An update on the management of UA / NSTEMI Michael H. Crawford, MD
New ACC/AHA Guidelines 2007 What s s new in the last 5 years CT imaging advances Ascendancy of troponin and BNP Clarification of ACEI/ARB use Increased use of clopridigrel,, platelet GPIIa/IIIb, LMWHeparin, fondaparinox and bivalrudin Aggressive lipid management Invasive management of higher risk patients
CT Angiography 2007 Guidelines Class lla Suspected ACS with low to intermediate probability of CAD, non-diagnostic ECG, normal biomarkers: CT angiography is an alternative to stress testing.
Advantages of CTA Highly sensitive, high negative predictive value. Logistically easier than stress testing.
Disadvantages of CTA Specificity and positive predictive value modest Relatively high radiation exposure Often need beta blocker acutely. Requires contrast
ESC/ACC Definition of Acute MI Typical increase and gradual decrease of Troponin or more rapid increase and decrease of CK-MB with at least one of: 1. ischemic symptoms 2. new ST-T T wave changes of ischemia or new LBBB 3. development of Q waves on ECG 4. Imaging evidence of new regional wall motion abnormality
ESC/ACC Definition of Acute MI Sudden cardiac death plus new ST elevation, LBBB, positive angio or path 3xULN cardiac biomarkers post PCI 5xULN cardiac biomarkers post CABG plus Q waves, LBBB, graft/vessel closure or positive imaging Pathological findings of acute MI
Brain Natriuretic Peptide or NT-pro pro-bnp Better predictor of mortality then troponin Highly sensitive for LV dysfunction Highly sensitive for heart failure Class IIb for triage of ACS
ROC curve concerning death at 30 days for NT-proBNP and ctnt in study population (A) and for NT-proBNP in patients with STEMI and NSTE-ACS (B) Galvani, M. et al. Circulation 2004;110:128-134 Copyright 2004 American Heart Association
Association between NT-proBNP and death at 30 days according to clinical diagnosis in study population (A) and in Killip class 1 patients without a history of previous heart failure (B) Galvani, M. et al. Circulation 2004;110:128-134 Copyright 2004 American Heart Association
ACEI / ARBs Class I indications Heart failure EF <40% Hypertension Diabetes Class IIa All ACS patients (HOPE)
ACEI for Stable CAD Patients Baseline HOPE EUROPA PEACE Number: 9,297 12,218 8,290 Finished: 1995 2000 2000 Follow-up: 5 yrs 4 yrs 5 yrs CAD: 80% 100% 100% EF < 40%: 8% < 1% < 0.1% Anti plt: 76 92 91 BB: 40 62 60 Lipid: 29 57 70
ACEI for Stable CAD Patients OR, P HOPE EUROPA PEACE Mortality:.83,.005.89,.09.88,.13 MI:.77,.002.77,.001 1.0,.98 Stroke:.68,.0003.96,.77.76,.09 CHF:.88,.27.61,.002.77,.05 PCI:.88,.14.96,.60 1.03,.62
Anticoagulation Management of Invasive Strategy Class I Clopridogrel or IIb/IIIa antagonists abciximab if immediate intervention eptifibatide or tirofiban if delayed intervention Class IIa administer both
Platelet GP IIb/IIIa Inhibitors 6 Trials 14,704 NSTE-ACS with PCI EPIC, EPILOG, CAPTURE, RESTORE, IMPACT, EPISTENT Primary end-point = death, MI, urgent revascularization PEP RRR 33-59% p.02 - <.001 Abciximab benefit in CAPTURE and ISAR-REACT REACT only if troponin elevated
Platelet GP IIb/IIIa Inhibitors 4 Trials 18,377 High Risk NSTE- ACS Conservative Rx PARAGON, PRISM, PRISM-PLUS, PLUS, PURSUIT GP IIb/IIIa s lamifiban, tirofiban, eptifibatide Primary end-point = death, MI, recurrent ischemia 30d PEP modestly reduced p =.04 to <.03
