patients who are referred for outpatient stress testing (see previous slide), precautionary appropriate pharmacotherapy (e.g., ASA, sublingual NTG, and/or beta blockers) should be given while awaiting results of the stress test. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
Immediate Management In patients with suspected ACS with a low or intermediate probability of CAD, in whom the follow-up 12-lead ECG and cardiac biomarkers measurements are normal, performance of a noninvasive coronary imaging test (i.e.,  coronary CT angiography ) is reasonable as an alternative to stress testing. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
Early Hospital Care
Anti-Ischemic Therapy Oral beta-blocker therapy  should be initiated within the first 24 h for patients who do not have 1 or more of the following: signs of HF evidence of low-output state increased risk* for cardiogenic shock other relative contraindications to beta blockade PR interval greater than 0.24 s second or third degree heart block active asthma, or reactive airway disease *Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age greater than 70 years, systolic blood pressure less than 120 mmHg, sinus tachycardia greater than 110 or heart rate less than 60, increased time since onset of symptoms of UA/NSTEMI. Chen ZM, et al.  Lancet  2005;366:1622–32. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B Major Change
Anti-Ischemic Therapy ACE inhibitor  should be administered orally within the first 24 h to UA/NSTEMI patients with  pulmonary congestion or LVEF ≤ 40%, in the absence of hypotension  (SBP < 100 mmHg or < 30 mmHg below baseline) or known contraindications to that class of medications.  Angiotensin receptor blocker should be administered to UA/NSTEMI patients who are intolerant of ACE inhibitors and have either clinical or radiological signs of HF or LVEF ≤ 40%. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A Major Change New
Anti-Ischemic Therapy It is reasonable to administer supplemental  oxygen  to all patients with UA/NSTEMI during the first 6 h after presentation.  In the absence of contradictions to its use, it is reasonable to administer  morphine  intravenously to UA/NSTEMI patients if there is  uncontrolled ischemic chest discomfort  despite NTG, provided that additional therapy is used to manage the underlying ischemia. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New I -> IIa
Anti-Ischemic Therapy It is reasonable to administer  intravenous beta blockers  at the time of presentation for  hypertension  to UA/NSTEMI patients who do not have 1 or more of the following:  signs of HF evidence of a low-output state increased risk* for cardiogenic shock other relative contraindications to beta blockade PR interval greater than 0.24 s second or third degree heart block active asthma, or reactive airway disease *Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age greater than 70 years, systolic blood pressure less than 120 mmHg, sinus tachycardia greater than 110 or heart rate less than 60, increased time since onset of symptoms of UA/NSTEMI. Chen ZM, et al.  Lancet  2005;366:1622–32. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I -> IIa
Anti-Ischemic Therapy IABP  counterpulsation is reasonable in UA/NSTEMI patients for severe ischemia that is continuing or recurs frequently despite intensive medical therapy, for  hemodynamic instability  in patients before or after coronary angiography, and for mechanical complications of MI. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
Anti-Ischemic Therapy Nitrates  should  not  be administered to UA/NSTEMI patients with SBP < 90 mmHg or ≥ 30 mmHg below baseline, severe bradycardia (< 50 bpm), tachycardia (> 100 bpm) in the absence of symptomatic HF, or right ventricular infarction. Nitroglycerin  should  not  be administered to patients with UA/NSTEMI who had received a phosphodiesterase inhibitor for erectile dysfunction within 24 h of  sildenafil (Viagra) or 48 h of  tadalafil (Calis)  use. The suitable time for the administration of nitrates after  vardenafil (Levitra)  has not been determined. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New Drugs
Anti-Ischemic Therapy NSAID  (except for ASA), whether nonselective or COX-2–selective agents, should not be administered during hospitalization for UA/NSTEMI because of the increased risks of mortality, reinfarction, hypertension, HF, and myocardial rupture associated with their use. The selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk. An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk to the patient (Antman EM, et al. Use of nonsteroidal antiinflammatory drugs. An update for clinicians. A scientific statement from the American Heart Association.  Circulation  2007;115:1634–42. Further discussion can be found in Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157 and in the Secondary Prevention Section of this slide set. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
Antiplatelet Therapy Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients not known to be intolerant of that medication.  (Box A) Clopidogrel (loading dose followed by daily maintenance dose)* should be administered to UA/NSTEMI patients who are unable to take ASA because of hypersensitivity or major GI intolerance.  (Box A) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A LD added
Select Management Strategy:  Initial Invasive Versus  Initial Conservative Strategy Major Changes New Trial Data
Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy Invasive Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy Elevated cardiac biomarkers (TnT or TnI) New/presumably new ST-segment depression Signs/symptoms of heart failure or new/worsening mitral regurgitation High-risk findings from noninvasive testing Hemodynamic instability Sustained ventricular tachycardia PCI within 6 months Prior CABG High risk score (e.g., TIMI, GRACE) Reduced left ventricular function (LVEF < 40%) Conservative Low risk score (e.g., TIMI, GRACE) Patient/physician presence in the absence of high-risk features
Initial Conservative Versus Initial Invasive Strategies In initially stabilized patients, an initially conservative (i.e., a selectively invasive) strategy may be considered as a treatment strategy for  UA/ NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events including those who are troponin positive.  An invasive strategy may be reasonable in patients with chronic renal insufficiency. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New New
Initial Invasive Strategy  Major Changes New Drugs Longer Duration of Rx Revised Algorithm
Algorithm for Patients with UA/NSTEMI Managed by an Initial Invasive Strategy Proceed to Diagnostic Angiography ASA (Class I, LOE: A) Clopidogrel if ASA intolerant (Class I, LOE: A) Diagnosis of UA/NSTEMI is Likely or Definite Invasive Strategy Init ACT (Class I, LOE: A) Acceptable options: enoxaparin or UFH  (Class I, LOE: A)  bivalirudin or fondaparinux (Class I, LOE: B)  Select Management Strategy Proceed with an Initial Conservative Strategy  Anderson JL, et al.  J Am Coll Cardiol . 2007;50:e1-e157, Figure 7. ACT = anticoagulation therapy; LOE = level of evidence. A B B1 B2 Prior to Angiography Init at least one (Class I, LOE: A) or  both (Class IIa, LOE: B) of the following: Clopidogrel IV GP IIb/IIIa inhibitor Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include: Delay to Angiography High Risk Features Early recurrent ischemic discomfort
Initial Invasive Strategy:  Antiplatelet Therapy For UA/NSTEMI patients in whom an initial invasive strategy is selected, antiplatelet therapy in addition to  ASA  should be initiated before diagnostic angiography (upstream) with either  clopidogrel  (loading dose followed by daily maintenance dose)*  or  an  IV GP IIb/IIIa inhibitor .  (Box B2) Abciximab (ReoPro) as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide (Integrilin) or tirofiban (Aggrastat) is the preferred choice of GP IIb/IIIa inhibitor.† *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established; †Factors favoring administration of both clopidogrel and a GP IIb/IIIa inhibitor include: delay to angiography, high-risk features, and early ischemic discomfort. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
Initial Invasive Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to initiate antiplatelet therapy with both  clopidogrel  (loading dose followed by daily maintenance dose)*  and  an intravenous  GP IIb/IIIa inhibitor .   (Box B2) Abciximab as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide or tirofiban is the preferred choice of GP IIb/IIIa inhibitor.†  *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established; †Factors favoring administration of both clopidogrel and a GP IIb/IIIa inhibitor include: delay to angiography, high-risk features, and early ischemic discomfort. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
Initial Invasive Strategy: Anticoagulant Therapy Anticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients as soon as possible after presentation. For patients in whom an invasive strategy is selected, regimens with established efficacy at a  Level of Evidence: A  include  enoxaparin   (Clexane ® )  and unfractionated  heparin  (UFH)  (Box B1),  and those with established efficacy at a  Level of Evidence: B  include  bivalirudin (Angiomax ® )  and  fondaparinux (Arixtra ® ) (Box B1). I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A New Drugs
Initial Conservative Strategy  Major Changes New Drugs Longer Duration of Rx Revised Algorithm
Init clopidogrel (Class I, LOE: A)  Consider adding IV eptifibatide or tirofiban (Class IIb, LOE: B)  Conservative Strategy Init ACT (Class I, LOE: A):  Acceptable options: enoxaparin or UFH (Class I, LOE: A) or fondaparinux (Class I, LOE: B),   but enoxaparin or fondaparinux are preferable (Class IIa, LOE: B) Select Management Strategy ASA (Class I, LOE: A) Clopidogrel if ASA intolerant (Class I, LOE: A) Diagnosis of UA/NSTEMI is Likely or Definite Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy Proceed with Invasive Strategy (Continued) Anderson JL, et al.  J Am Coll Cardiol . 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy;  LOE = level of evidence. C2 C1 A
Any subsequent events necessitating angiography? EF greater  than 40% Evaluate LVEF Low Risk Cont ASA (Class I, LOE A)  Cont clopidogrel (Class I, LOE A) and ideally up to 1 yr (Class I, LOE B) DC IV GP IIb/IIIa if started previously (Class I, LOE A)  DC ACT (Class I, LOE A)  (Class I, LOE: B) Proceed to Dx Angiography Yes EF  40% or less Stress Test (Class I, LOE: A) No Not Low Risk (Class IIa, LOE: B) Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy   (Continued) Anderson JL, et al.  J Am Coll Cardiol . 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy; LOE = level of evidence. (Class I, LOE: A) (Class IIa, LOE: B) O L M N K E-1 E-2 D   (Class I,  LOE: B) (Class I, LOE: A)
Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected,  clopidogrel  (loading dose followed by daily maintenance dose)* should be added to  ASA  and  anticoagulant therapy as soon as possible after admission  and administered for at least 1 month  (Level of Evidence: A)  and ideally up to 1 year.  (Level of Evidence: B)  (Box C2) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative strategy is selected, if  recurrent symptoms/ischemia, HF, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed .  (Level of Evidence: A)  (Box D)  Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban;  Level of Evidence: A ) or clopidogrel (loading dose followed by daily maintenance dose;  Level of Evidence: A) * should be added to ASA and anticoagulant therapy before diagnostic angiography (upstream).  (Level of Evidence: C) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. See recommendation for LOE I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.   (Box C2) Abciximab should not be administered to patients in whom PCI is not planned. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
Initial Conservative Strategy: Anticoagulant Therapy Anticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients  as soon as possible  after presentation. For patients in whom a conservative strategy is  selected, regimens using either enoxaparin* or  UFH  (Level of Evidence: A)  or fondaparinux  (Level  of Evidence: B)  have established efficacy.  (Box  C1)  In patients in whom a conservative strategy is  selected and who have an increased risk of  bleeding, fondaparinux is preferable.   (Box C1) B *Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A New Drugs
Initial Conservative Strategy: Anticoagulant Therapy For UA/NSTEMI patients in whom an initial conservative strategy is selected,  enoxaparin* or fondaparinux is preferable to UFH  as anticoagulant therapy, unless CABG is planned within 24 h. *Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
Initial Conservative Strategy: Additional Management Considerations For UA/NSTEMI patients in whom an initial conservative strategy is selected and no subsequent features appear that would  necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), a  stress test  should be performed.  (Box O) a. If, after stress testing, the patient is  classified as not at low risk, diagnostic  angiography should be performed.  (Box E1) This recommendation continues on the next slide. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
Initial Conservative Strategy: Additional Management Considerations b. If, after stress testing, the patient is classified as being at  low risk (Box E2) , the instructions noted below should be followed in preparation for discharge  (Box K) : Continue ASA indefinitely.  (Level of Evidence: A) Continue clopidogrel for at least 1 month  (Level of Evidence: A)  and ideally up to 1 year.  (Level of Evidence: B) Discontinue IV GP IIb/IIIa inhibitor  if started previously.  (Level of Evidence: A) Continue UFH for 48 h or administer enoxaparin or fondaparinux for the duration of hospitalization, up to 8 d, and then discontinue anticoagulant therapy.  (Level of Evidence: A) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
Initial Conservative Strategy: Additional Management Considerations For UA/NSTEMI patients in whom an initial conservative strategy is selected and in whom no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias),  LVEF  should be measured.   (Box L) If LVEF is ≤ 40%, it is reasonable to perform diagnostic angiography.   (Box M) If LVEF is > 40%, it is reasonable to perform a stress test.   (Box N) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
Cardiac cath CAD No Discharge from protocol Yes Left main disease Yes CABG No 1- or 2- Vessel Disease 3- or 2-vessel disease with proximal LAD involvement LV dysfunction or treated diabetes* No PCI or CABG Medial Therapy, PCI or CABG Yes CABG *There is conflicting information about these patients. Most consider CABG to be preferable to PCI.  Anderson JL, et al.  J Am Coll Cardiol  2007;50:e1–e157, Figure 20. Revascularization Strategy in UA/NSTEMI
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) At the time of preparation for hospital discharge, the patient’s need for treatment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach to treatment should be used for selection of treatments.  Pain relief should begin with acetaminophen, small doses of narcotics, or nonacetylated salicylates.  I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
NSAIDs It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, small doses of narcotics, or nonacetylated salicylates is insufficient.  I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
Stepped-Care Approach to Pharmacological Therapy for Musculoskeletal Symptoms With Known Cardiovascular Disease or Risk Factors for Ischemic Heart Disease *Addition of ASA may not be sufficient protection against thrombotic events.  Reproduced with permission from Antman EM, et al. Circulation 2007;115:1634–42.  PPI = proton-pump inhibitor. Acetaminophen, ASA, tramadol,  narcotic analgesics (short term) Nonacetylated salicylates Non COX-2 selective NSAIDs NSAIDs with some COX-2 selectivity COX-2 selective NSAIDs Select pts at low risk of thrombotic events Prescribe lowest dose required to control symptoms Add ASA 81 mg and PPI to pts at ↑ risk of thrombotic events* Regular monitoring for sustained hypertension (or worsening of prior BP control), edema, worsening renal function, or GI bleeding If these occur, consider reduction of the dose or discontinuation of the offending drug, a different drug, or alternative therapeutic modalities, as dictated by clinical circumstances New
ED Management Strategies: Guidelines at a Glance (See full text for indications and contraindications of listed elements; &quot;check&quot; mark = generally indicated; +/– = possibly indicated; – = generally not indicated.)

