Treatment of Acute Coronary Syndromes

Transcription

1 Treatment of Acute Coronary Syndromes UC SF Jeffrey Tabas, M.D. sf g h Associate Professor UCSF School of Medicine Emergency Services, San Francisco General Hospital Objectives Review the updated AHA/ACC guidelines for TREATMENT of patients with STEMI (2008) and UA/NSTEMI (2007) Discuss them with a critical eye and review the challenges and pitfalls in application of these guidelines ACC/AHA Guidelines ACC/AHA Guidelines AMI 2000, 2002, Non ST Elevation MI/USA 2004, ST Elevation MI AMI 2000, 2002, Non ST Elevation MI/USA 2004, ST Elevation MI Website = ACC.Org Website = ACC.Org

2 ACC/AHA Guidelines AMI 2000, 2002, Non ST Elevation MI/USA 2004, ST Elevation MI Effect of Treatment From 1980 to 2000 Age-adjusted rate of coronary artery death fell significantly 5.4 to 2.7 per 1000 in men 2.6 to 1.3 per 1000 in women Website = ACC.Org What is responsible for improvement? Chronic Care Lower cholesterol Earlier identification of CAD Acute Care Aspirin Rapid Defibrillation 2 Monitoring Rapid Reperfusion Cost of ACS Excess spending on health care administration in the United States compared with Canada $100 billion/year* Estimated cost for admission and inpatient evaluation of patients with chest pain $3-10 billion/year Estimated value of this lecture? *Woolhandler, NEJM, 03

3 Understanding NNT vs NNH NNT (to prevent one death) = 10 End of the Day What do they mean? How do we calculate them? How do we use them? UNTREATED TREATED W/ DRUG End of the Day Number Needed to TREAT Number Needed to TREAT Thrombolytics decreases mortality by 25% If baseline mortality = 4% => Absolute benefit = 1% If baseline mortality = 20% => Absolute benefit = 5% NNT = 100 benefit (%) 1% mortality benefit => NNT = 100 5% mortality benefit => NNT = 20

4 Number Needed to TREAT Number Needed to HARM NNT depends on: 1. Effectiveness of Rx (relative benefit) 2. Severity of disease (baseline mortality/morbidity) 3. Accuracy of patient selection NNT = 100 => BUT if only half your patients have disease NNT = 200! NNH 1% of patients bleed into their head with Rx NNH = 100 NNH NOT affected by disease severity NOT affected by accuracy of selection NNT vs NNH NNT vs NNH Use a therapy when NNT outweighs NNH (assuming accurate Summary selection of patients in plain with disease) language: NNT = 10 NNH = 100 Patients with PROVEN disease (100% rule in rate) may benefit from therapy while patients with SUSPECTED (< 100% rule in) disease may be harmed by that same = 10% therapy! What is the minimum rule in rate to make this Rx beneficial? Use a therapy when NNT outweighs NNH (assuming accurate selection of patients with disease) NNT = 10 NNH = 100 What is the minimum rule in rate to make this Rx beneficial? = 10%

5 ACS Diagnosis ACS Diagnosis Definite ACS (85%) 1) Ischemic ECG or 2) Diagnostic cardiac marker elevation Possible ACS (15%) 1) Good story 2) Possibly ischemic ECG 3) Trace cardiac marker elevation Troponin I = 4.5 Troponin I = 0.06 ACS Diagnosis Treatments for ACS Probably not ACS (<5%) 1) Atypical Story 2) Non-ischemic ECG 3) Normal cardiac markers Troponin I < 0.04 Things that don t make you bleed Aspirin Oxygen Nitrates Beta Blockers Morphine ACE inhibitors Statins

6 Treatments for ACS Things that make you bleed Heparin GP2B3A inhibitors Clopidogrel Thrombolytics Aspirin Clear benefit with minimal downside! GIVE IT TO EVERYONE NOT ALLERGIC! Equivalent benefit to thrombolytics NNT to prevent death/mi/cva = STEMI and NSTE-ACS : Class 1 ISIS-2, Lancet, 1988 NSAIDs Discontinue NSAIDs in patients with acute coronary syndrome Oxygen Unclear benefit unless hypoxic Minimal downside Especially if they are being used to treat the cardiac chest pain! STEMI and NSTE-ACS: Class 2a Class 1 if hypoxic

