Acute Coronary Syndrome Alena Goldman, MD September 16, 2004

Things to Know…. What is ACS? Quick recognition of ACS? Classification (think simple… ACS/NSTEMI vs. STEMI) Sick or not sick (i.e. cath lab/thrombolytics fast?) Management

What is ACS? ACS = Unstable angina / NSTEMI/ STEMI

Pathophysiology Stable USA NSTEMI STEMI Angina Fixed Plaque Plaque Occluding Plaque Rupture Rupture Thrombus + + Evidence of Myocardial Myocardial Damage Damage

Recognition of ACS History:   Rest angina, which is usually more than 20 minutes in duration   New onset angina that markedly limits physical activity   Increasing angina that is more frequent, longer in duration, or occurs with less exertion than previous angina

Recognition of ACS ECG: USA/NSTEMI are also called the non-STelevation acute coronary syndromes, i.e. ST elevation and pathologic Q waves are absent Can see: ST depressions or transient elevations or new T wave inversions STEMI: ST elevations/reciprocal changes

Recognition of ACS Markers of Myocardial Injury: USA: with ischemic symptoms suggestive of an ACS and no elevation in troponins or CK-MB, with or without ECG changes NSTEMI: same manifestations as those in USA, but in whom an elevation in troponins or CK-MB is present STEMI: ischemic symptoms; ST elevations or pathologic Q waves; elevated troponins or CK-MB

Importance of Early Recognition!!! Early interventions, regardless of strategy used, save lives!!! In addition to reduction in mortality: Reduce infarct size (reperfusion) Preserve LV function/prevention of LV remodeling (ACE-I) Prevent recurrent ischemia and arrhythmias (beta blockers) Slow disease progression (statins) Cholesterol lowering (statins)

Recognition Triage (sick vs. not sick) Hemodynamically unstable: signs of cardiogenic shock (with massive STEMI: large anterior wall MI or inferior MI with RV involvement) Malignant ventricular arrhythmias Triage to: cath lab/balloon pump/pressors/CCU

Recognition Triage (sick vs. not sick) 2. STEMI: anginal sxs plus ST elevations 1 mm of greater in two contiguous leads or new LBBB Triage cath lab vs. lytics if primary PCI not available

Recognition Triage (sick vs. not sick) 3. Refractory chest pain: If good story, elevated markers, suggestive ECG changes: Triage cath lab

Management Sick  cath vs lytics if STEMI STEMI  cath vs. lytics USA/NSTEMI medical management plus reperfusion (PCI)

USA/NSTEMI: Goals of Therapy Relief of ischemic pain Assessment of hemodynamic state and correction of abnormalities Antithrombotic therapy: -prevent further thrombosis and progression to STEMI -prevent embolization of plaque

USA/NSTEMI: Therapy Should NOT receive thrombolytics (as opposed to STEMI) Lack of benefit due to the fact that the infarct-related artery is at least partially patent at early angiography in 60 to 85 percent of cases

USA/NSTEMI: Therapy Early PCI vs. Medical Management? data from TACTICS-TIMI 18: Primary PCI better especially if + troponin, ST changes, recurrent angina, TIMI score >3, sustained VT, HD instability, h/o prior PCI or CABG

USA/NSTEMI: TIMI score TIMI 11B and ESSENCE trials: Age 65 years    Presence of at least three risk factors for CHD    Prior coronary stenosis of 50 percent    Presence of ST segment deviation on admission ECG    At least two anginal episodes in prior 24 hours    Elevated serum cardiac biomarkers    Use of aspirin in prior seven days

USA/NSTEMI: Initial Therapy Aspirin Heparin gtt Beta blocker Nitro gtt (careful if suspect inferior/RV involvement and if h/o AS) ….In addition to MONA (Morphine, Oxygen, SL NTG, ASA 81 mg); IV; cardiac monitor

ACS/NSTEMI: ASA -Antiplatelet function -Administration reduces incidence of death and subsequent MI -Dose: 160 mg to 325 mg immediately followed by 75 mg to 325 mg indefinitely -Contraindications: allergy; hemophilia; active bleeding; active retinal hemorrhage; active PUD -If allergic to ASA Plavix

USA/NSTENI: Plavix or Ticlid As effective as ASA Plavix preferred over Ticlid as it inhibits platelets more rapidly and has less side effects CURE trial: combo of Plavix plus ASA compared to ASA alone showed decreased cardiovascular death, MI and stroke In patients undergoing PCI: administration of Plavix 6 hours prior to PCI improves outcome (fewer acute thrombotic complications) Problem: if patient needs CABG, increased bleeding and reoperation risk

USA/NSTEMI: IIb/IIIa inhibitors Benefits in high risk patients (TIMI score ≥4) or if planned PCI Tirofiban, eptifibatide, abciximab Infused for 48 to 72 hours, or until PCI Small but significant increase in major bleeding (no increase in ICH)

USA/NSTEMI: Anticoagulation Heparin: -interferes with thrombus formation by different mechanism than ASA -associated with rebound chest pain if discontinued -unclear if has efficacy after 24 to 48 hours -studies show trends towards mortality benefit (Meta Analysis, JAMA 1996)

USA/NSTEMI: Anticoagulation LMWH -meta-analysis of ESSENCE and TIMI 11B: enoxaparin vs. unfractionated heparin, an improvement in outcome with enoxaparin, with a 20 percent reduction in death and ischemic events -Benefits of LMWH: easy administration; no need to follow PTT; mortality benefit; can be used before planned PCI -Problems with LMWH: should not be used in renal failure (Creatinine clearance less than 30); should not use if planned CABG in 24 hours

