Acute Coronary Syndromes: Different Continents, Different Guidelines?

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2 Acute Coronary Syndromes: Different Continents, Different Guidelines? Robert A. Harrington MD, MACC, FAHA, FESC Arthur L. Bloomfield Professor of Medicine Chair, Department of Medicine Stanford University

3 Disclosure Statement of Financial Interest Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed below. Research grants/contracts: NHLBI, PCORI, Duke, Harvard, Astra, CSL, GSK, Janssen, Merck, Novartis, Portola, sanofi-aventis, TMC Consulting/Advisory: Adverse Events, Amgen, Element Science, Gilead, Merck, MyoKardia, TMC, Vida Health, WebMD Board of Directors AHA, SHC, Scanadu (mobile health), SignalPath (software) 3

4 Leading Causes of Global Death and Disability ( ) -Global Burden of Disease Project, Lancet

5 US ACS Hospitalizations Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI STEMI 1.24 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: million Admissions per year

6 % In-Hosp Mortality Link Between Overall Guidelines Adherence and Mortality Every 10% in guidelines adherence 11% in mortality (OR=0.89, 95% CI: ) <=25% 25-50% 50-75% >=75% Hospital Composite Quality Quartiles -Peterson E et al. JAMA 2006 Adjusted Unadjusted

7 Top 10 NSTE ACS Advances (~25+ yrs) 1. Categorizing by ECG: STE and NSTE ACS 2. Practice guidelines 3. Risk stratification and risk scores 4. ASA and UFH as foundational therapies 5. Troponin to risk stratify AND predict treatment response 6. Glycoprotein IIb/IIIa inhibitors 7. Platelet ADP blockers and other receptor inhibitors 8. Early invasive approach 9. Risk post hospitalization 10. Global academic collaborations 7

8 First Unstable Angina Guidelines 8

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11 Guideline Authoring Principles Evidence-based (see COR/LOE slide) Abstracts are discouraged - must be published within 2 years and cannot be basis for a recommendation Late Breaking Clinical Trials (LBCT) - Should not be used for development of recommendations until published in peerreviewed journals (limited text reference acceptable) Transparent - all relationships with industry are considered during the writing process and published in the final document Collaborative - other organizations are invited as partners, collaborators, authors, endorsers Concordant - guidelines should be consistent across topics unless there is new published evidence to justify a change. When there is overlap, recommendations in disease-based guidelines supersede recommendations in procedure guidelines.

12 Applying Classification of Recommendations and Level of Evidence Class I Class IIa Class IIb Class III Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Benefit Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Risk Benefit No additional studies needed Procedure/Treatment should NOT be performed/administere d SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level A: Level B: Level C: 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 Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated

13 2014 AHA/ACC Guideline for the Management of Patients With Non ST-Elevation Acute Coronary Syndromes Developed in Collaboration with the Society of Thoracic Surgeons and Society for Cardiovascular Angiography and Interventions Endorsed by the American Association for Clinical Chemistry American College of Cardiology Foundation and American Heart Association

14 Prognosis: Early Risk Stratification (cont d) Recommendations COR LOE Additional troponin levels should be obtained beyond 6 hours after symptom onset (see Section 3.4, Class I, #3 recommendation if time of symptom onset is unclear) in patients with normal troponin levels on serial examination I A when changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS. Risk scores should be used to assess prognosis in patients with NSTE-ACS. I A Risk-stratification models can be useful in management. IIa B

15 Anti-Ischemic and Analgesic Medications: Beta-Adrenergic Blockers Recommendations COR LOE Oral beta-blocker therapy should be initiated within the first 24 hours in patients who do not have any of the following: 1) signs of HF, 2) evidence of low-output state, 3) increased risk for cardiogenic shock, or 4) other contraindications to I A beta blockade (e.g., PR interval >0.24 second, second- or third-degree heart block without a cardiac pacemaker, active asthma, or reactive airway disease). In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function, it is recommended to continue beta-blocker therapy with 1 of the 3 drugs proven to reduce mortality in patients with HF: sustained-release metoprolol succinate, carvedilol, or bisoprolol. I C

16 Anti-Ischemic and Analgesic Medications: Beta-Adrenergic Blockers (cont d) Recommendations COR LOE Patients with documented contraindications to beta blockers in the first 24 hours of NSTE-ACS should be re-evaluated to I C determine their subsequent eligibility. It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS. IIa C Administration of intravenous beta blockers is potentially III: harmful in patients with NSTE-ACS who have risk factors Harm for shock. B

17 Anti-Ischemic and Analgesic Medications: Cholesterol Management Recommendations COR LOE High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and no contraindications to I A its use. It is reasonable to obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. IIa C

18 Factors Associated With Appropriate Selection of Early Invasive Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS Immediate invasive (within 2 h) Ischemiaguided strategy Early invasive (within 24 h) Delayed invasive (within h) Refractory angina Signs or symptoms of HF or new or worsening mitral regurgitation Hemodynamic instability Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy Sustained VT or VF Low-risk score (e.g., TIMI [0 or 1], GRACE [<109]) Low-risk Tn-negative female patients Patient or clinician preference in the absence of high-risk features None of the above, but GRACE risk score >140 Temporal change in Tn (Section 3.4) New or presumably new ST depression None of the above but diabetes mellitus Renal insufficiency (GFR <60 ml/min/1.73 m²) Reduced LV systolic function (EF <0.40) Early postinfarction angina PCI within 6 mo Prior CABG GRACE risk score ; TIMI score 2

19 Early Hospital Care Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS Come to our Session on Antithrombotic Therapies in ACS and CAD at 1145AM!

20 Quality of Care and Outcomes for ACS-Use of Performance Measures and Registries Recommendation COR LOE Participation in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and performance measures can be beneficial in improving the quality of NSTE-ACS care. IIa B

21 Thanks for the Opportunity to Visit 21