7 Nitroglycerin No clear benefit NNT = 260 to prevent death NNH = 120 to cause profound hypotn STEMI and NSTE-ACS - Class 1 GISSI-3 and ISIS-4 Indications for IV Nitrates Benefit largely from prethrombolytic era data Persistent Ischemia Large Anterior MI MI and CHF MI and Hypertension Contraindications to Nitrates Beta-Blockers Blockers and MI Bradycardia (<50) Tachycardia Hypotension (caution in RVMI) Sildenafil or Vardenafil < 24 hours, or Tadalafil < 48 hours Commit Trial 46,000 Chinese STEMI pts NNT to prevent Death/MI/Arrest = 100 NNH (Cardiogenic Shock) = 100 HOWEVER - Included Class 3 Heart Failure Patients Chen, Lancet, 2005

8 Beta-Blockers Blockers and MI GUIDELINE REVISION STEMI and NSTE-ACS: Class 1: Oral beta-blockers should be given in the first 24 hours. Class 2a: Immediate intravenous b-blocker if hypertensive AVOID IF PATIENT IS AT RISK FOR COMPLICATIONS Contraindications to Acute B-Blocker B Blocker treatment CHF/ LV dysfunction (HR < 60, SBP < 100, age > 70, SBP < 120) Conduction blocks COPD/ Asthma/ DM/ PVDz/ Cocaine y.o. F complains of feeling weak. Smokes, high cholesterol 73 y.o. F complains of feeling weak. Smokes, high cholesterol

9 Morphine Reasonable to use in the truly ischemic patient Associated with worse outcomes in observational studies. NSTE-ACS Downgraded to Class IIa. STEMI Class I ACE Inhibitors Should be given in the first 24 hours in absence of contraindications (especially with CHF but SBP >100). May be associated with cardiogenic shock A lot like beta blockers! NNT = 200 STEMI / NSTE-ACS: Class 1 oral in the 1st 24 hrs ISIS-4, 1995 GISSI-3, 1994 Statins For secondary prophylaxis (documented CAD) For primary prophylaxis if extremely high risk

10 Use Protection *Gastroprotection* - Use PPI or H2 Blockers if history of GI bleeding Treatments that cause bleeding Heparin GP2B3A inhibitors Clopidogrel Thrombolytics Is Heparin better than Placebo? No Δ death/revasc/recurrent angina Magee et al, Cochrane Database, pts with NSTE-ACS rx d with ASA NNT (prevent MI) = 33 NNH (major bleed) = 150? The benefit disappears after heparin stopped Benefit if not definitely ACS? TIMI 11b, Circ, 1999 Compared IV UFH vs LMWH 3900 pts with UA/NSTEMI BUT after 1800 pts, study was stopped and changed to include only pts with ST changes or positive cardiac markers!

11 Is LMWH better than UFH? Murphy, Eur HJ,07 - Meta-analysis of 47,000 pts NSTE-ACS - minimal 1.1% less reinfarct No change in major bleeds STEMI - minimal 1.7% less re-infarct 0.8% more major bleeds Heparin with Thrombolytics in STEMI Eikleboom, Circ, 2005 (40,000 pts) UFH No benefit or harm LMWH NNT (prevent MI/death) = 50 NNH (major bleed) = 140 IV UFH Heparin Dosing Load with 60u/kg Max = 4000 Infusion at u/kg Max = mg/kg BID Enoxaparin Dosing Dose with TNK: 30mg IV + 1mg/kg SQ Adjust dose for Age > 75 (No bolus and decrease drip to 0.75 mg/kg) Adjust dose for Creatinine > (No bolus)

12 Heparin Bottom Line NSTE-ACS/ STEMI w/o reperfusion Class 1 LMWH, UFH, Fondaparinux, (or Bivalirudin for cath) STEMI + Thrombolytics Class 1 LMWH, UFH, Fondaparinux STEMI + PCI Whatever the cardiologist wants Glycoprotein 2b3a inhibitors What are they? Abciximab (REOPRO) PCI Only Eptifibatide (Integrelin) ACS or PCI Tirofiban (Aggrastat) ACS or PCI Glycoprotein 2b3a inhibitors How do they work? All are given IV Platelets adhere via vwf stimulating the GP 1b receptor Platelets aggregate via Fibrinogen stimulating the GP2b3a receptor Glycoprotein 2b3a inhibitors How much do they cost? $ for usual course of therapy