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ACC/AHA 2007 Guidelines for UA & NSTEMI

  • 1. ACC/AHA 2007 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 Circulation. 2007;116;e148-e304 J. Am. Coll. Cardiol. 2007;50;652-726
  • 2. Class I Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Class IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class IIb Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk ≥ Benefit No additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level A: Recommendation based on evidence from multiple randomized trials or meta-analyses Multiple (3-5) population risk strata evaluated; General consistency of direction and magnitude of effect Level B: Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated Level C: Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established is not recommended is not indicated should not is not useful/effective/beneficial may be harmful
  • 3. Overview of Acute Coronary Syndromes (ACS)
  • 4. Hospitalizations in the U.S. Due to ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI † STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
  • 5. Initial Evaluation and Management of UA/NSTEMI
  • 6. SYMPTOMS SUGGESTIVE OF ACS Noncardiac Diagnosis Chronic Stable Angina Possible ACS Definite ACS Treatment as indicated by alternative diagnosis ACC/AHA Chronic Stable Angina Guidelines No ST-Elevation ST-Elevation Nondiagnostic ECG Normal initial serum cardiac biomarkers ST and/or T wave changes Ongoing pain Positive cardiac biomarkers Hemodynamic abnormalities Evaluate for reperfusion therapy ACC/AHA STEMI Guidelines Observe ≥ 12 h from symptom onset No recurrent pain; negative follow-up studies Recurrent ischemic pain or positive follow-up studies Diagnosis of ACS confirmed Stress study to provoke ischemia Consider evaluation of LV function if ischemia is present (tests may be performed either prior to discharge or as outpatient) Negative Potential diagnoses: nonischemic discomfort; low-risk ACS Arrangements for outpatient follow-up Positive Diagnosis of ACS confirmed or highly likely Admit to hospital Manage via acute ischemia pathway Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2.
  • 7. Clinical Assessment Patients with symptoms of ACS (chest discomfort with or without radiation to the arm, back, neck, jaw, or epigastrium; SOB; weakness; diaphoresis; nausea; lightheadedness) should be instructed to call 911 and should be transported to the hospital by ambulance rather than by friends or relatives I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
  • 8. Identification of ACS Patients in the ED Patients with the following symptoms and signs require immediate assessment by the triage nurse for the initiation of the ACS protocol: Chest pain or severe epigastric pain, non-traumatic in origin, with components typical of myocardial ischemia or MI: Central/substernal compression or crushing chest pain Pressure, tightness, heaviness, cramping, burning, aching sensation Unexplained indigestion, belching, epigastric pain Radiating pain in neck, jaw, shoulders, back, or 1 or both arms Associated dyspnea Associated nausea/vomiting Associated diaphoresis If these symptoms are present, obtain stat ECG Adapted from the National Heart Attack Alert Program. Emergency Department: rapid identification and treatment of patients with acute myocardial infarction. US Department of Health and Human Services. US Public Health Service. National Institutes of Health. National Heart, Lung and Blood Institute; September 1993; NIH Publication No. 93-3278. Also see Table 2 of Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157.
  • 9. Clinical Assessment Health care providers should instruct patients with suspected ACS for whom NTG has been prescribed previously to take not more than 1 dose of NTG sublingually in response to chest discomfort/pain . If chest discomfort/pain is unimproved or is worsening 5 min after 1 NTG dose , it is recommended that the patient or family call 911 immediately to access EMS before taking additional NTG. In patients with chronic stable angina, if symptoms are significantly improved by 1 dose of NTG, it is appropriate to instruct the patient or family to repeat NTG every 5 min for a maximum of 3 doses and call 911 if symptoms have not resolved completely. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III c New 1 dose NTG
  • 10. Has the patient been previously prescribed NTG? No Is Chest Discomfort/Pain Unimproved or Worsening 5 Minutes After It Starts ? Yes No CALL 9-1-1 IMMEDIATELY Follow 9-1-1 instructions [Pts may receive instructions to chew ASA (162-325 mg)* if not contraindicated or may receive ASA* en route to the hospital] Take ONE NTG Dose Sublingually Is Chest Discomfort/Pain Unimproved or Worsening 5 Minutes After Taking ONE NTG Dose Sublingually? Yes Yes No For pts with CSA, if sx are significantly improved after ONE NTG, repeat NTG every 5 min for a total of 3 doses and call 9-1-1 if sx have not totally resolved. Notify Physician Patient experiences chest pain/discomfort *Although some trials have used enteric-coated ASA for initial dosing, more rapid buccal absorption occurs with non–enteric-coated formulations. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 3. CSA = chronic stable angina.
