Update in Acute Coronary Syndromes Hani Jneid, MD, FACC, FAHA Baylor College of Medicine Michael E. DeBakey VAMC

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1 Update in Acute Coronary Syndromes Hani Jneid, MD, FACC, FAHA Baylor College of Medicine Michael E. DeBakey VAMC NAAMA 37 th National Medical Convention September 5 th, 2015

2 Atherosclerosis Coronary Heart Disease (CHD) Acute Coronary Syndromes I. Non-ST Elevation ACS 1. Unstable Angina 2. Non-ST Elevation Myocardial infarction II. ST-elevation Myocardial Infarction Chronic Stable Angina Why are these two syndromes so different?

3 Chronic Stable Angina Acute Coronary Syndromes Stable Plaque Plaque disruption Thrombosis

4 Hospitalizations in the U.S. Due to ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI 1.24 million Admissions per year STEMI 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:

5 Epidemiology Age- and Sex-adjusted Incidence rates of AMI, Yeh R. NEJM 2010

6 Presentation Ischemic Discomfort Acute Coronary Syndrome Working Dx ECG Cardiac Biomarker No ST Elevation Non-ST ACS UA NSTEMI ST Elevation Final Dx Unstable Angina Myocardial Infarction NQMI Qw MI Libby P. Circulation 2001;104:365, Hamm CW, Bertrand M, Braunwald E, Lancet 2001; 358: ; Davies MJ. Heart 2000; 83: Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 1. Reprinted with permission.

7 Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007: HJ mod/adapted- Anderson JL, et al. J Am Coll Cardiol 2007;50:e1 e157, Figure 5.

8 Third Universal Definition of MI The preferred biomarker, overall and for each specific category of MI, is ctn (I or T). If a ctn assay is not available, the best alternative is CKMB (measured by mass assay). Thygesen et al.ehj 2012

9 Third Universal Definition of MI The preferred biomarker, overall and for each specific category of MI, is ctn (I or T). If a ctn assay is not available, the best alternative is CKMB (measured by mass assay). Thygesen et al.ehj 2012

10 Therapies specific to the specific Type of Acute Coronary Syndromes Non-ST Elevation Acute Coronary Syndromes (NSE- ACS) (Unstable Angina; Non-ST Elevation Myocardial Infarction [NSTEMI]). vs. ST-elevation Myocardial Infarction (STEMI) Acute Reperfusion (primary PCI or Fibrinolytics) Early Invasive Strategy (Early coronary angiography [cardiac catheterization], within h or 72 h, and revascularization)

11 45 yo man presented with one day of continuous sharp chest pain, accompanied by constitutional sxs and lower RTI sxs. Initial Troponin 14 ng/dl bedside TTE: global LV dysfcuntion (LVEF 45%).

12 45 yo man presented with one day of continuous sharp chest pain, accompanied by constitutional sxs and lower RTI sxs. Initial Troponin 14 ng/dl bedside TTE: global LV dysfcuntion (LVEF 45%).

13 Thrombus occluding the LAD artery Hani Jneid MD- Aug

14 Aspiration thrombectomy for Patients with STEMI

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16 STEMI LAD occlusion After thrombectomy stent After stent implantation

17 Reperfusion Therapy for Patients with STEMI *Patients with cardiogenic shock or severe heart failure initially seen at a non PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). Angiography and revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.

18 Impact of Time of Presentation on The Care and Outcomes Of AMI Jneid H et al, Circulation 2008 N= 62,814 AMI at 379 hospitals between 07/2000 and 09/ min difference in DTB between regular hours and off-hours

19 Cardiac and Non-Cardiac Conditions that mimic ACSs

20 Cardiac and Non-Cardiac Conditions that mimic ACSs

21 Treatment of Acute Coronary Syndromes MEDICAL THERAPIES Antiplatelet Rx Anticoagulant Rx Anti-Ischemic Rx INVASIVE THERAPIES Coronary angiography PCI Coronary angiography CABG

22 Prasugrel vs. Clopidogrel in Patients with Acute Coronary Syndromes (TRITON TIMI 38) CV death/mi/stroke RCT: Prasugrel vs. Clopidogrel N=13,608 pts; mod/high-risk ACS Scheduled for PCI Duration: 6 to 15 months (14.5 median) Major bleeding Prasugrel benefits: 1. MI (9.7 vs. 7.4%; P<0.001) 2. Urgent TVR (3.7 vs. 2.5%; P<0.001) 3. ST (2.4% vs. 1.1%; P<0.001) Prasugrel adverse effects: 1. More major bleeding (2.4 vs. 1.8%; P = 0.03). 2. More life-threatening bleeding (1.4 vs. 0.9%; P = 0.01) 3. More fatal bleeding (0.4% vs. 0.1%; P = 0.002). Wiviott et al, N Engl J Med 2007;357:2001

23 Prasugrel vs Clopidogrel in Patients with Acute Coronary Syndromes (TRITON TIMI 38) N Engl J Med 2007;357:2001 N O M O R T A L I T Y D I F F E R E N C E S NNT= 46 (primary EP) NNH= 167 (non-cabg TIMI major bleeding)

24 multicenter, double- blind, randomized trial Ticagrelor (180-mg load, 90 mg bid) vs. Clopidogrel (300/600mg load dose, 75 mg qd) N= 18,624 ACS pts N Engl J Med 2009;361:1045

25 9.8 vs. 11.7%, HR 0.84; 95% CI ; P< vs.11.2%, HR % CI , P=0.43 Ticagrelor: more dyspnea, ventricular pauses, and non procedure-related bleeding N Engl J Med 2009;361:1045

26 P2Y 12 Inhibitors

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28 TIMING OF INVASIVE THERAPY for Non-STE ACS

29 Early Invasive vs. Conservative Therapy Angina Rehospitalization Non-fatal MI (mean Follow-Up of 2 yrs) All-cause mortality Bavry AA, et al. J Am Coll Cardiol 2006;48: Reprinted with permission from Elsevier. CI = confidence interval; RR = relative risk.