PARAGON B 5,225 NSTE-ACS No PCI lamifiban vs. placebo Primary end-point = death, MI, recurrent ischemia PEP not different 30d Pos. troponin, IIb/IIIa 11% vs. 19% p =.01 GUSTO IV ACS trial abciximab with conservative management was not beneficial
GP IIb/IIIa Agents Most effective in patients undergoing PCI, especially abciximab High risk patient, catheterization delayed, use small molecule agents GP IIb/IIIa + clopidogrel not well studied,? increased bleeding
Heparins / Fondaparinox / Bivalrudin UFH preferred if immediate catheterization or CABG in 24 hours. LMWH preferred in cath delayed or conservative strategy Bivalrudin if heparins contraindicated Fondaparinox preferred if history of bleeding
Unfractionated Heparin vs. Low Molecular Weight Heparin Advantages of LMWH: Ease of use no ACT monitoring Reduced event rate vs. heparin in some studies (ESSENSE, TIMI 11)
Unfractionated Heparin vs. Low Molecular Weight Heparin Disadvantages of LMWH: Difficult to assess degree of anticoagulation for procedures Less effective reversal with protamine Caution in those with renal impairment Increased bleeding in some studies (SYNERGY)
Copyright 2007 American College of Cardiology Foundation. Restrictions may apply. ACUITY Clinical Outcomes at 30 D Anderson, J. L. et al. J Am Coll Cardiol 2007;50:652-726
Copyright 2007 American College of Cardiology Foundation. Restrictions may apply. ACUITY Composite Ischemia and Bleeding Outcomes Anderson, J. L. et al. J Am Coll Cardiol 2007;50:652-726
Fondaparinux in ACS? Compared to enoxaparin - equal or better at reducing MACE Significantly less major bleeding Once a day dosing because of long T1/2 Lower cost Increase in guide wire thrombus at cath OASIS-5 5 investigators. N Engl J Med 2006;354:1464-76
Copyright 2007 American College of Cardiology Foundation. Restrictions may apply. OASIS Cumulative Risks of Death, MI, or Refractory Ischemia Anderson, J. L. et al. J Am Coll Cardiol 2007;50:652-726
Lipid Management Class I Statins for all LDLC < 100 mg/dl Non HDLC < 130 mg/dl
Lipid Management Class IIa LDLC < 70 mg/dl Non HDLC < 100 mg/dl Triglycerides < 200 mg/dl HDLC > 40 mg/dl
Lipid Management Class IIb fish oil (1g/day) Class III Antioxidant vitamins Folic acid
MIRACL: Study Design Hospitalization for unstable angina or non Q-wave MI N=3,086 randomized 24 96 h after admission Placebo + diet Atorvastatin 80 mg + diet 16 wk Assessments conducted at wk 2, 6, and 16 Schwartz GG et al. JAMA. 2001;285:1711-1718.
15 MIRACL: Time to First Ischemic Event* Placebo 17.4 14.8 10 Cumulative incidence (%) 5 Atorvastatin RR = 0.84 (95% CI, 0.70-1.00) P = 0.048 0 0 4 8 12 16 Time since randomization (wk) *Death (any cause), nonfatal MI, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization. Schwartz GG et al. JAMA. 2001;285:1711-1718.
MIRACL: Fatal or Nonfatal Stroke 2.0 1.5 RR = 0.50 (95% CI, 0.26-0.99) P = 0.045 Placebo 1.6 Cumulative 1.0 incidence (%) Atorvastatin 0.8 0.5 0.0 0 4 8 12 16 Time since randomization (wk) Data from Schwartz GG et al. JAMA. 2001;285:1711-1718.
Copyright 2007 American College of Cardiology Foundation. Restrictions may apply. Relative Risk of Outcomes With Early Invasive Versus Conservative Therapy in UA/NSTEMI Anderson, J. L. et al. J Am Coll Cardiol 2007;50:652-726
Invasive Strategy Preferred Recurrent pain despite medical therapy Elevated troponin New ECG ST depression Heart failure, worsening MR High risk stress test or CTA Hemodynamic instability Ventricular tachyarrhythmias PCI <6 months, prior CABG EF < 40%