  • 11. Clinical Assessment It is reasonable for health care providers and 911 dispatchers to advise patients without a history of ASA allergy who have symptoms of ACS to chew ASA (162 to 325 mg) while awaiting arrival of prehospital EMS providers. Although some trials have used enteric-coated ASA for initial dosing, more rapid buccal absorption occurs with non–enteric-coated formulations. It is reasonable for health care providers and 911 dispatchers to advise patients who tolerate NTG to repeat NTG every 5 min for a maximum of 3 doses while awaiting ambulance arrival. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New New
  • 12. Early Risk Stratification A 12-lead ECG should be performed and shown to an experienced emergency physician as soon as possible after ED arrival, with a goal of within 10 min of ED arrival for all patients with chest discomfort or other symptoms suggestive of ACS. If initial ECG is not diagnostic but patient remains symptomatic and there is high clinical suspicion for ACS, serial ECGs, initially at 15- to 30-min intervals, should be performed to detect the potential for development of ST-segment elevation or depression. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
  • 13. Early Risk Stratification Use of risk-stratification models, such as the TIMI or GRACE risk score or PURSUIT risk model , can be useful to assist in decision making with regard to treatment options in patients with suspected ACS. It is reasonable to remeasure positive biomarkers at 6- to 8-h intervals 2 to 3 times or until levels have peaked , as an index of infarct size and dynamics of necrosis. GRACE = Global Registry of Acute Coronary Events; PURSUIT = Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy; TIMI = Thrombolysis In Myocardial Infarction. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New New
  • 14. Variables Used in the TIMI Risk Score The TIMI risk score is determined by the sum of the presence of the above 7 variables at admission. 1 point is given for each variable. Primary coronary stenosis of 50% or more remained relatively insensitive to missing information and remained a significant predictor of events. Antman EM, et al. JAMA 2000;284:835–42. TIMI = Thrombolysis in Myocardial Infarction. Age ≥ 65 years At least 3 risk factors for CAD Prior coronary stenosis of ≥ 50% ST-segment deviation on ECG At least 2 anginal events in prior 24 hours Use of aspirin in prior 7 days Elevated serum cardiac biomarkers
  • 15. TIMI Risk Score Reprinted with permission from Antman EM, et al. JAMA 2000;284:835–42. Copyright © 2000, American Medical Association. All Rights reserved. The TIMI risk calculator is available at www.timi.org. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Table 8. TIMI = Thrombolysis in Myocardial Infarction. TIMI Risk Score All-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 Days After Randomization % 0-1 4.7 2 8.3 3 13.2 4 19.9 5 26.2 6-7 40.9
  • 16. GRACE Risk Score The sum of scores is applied to a reference monogram to determine the corresponding all-cause mortality from hospital discharge to 6 months. Eagle KA, et al. JAMA 2004;291:2727–33. The GRACE clinical application tool can be found at www.outcomes-umassmed.org/grace. Also see Figure 4 in Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157. GRACE = Global Registry of Acute Coronary Events. Variable Odds ratio Older age 1.7 per 10 y Killip class 2.0 per class Systolic BP 1.4 per 20 mm Hg ↑ ST-segment deviation 2.4 Cardiac arrest during presentation 4.3 Serum creatinine level 1.2 per 1-mg/dL ↑ Positive initial cardiac biomarkers 1.6 Heart rate 1.3 per 30-beat/min ↑
  • 17. Early Risk Stratification For patients who present within 6 h of the onset of symptoms consistent with ACS, assessment of an early marker of cardiac injury (e.g., myoglobin ) in conjunction with a late marker (e.g., troponin) may be considered. For patients who present within 6 h of symptoms suggestive of ACS, a 2-h delta CK-MB mass in conjunction with 2-h delta troponin may be considered. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New IIa->IIb
  • 18. Early Risk Stratification For patients who present within 6 h of symptoms suggestive of ACS, myoglobin in conjunction with CK-MB mass or troponin when measured at baseline and 90 min may be considered. B-type natriuretic peptide (BNP) or NT-pro-BNP may be considered to supplement assessment of global risk in patients with suspected ACS. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New New
  • 19. Early Risk Stratification Total CK (without MB), AST, SGOT, alanine transaminase, beta-hydroxybutyric dehydrogenase, and/or LDH should not be utilized as primary tests for the detection of myocardial injury in patients with chest discomfort suggestive of ACS. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
  • 20. Immediate Management The history, physical examination, 12-lead ECG, and initial cardiac biomarker tests should be integrated to assign patients with chest pain into one of 4 categories: non-cardiac diagnosis chronic stable angina possible ACS definite ACS I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
  • 21. Immediate Management Patients with probable or possible ACS but whose initial 12-lead ECG and cardiac biomarker levels are normal should be observed in a facility with cardiac monitoring (e.g., chest pain unit or hospital telemetry ward ), and repeat ECG (or continuous 12-lead ECG monitoring) and repeat cardiac biomarker measurement(s) should be obtained at predetermined, specified time intervals*. *See Section 2.2.8 in Anderson JA, et al. J Am Coll Cardiol 2007:50:e1-e157. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B Major Change