13 GP2b3a - Recommendations in ACS When PCI is planned In medically managed patients with: Continuing ischemia Elevated troponin Other high risk features Do They Improve Outcomes? Clear Benefit In Patients Receiving PCI All Three 2b3a s No Evidence Clearly Supports benefit in medically managed patients! Schriger, Ann EM, 01 Boersma, Lancet, 02 Should we start 2b3a s s in ED? NO BENEFIT!!!!!!!!!!! But it is recommended to start upstream either clopidogrel or 2b3a s Keeley, Lancet, 06 Clopidogrel ADP receptor antagonist Give it to all Aspirin allergic pts Give in addition to ASA for UA/NSTEMI patients not going to cath Class 2a in STEMI for pts < 75 y.o receiving thrombolytics Contraindicated if risk of CABG

14 Clopidogrel CURE (Yusuf, NEJM, 2001) 12,500 pts w/ UA/NSTEMI CVA/ MI/ Death: 11.5% vs 9.3% Major bleed: 2.7% =>3.7% Stopped after 3000 patients and changed to include only pts w/ ST depression or elevated troponin! Clopidogrel Summary Some feel strongly to give in ED - I find no evidence of benefit. STEMI Class 1 to give 75 mg, but doesn t say when Class 2a to give 300 mg, if <75 y.o and not going to cath NSTE-ACS Class 1 if allergic to ASA Class 1 if going to Cath to give upstream Clopidogrel or 2b3a Thrombolytics - Indications Thrombolytics 1mm STE in 2 contiguous leads, or presumed new LBBB Sx s < 12 hours NNT = to prevent 1 death Each hour delay leads to 1.6 more deaths per 1000 pts Complications: ICH in % Transfusion in 5-15%

15 Reduced dose lytics + 2b3a No Mortality Benefit Hemorrhage increased by 2% DRIP & SHIP? Gusto-V, Lancet 2001 ASSENT-3, Lancet 01 YES if you want to kill them and spend a lot of money doing so Keeley, Lancet, 06 Contraindications for lytics in AMI PCI vs Lytics in ST elevation TNK Guidelines CVA at any time Known bleeding diathesis (INR>2 on coumadin) Severe uncontrolled hypertension (BP > 180/110) Intracranial neoplasm, aneurysm, AVM Intracranial or intraspinal surgery < 2 mos. Active internal bleeding ase-prescribing.pdf Accessed PCI shows 6% greater reduction (absolute) in Death/MI/CVA than lytics NNT = 16 Keeley, Lancet, 2003 Meta-analysis of 23 trials Thrombolytics = 14% adverse outcome rate PCI = 8% adverse outcome rate

16 Advances in PCI Probable Benefit in UA/NSTEMI Tactics-Timi 18, Frisc-2 No need for in house surgical backup Aversano, JAMA, 2002 Advances in PCI Transfer to PCI is worth the delay Anderson, NEJM, 2003 Transfer for PCI (< 2 hrs) vs Thrombolytics Adverse outcomes decreased from 14.2% to 8.5% (death, reinfarct, stroke) Recommendations Door to ballon time < 90 minutes At least 75/yr by MD At least 200/yr by institution (400 preferred) Summary of ED Therapy for ACS Summary of ED Therapy for ACS Oxygen no clear benefit unless hypoxic ASA Beta blockers Careful selection Therapies that inhibit coagulation and platelets are primarily of benefit in the presence of an ischemic ECG or elevated cardiac markers Nitrates no clear benefit Pain Control = narcotics no clear benefit

17 Summary of ED Therapy Summary of ED Therapy STEMI with PCI available: Select meds in discussion with your cardiologist Heparin If used, can be started in ED - Unfractionated vs LMWH Clopidogrel Often given at cath instead of ED GP 2b3a s If used, controversy to start in ED - Not for medical management! Bivalirudin Used without heparin or GP2b3a s STEMI with only Lytics available: Thrombolytic and Heparin Per protocol Clopidogrel Maybe GP 2b3a s Probably not Summary of ED Therapy for UA/NSTEMI Heparin IV UFH vs LMWH Clopidogrel No clear benefit GP 2b3a s No clear benefit Early invasive strategy Evidence is mounting, but not yet definitive