USA/NSTEMI: Anticoagulation Direct Thrombin Inhibitors hirudin, lepirudin, bivalirudin Decreased incidence of MI compared to heparin but no mortality benefit Very expensive Can be used if h/o HIT

USA/NSTEMI: beta blockers Decrease death by 20-30% Do not use in symptomatic bradycardia; high degree AV block; decompensated CHF; hypotension

USA/NSTEMI: Further Medical Management ACE Inhibitors -More studies done in patients after STEMI, but likely benefit in all patients after myocardial infarction -Class I recommendations in patients with left ventricular dysfunction or heart failure, diabetes, and/or hypertension despite therapy with a beta blocker -Begin therapy in first 24 hours in the absence of contraindication -HOPE trial (patient without MI): benefit of chronic therapy with ACE-I

USA/NSTEMI: Further Medical Management ARBs -limited data -probably should not use combination of ACE-I and ARB (VALIANT trial)

USA/NSTEMI: Further Medical Management Statin Therapy PROVE IT-TIMI 22 trial suggests that benefit from statin therapy is seen with serum LDL-cholesterol values below 100 mg/dL and that the goal LDL-cholesterol concentration should be less than 80 mg/dL should be initiated prior to discharge from the hospital in patients with an ACS (between 24 and 96 hours after hospital admission) trend toward benefit as early as 30 days

USA/NSTEMI: Further Medical Management Aldosterone Antagonists -EPHESUS trial: Eplerenone was given to patients post MI; LVEF<40; renal failure or diabetes -significantly lower rate of all-cause mortality -serum potassium should be monitored closely

USA/NSTEMI: Should NOT GET… Prophylactic antiarrhythmics Digoxin CCB

STEMI: Quick Recognition!!! Story ECG Serum cardiac enzyme elevation

STEMI: Reperfusion Therapy thrombolytic agents or primary (direct) PCI: Decision has to be made FAST since prompt restoration of myocardial blood flow is essential to myocardial salvage

STEMI: Primary PCI High quality PCI should be immediately available Enhanced survival with lower are of ICH and recurrent MI Rapid transfer to a PCI center can still produce better outcomes than thrombolysis, as long as the door-to-balloon time is less than two hours

STEMI: Primary PCI, Cont’d Restores normal epicardial flow in more than 90 percent of cases compared to only 50 to 60 percent with thrombolysis Mechanical revascularization (usually by PCI) is also the preferred therapy in patients who have contraindications to thrombolysis In the United States, the median time to PCI after arrival at the hospital is 116 minutes, and exceeds two hours in 46 percent The longer the door-to-balloon time, the greater the infarct size TIMI 3 flow is achieved in over 90 percent of patients treated with primary PCI

STEMI: Thrombolysis If PCI not available in 2 hours, patient should be rapidly evaluated for thrombolytic therapy R/O Contraindications: evidence of active bleeding, history of cerebrovascular disease, intracranial neoplasm, systolic blood pressure greater than 175 mmHg, trauma, or drug allergy If no contraindications exist, intravenous thrombolysis should be given within 30 minutes from emergency department presentation

STEMI: Thrombolysis Should be administered within the first four hours and particularly within the first 70 minutes of symptom onset Most patients present >2 hours after onset of symptoms Utility of prehospital lytics if transport time >60 min

STEMI: Choosing Lytics (from S. Parpos, MD)

STEMI: Lytics Morbidity and mortality benefit is primarily seen in the 50 to 60 percent of patients who develop TIMI grade 3 flow Possible alternative: combination therapy using a half-dose of a thrombolytic agent combined with a GP IIb/IIIa inhibitor: -more likely to restore coronary perfusion -two large trials failed to show a survival benefit compared to conventional thrombolytic therapy

STEMI: Delayed Reperfusion Optimal reperfusion strategy is less clear when the door-to-balloon time will be more than two to three hours Thrombolytic therapy administered more than 12 hours after the onset of acute myocardial infarction does not improve clinical outcome Early PCI is also optimal but, in contrast to thrombolysis, revascularization after 12 hours with PCI may be of some benefit

STEMI: Antiplatelet Agents ASA Plavix or Ticlid: extrapolated data from NSTEMI; most get plavix load in cath lab prior to stent placement -Limited data on addition of plavix to asa in patients treated with lytis -Continue plavix for 9-12 months IIB/IIIA inhibitors: -used in primary PCI -so far not recommended in patients receiving lytics

STEMI: Medical Therapy Nitro ggt Beta Blockers K and Mg repletion: HypoK in AMI: risk for VF Glucose control

STEMI: Anticoagulation Heparin or LMWH With PCI With Lytics (if getting asa and alteplase) Without reperfusion 24-48 hours Coumadin -Evidence for use one to three months post-MI in patients at high risk for embolization, especially those with an anterior wall MI (LV thrombus/aneurism; LVEF<30%; h/o thromboembolic disease; h/o afib)

STEMI: Further Medical Management Repeat reperfusion therapy ACE Inhibitors ARB Statin therapy Aldosterone Antagonists Risk stratification

ACS: Take Home Points Quick recognition HD stable? USA/NSTEMI vs STEMI STEMI reperfusion (door to balloon time <90 min; door to lytics <30 min) USA/NSTEMI: no benefit in lytics All get: MONA; ASA; nitro; beta blockers; heparin or LMWH High risk patients get IIb/IIIa inhibitors

ACS: Take Home Points USA/NSTEMI patient should get Plavix unless expect CABG Primary PCI is superior to conservative management in USA/NSTEMI patients Adjunctive therapy: ACE-I, ARB, statins Coumadin in patients with LV aneurism/thrombus, LV dysfunction Post MI patients need risk stratification for primary prevention of sudden cardiac death