  • 22. Immediate Management In low-risk patients who are referred for outpatient stress testing (see previous slide), precautionary appropriate pharmacotherapy (e.g., ASA, sublingual NTG, and/or beta blockers) should be given while awaiting results of the stress test. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
  • 23. Immediate Management In patients with suspected ACS with a low or intermediate probability of CAD, in whom the follow-up 12-lead ECG and cardiac biomarkers measurements are normal, performance of a noninvasive coronary imaging test (i.e., coronary CT angiography ) is reasonable as an alternative to stress testing. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New
  • 25. Anti-Ischemic Therapy Oral beta-blocker therapy should be initiated within the first 24 h for patients who do not have 1 or more of the following: signs of HF evidence of low-output state increased risk* for cardiogenic shock other relative contraindications to beta blockade PR interval greater than 0.24 s second or third degree heart block active asthma, or reactive airway disease *Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age greater than 70 years, systolic blood pressure less than 120 mmHg, sinus tachycardia greater than 110 or heart rate less than 60, increased time since onset of symptoms of UA/NSTEMI. Chen ZM, et al. Lancet 2005;366:1622–32. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B Major Change
  • 26. Anti-Ischemic Therapy ACE inhibitor should be administered orally within the first 24 h to UA/NSTEMI patients with pulmonary congestion or LVEF ≤ 40%, in the absence of hypotension (SBP < 100 mmHg or < 30 mmHg below baseline) or known contraindications to that class of medications. Angiotensin receptor blocker should be administered to UA/NSTEMI patients who are intolerant of ACE inhibitors and have either clinical or radiological signs of HF or LVEF ≤ 40%. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A Major Change New
  • 27. Anti-Ischemic Therapy It is reasonable to administer supplemental oxygen to all patients with UA/NSTEMI during the first 6 h after presentation. In the absence of contradictions to its use, it is reasonable to administer morphine intravenously to UA/NSTEMI patients if there is uncontrolled ischemic chest discomfort despite NTG, provided that additional therapy is used to manage the underlying ischemia. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B New I -> IIa
  • 28. Anti-Ischemic Therapy It is reasonable to administer intravenous beta blockers at the time of presentation for hypertension to UA/NSTEMI patients who do not have 1 or more of the following: signs of HF evidence of a low-output state increased risk* for cardiogenic shock other relative contraindications to beta blockade PR interval greater than 0.24 s second or third degree heart block active asthma, or reactive airway disease *Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age greater than 70 years, systolic blood pressure less than 120 mmHg, sinus tachycardia greater than 110 or heart rate less than 60, increased time since onset of symptoms of UA/NSTEMI. Chen ZM, et al. Lancet 2005;366:1622–32. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I -> IIa
  • 29. Anti-Ischemic Therapy IABP counterpulsation is reasonable in UA/NSTEMI patients for severe ischemia that is continuing or recurs frequently despite intensive medical therapy, for hemodynamic instability in patients before or after coronary angiography, and for mechanical complications of MI. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C
  • 30. Anti-Ischemic Therapy Nitrates should not be administered to UA/NSTEMI patients with SBP < 90 mmHg or ≥ 30 mmHg below baseline, severe bradycardia (< 50 bpm), tachycardia (> 100 bpm) in the absence of symptomatic HF, or right ventricular infarction. Nitroglycerin should not be administered to patients with UA/NSTEMI who had received a phosphodiesterase inhibitor for erectile dysfunction within 24 h of sildenafil (Viagra) or 48 h of tadalafil (Calis) use. The suitable time for the administration of nitrates after vardenafil (Levitra) has not been determined. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New Drugs
  • 31. Anti-Ischemic Therapy NSAID (except for ASA), whether nonselective or COX-2–selective agents, should not be administered during hospitalization for UA/NSTEMI because of the increased risks of mortality, reinfarction, hypertension, HF, and myocardial rupture associated with their use. The selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk. An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk to the patient (Antman EM, et al. Use of nonsteroidal antiinflammatory drugs. An update for clinicians. A scientific statement from the American Heart Association. Circulation 2007;115:1634–42. Further discussion can be found in Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157 and in the Secondary Prevention Section of this slide set. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
  • 32. Antiplatelet Therapy Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients not known to be intolerant of that medication. (Box A) Clopidogrel (loading dose followed by daily maintenance dose)* should be administered to UA/NSTEMI patients who are unable to take ASA because of hypersensitivity or major GI intolerance. (Box A) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A LD added
  • 33. Select Management Strategy: Initial Invasive Versus Initial Conservative Strategy Major Changes New Trial Data