30 Selection of Initial Rx Strategy: Invasive vs. Conservative

31 Early vs. Delayed Invasive Intervention in Acute Coronary Syndromes N= 3,031 ACS patients - 1:1 randomization ([routine/early 24] vs. [delayed 36 h] invasive strategy) - The primary outcome: 6 mo composite of death/mi/cva - Secondary outcome: 6 mo composite of death/mi/refractory ischemia - Shamra, et al. N Engl J Med 2009;360:2165.

32 N Engl J Med 2009;360:2165 Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients

33 Revascularization in ACS patients with CKD

34 Influence of Renal Function on the Effects of Early Revascularization in Non-ST- Elevation Myocardial Infarction The SWEDEHEART registry N= 23,262 patients with NSTE-ACS with available Cr and < 80 yo Pts who had coronary angiography but no revascularization within 14 d MED tx Pts with mild-mod CKD have associated lower mortality with early revascularization. Severe or more advanced CKD is associated have poor prognosis that does not seem to be improved with invasive therapy. Szummer K, et al. Circulation. 2009;120:

35 Revascularization in ACS patients with CKD 2012 ACC/AHA Guidelines I IIa IIb III

36 Initial Invasive Therapy and Early Revascularization Impart Survival Benefit in Appropriately-selected Patients with Severe Chronic Kidney Disease Henry Huang, Hani Jneid, et al Aggregate data meta-analyses to evaluate the comparative effectiveness of the following strategies in patients with ACS and various stages of CKD: (a) initial invasive vs. conservative strategy (b) early revascularization vs. initial medical Rx H Huang - H Jneid et al. IJC 2014

37 Model Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper ratio limit limit Z-Value p-value Chertow et al. (2000) Keeley et al. (2003) Hemmelgarn et al. (2004) Szummer et al. (2009) Random Early Revascularization vs. Initial Medical Therapy after ACS: 1-year Mortality Meta Model Analysis Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper ratio limit limit Z-Value p-value Chertow et al. (2000) Hemmelgarn et al. (2004) Szummer et al. (2009) Random Meta Model Analysis Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper ratio limit limit Z-Value p-value Chertow et al. (2000) Hemmelgarn et al. (2004) Szummer et al. (2009) Random Favors Revascularization Favors Revascularization Medical Therapy Medical Therapy Favors Revascularization Medical Therapy Meta Analysis Group egfr Statistics for each study Odds ratio and 95% CI Odds Lower Upper ratio limit limit Z-Value p-value egfr egfr egfr ESRD only Favors Revascularization Medical Therapy Meta Analysis a possible gradient effect?

38 How to treat an ASC patient in 2015?

39 68 yo man presented with 45 min of chest heaviness at rest, accompanied with diaphoresis and SOB. He has DM, underwent prior CABG, and was receiving ASA and lovastatin. At ED, he became symptom-free after 2 SL NTG.

40 68 yo man presented with 45 min of chest heaviness at rest, accompanied with diaphoresis and SOB. He has DM, underwent prior CABG, and was receiving ASA and lovastatin. At ED, he became symptom-free after 2 SL NTG.

41 Case Illustration Antiplatelet Rx? ASA t i clopidine Clopirogrel Prasugrel Ti cagrelor G P IIbIIIa

42 Case Illustration Antiplatelet Rx? ASA t i clopidine Clopirogrel Prasugrel Ticagrelor G P IIbIIIa

43 Case Illustration Anticoagulant Rx? Unfractionated Heparin Enoxaparin Bivalirudin Fondaparinux

44 Case Illustration Anticoagulant Rx? Unfractionated Heparin Enoxaparin Bivalirudin Fondaparinux

45 Case Illustration Anti-Ischemic Rx (in-hospital) PO metoprolol tartrate NTG IV Lisinopril Rosuvastatin (NSAIDs stopped)

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47 Case Illustration (Discharge) ASA 81 mg po qd, indefinitely Ticagrelor 90 mg po bid, at least 12 mo Metoprolol 50 mg qd (at least 3 yrs +) Lisinopril 20 mg po qd Rosuvastatin 40 mg po qhs Metformin 1000 mg po bid BP < 150/90 mmhg Complete tobacco cessation Cardiac rehabilitation

48 Typical Progression of Coronary Atherosclerosis Hani Jneid MD- Aug

49 Acute Coronary Syndrome

50 Case Illustration (what do at 6-week FU?) BP < 150/90 mmhg Complete tobacco cessation. No exposure to environmental tobacco smoke. High-intensity Statin Physical activity goal: At least 30 minutes, 7 days per week (minimum 5 days per week) / Cardiac Rehab AHA Diet BMI kg/m2 - Waist circumference: < 40 inches (men) his target HbA1C < 7% Influenza vaccination No depression

51 Cardiac Rehabilitation

52 2011 Secondary Prevention GLs Cardiac Rehabilitation

53 Post hospitalization Plan of Care STEMI Guidelines 2013 I IIa IIb III Exercise-based cardiac rehabilitation/secondary prevention programs are recommended for patients with STEMI.

54 PERFORMANCE MEASURES

55 Thank you