  • 34. Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy Invasive Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy Elevated cardiac biomarkers (TnT or TnI) New/presumably new ST-segment depression Signs/symptoms of heart failure or new/worsening mitral regurgitation High-risk findings from noninvasive testing Hemodynamic instability Sustained ventricular tachycardia PCI within 6 months Prior CABG High risk score (e.g., TIMI, GRACE) Reduced left ventricular function (LVEF < 40%) Conservative Low risk score (e.g., TIMI, GRACE) Patient/physician presence in the absence of high-risk features
  • 35. Initial Conservative Versus Initial Invasive Strategies In initially stabilized patients, an initially conservative (i.e., a selectively invasive) strategy may be considered as a treatment strategy for UA/ NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events including those who are troponin positive. An invasive strategy may be reasonable in patients with chronic renal insufficiency. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New New
  • 36. Initial Invasive Strategy Major Changes New Drugs Longer Duration of Rx Revised Algorithm
  • 37. Algorithm for Patients with UA/NSTEMI Managed by an Initial Invasive Strategy Proceed to Diagnostic Angiography ASA (Class I, LOE: A) Clopidogrel if ASA intolerant (Class I, LOE: A) Diagnosis of UA/NSTEMI is Likely or Definite Invasive Strategy Init ACT (Class I, LOE: A) Acceptable options: enoxaparin or UFH (Class I, LOE: A) bivalirudin or fondaparinux (Class I, LOE: B) Select Management Strategy Proceed with an Initial Conservative Strategy Anderson JL, et al. J Am Coll Cardiol . 2007;50:e1-e157, Figure 7. ACT = anticoagulation therapy; LOE = level of evidence. A B B1 B2 Prior to Angiography Init at least one (Class I, LOE: A) or both (Class IIa, LOE: B) of the following: Clopidogrel IV GP IIb/IIIa inhibitor Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include: Delay to Angiography High Risk Features Early recurrent ischemic discomfort
  • 38. Initial Invasive Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial invasive strategy is selected, antiplatelet therapy in addition to ASA should be initiated before diagnostic angiography (upstream) with either clopidogrel (loading dose followed by daily maintenance dose)* or an IV GP IIb/IIIa inhibitor . (Box B2) Abciximab (ReoPro) as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide (Integrilin) or tirofiban (Aggrastat) is the preferred choice of GP IIb/IIIa inhibitor.† *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established; †Factors favoring administration of both clopidogrel and a GP IIb/IIIa inhibitor include: delay to angiography, high-risk features, and early ischemic discomfort. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
  • 39. Initial Invasive Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to initiate antiplatelet therapy with both clopidogrel (loading dose followed by daily maintenance dose)* and an intravenous GP IIb/IIIa inhibitor . (Box B2) Abciximab as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide or tirofiban is the preferred choice of GP IIb/IIIa inhibitor.† *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established; †Factors favoring administration of both clopidogrel and a GP IIb/IIIa inhibitor include: delay to angiography, high-risk features, and early ischemic discomfort. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
  • 40. Initial Invasive Strategy: Anticoagulant Therapy Anticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients as soon as possible after presentation. For patients in whom an invasive strategy is selected, regimens with established efficacy at a Level of Evidence: A include enoxaparin (Clexane ® ) and unfractionated heparin (UFH) (Box B1), and those with established efficacy at a Level of Evidence: B include bivalirudin (Angiomax ® ) and fondaparinux (Arixtra ® ) (Box B1). I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A New Drugs
  • 41. Initial Conservative Strategy Major Changes New Drugs Longer Duration of Rx Revised Algorithm
  • 42. Init clopidogrel (Class I, LOE: A) Consider adding IV eptifibatide or tirofiban (Class IIb, LOE: B) Conservative Strategy Init ACT (Class I, LOE: A): Acceptable options: enoxaparin or UFH (Class I, LOE: A) or fondaparinux (Class I, LOE: B), but enoxaparin or fondaparinux are preferable (Class IIa, LOE: B) Select Management Strategy ASA (Class I, LOE: A) Clopidogrel if ASA intolerant (Class I, LOE: A) Diagnosis of UA/NSTEMI is Likely or Definite Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy Proceed with Invasive Strategy (Continued) Anderson JL, et al. J Am Coll Cardiol . 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy; LOE = level of evidence. C2 C1 A
  • 43. Any subsequent events necessitating angiography? EF greater than 40% Evaluate LVEF Low Risk Cont ASA (Class I, LOE A) Cont clopidogrel (Class I, LOE A) and ideally up to 1 yr (Class I, LOE B) DC IV GP IIb/IIIa if started previously (Class I, LOE A) DC ACT (Class I, LOE A) (Class I, LOE: B) Proceed to Dx Angiography Yes EF 40% or less Stress Test (Class I, LOE: A) No Not Low Risk (Class IIa, LOE: B) Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy (Continued) Anderson JL, et al. J Am Coll Cardiol . 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy; LOE = level of evidence. (Class I, LOE: A) (Class IIa, LOE: B) O L M N K E-1 E-2 D (Class I, LOE: B) (Class I, LOE: A)
  • 44. Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, clopidogrel (loading dose followed by daily maintenance dose)* should be added to ASA and anticoagulant therapy as soon as possible after admission and administered for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B) (Box C2) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
  • 45. Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, HF, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed . (Level of Evidence: A) (Box D) Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban; Level of Evidence: A ) or clopidogrel (loading dose followed by daily maintenance dose; Level of Evidence: A) * should be added to ASA and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C) *Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established. See recommendation for LOE I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
  • 46. Initial Conservative Strategy: Antiplatelet Therapy For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy. (Box C2) Abciximab should not be administered to patients in whom PCI is not planned. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
  • 47. Initial Conservative Strategy: Anticoagulant Therapy Anticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients as soon as possible after presentation. For patients in whom a conservative strategy is selected, regimens using either enoxaparin* or UFH (Level of Evidence: A) or fondaparinux (Level of Evidence: B) have established efficacy. (Box C1) In patients in whom a conservative strategy is selected and who have an increased risk of bleeding, fondaparinux is preferable. (Box C1) B *Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A New Drugs
  • 48. Initial Conservative Strategy: Anticoagulant Therapy For UA/NSTEMI patients in whom an initial conservative strategy is selected, enoxaparin* or fondaparinux is preferable to UFH as anticoagulant therapy, unless CABG is planned within 24 h. *Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
  • 49. Initial Conservative Strategy: Additional Management Considerations For UA/NSTEMI patients in whom an initial conservative strategy is selected and no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), a stress test should be performed. (Box O) a. If, after stress testing, the patient is classified as not at low risk, diagnostic angiography should be performed. (Box E1) This recommendation continues on the next slide. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
  • 50. Initial Conservative Strategy: Additional Management Considerations b. If, after stress testing, the patient is classified as being at low risk (Box E2) , the instructions noted below should be followed in preparation for discharge (Box K) : Continue ASA indefinitely. (Level of Evidence: A) Continue clopidogrel for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B) Discontinue IV GP IIb/IIIa inhibitor if started previously. (Level of Evidence: A) Continue UFH for 48 h or administer enoxaparin or fondaparinux for the duration of hospitalization, up to 8 d, and then discontinue anticoagulant therapy. (Level of Evidence: A) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III A
  • 51. Initial Conservative Strategy: Additional Management Considerations For UA/NSTEMI patients in whom an initial conservative strategy is selected and in whom no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), LVEF should be measured. (Box L) If LVEF is ≤ 40%, it is reasonable to perform diagnostic angiography. (Box M) If LVEF is > 40%, it is reasonable to perform a stress test. (Box N) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
  • 52. Cardiac cath CAD No Discharge from protocol Yes Left main disease Yes CABG No 1- or 2- Vessel Disease 3- or 2-vessel disease with proximal LAD involvement LV dysfunction or treated diabetes* No PCI or CABG Medial Therapy, PCI or CABG Yes CABG *There is conflicting information about these patients. Most consider CABG to be preferable to PCI. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 20. Revascularization Strategy in UA/NSTEMI
  • 53. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) At the time of preparation for hospital discharge, the patient’s need for treatment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach to treatment should be used for selection of treatments. Pain relief should begin with acetaminophen, small doses of narcotics, or nonacetylated salicylates. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
  • 54. NSAIDs It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, small doses of narcotics, or nonacetylated salicylates is insufficient. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III C New
  • 55. Stepped-Care Approach to Pharmacological Therapy for Musculoskeletal Symptoms With Known Cardiovascular Disease or Risk Factors for Ischemic Heart Disease *Addition of ASA may not be sufficient protection against thrombotic events. Reproduced with permission from Antman EM, et al. Circulation 2007;115:1634–42. PPI = proton-pump inhibitor. Acetaminophen, ASA, tramadol, narcotic analgesics (short term) Nonacetylated salicylates Non COX-2 selective NSAIDs NSAIDs with some COX-2 selectivity COX-2 selective NSAIDs Select pts at low risk of thrombotic events Prescribe lowest dose required to control symptoms Add ASA 81 mg and PPI to pts at ↑ risk of thrombotic events* Regular monitoring for sustained hypertension (or worsening of prior BP control), edema, worsening renal function, or GI bleeding If these occur, consider reduction of the dose or discontinuation of the offending drug, a different drug, or alternative therapeutic modalities, as dictated by clinical circumstances New
  • 56. ED Management Strategies: Guidelines at a Glance (See full text for indications and contraindications of listed elements; &quot;check&quot; mark = generally indicated; +/– = possibly indicated; – = generally not indicated.)