Recognizing the High Risk NSTEMI Patient for Early Appropriate Therapy

Recognizing the High Risk NSTEMI Patient for Early Appropriate Therapy

Learning Objectives Learn to recognize the high risk patient Discuss effective management of a high risk NSTEMI patient Review CCS Focused Antiplatelet Guidelines for NSTEMI

Disclosure of Commercial Support This program has received financial support from AstraZeneca and Bayer in the form of an educational grant, and has been co developed in conjunction with the Canadian Association of Emergency Physicians (CAEP). Potential for conflict(s) of interest: Dr. Bainey, Dr. Ghosh and Dr. Sookram have all received payment from AstraZeneca. AstraZeneca licenses a product that will be discussed in this program: Brilinta (ticagrelor)

Mitigating Potential Bias Potential Biases are acknowledged and are mitigated by presenting data supported by national and international guidelines, and as follows: Information presented is evidence based Recommendations made are evidence or guidelines based rather than personal recommendations of the presenter Material has been developed and reviewed by an Educational Committee

Faculty/Presenter Disclosure Faculty: Sunil Sookram, MD, FRCPC Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: AstraZeneca, Hoffman La Roche Consulting Fees: None Other: None

Faculty/Presenter Disclosure Faculty: Kevin Bainey, MD, MSc, FRCPC Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: AstraZeneca, Bristol Myers Squibb, Merck, Pfizer Consulting Fees: None Other: None

Faculty/Presenter Disclosure Faculty: Indy Ghosh, MD, CCFP (EM) Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: AstraZeneca, BI, BMS/Pfizer, Bayer, Sanofi Aventis Consulting Fees: None Other: None

Case Study

Case Study: Mr. Chan 77 year old man hx HTN, NIDDM Episodic epigastric pain x 1 day, 5 6 bouts, longest 30 min with diaphoresis, now pain free Your Thoughts? How will you evaluate Mr. Chan? Is he a high risk patient? No known CAD Smokes 50 yrs Ramipril, metformin VS normal, exam noncontributory

Mr. Chan: Admission ECG

Mr. Chan: Admission Tests ECG: normal Biomarkers essential hstnt = 115 ng/l Pain returns in the ED Troponin Interpretation < 14 ng/l Normal 15 109 ng/l Borderline elevation > 110 ng/l Clear elevation

Is Mr. Chan a High Risk Patient? Recurrent angina or ischemia at rest or with low level activities Elevated cardiac biomarkers (TnT or TnI) New or presumably new ST depression or transient ST elevation or T wave inversion New LBBB or sustained ventricular tachycardia High risk findings from non invasive testing Hemodynamic instability Sustained ventricular tachycardia Renal dysfunction, T2DM, PCI within 6 months, prior CABG High risk score (e.g. TIMI, GRACE) Reduced LVEF (< 40%) Fitchett DH et al. CJC 2011;27:S387 S401; Kumar A et al. Mayo Clinic Proceedings Oct 2009; 84(10):917 38

Risk Scores: TIMI and GRACE TIMI GRACE HISTORY PRESENTATION GRACE = Global Registry of Acute Coronary Events TIMI = Thrombolysis in Myocardial Infarction Age Hypertension Diabetes Smoking Cholesterol Family history Documented CAD Severe angina Aspirin within 7 days Elevated markers ST segment deviation Age Heart rate Systolic BP Elevated creatinine Heart failure Cardiac arrest Elevated markers ST segment deviation Antman EM, et al. JAMA 2000; 284(7):835 42; D'Ascenzo F, et al. Contemp Clin Trials 2012; 33:507 14

Risk Factor Mr. Chan s TIMI Score Age 65 1 ASA use in past 7 days 0 2 angina episodes in last 24 hrs 1 ST changes 0.5 mm on admission ECG 0 Elevated serum cardiac markers 1 Known CAD (coronary stenosis >= 50%) 0 3 risk factors for CAD 0 Total Score 3 History, ECG and troponin should be evaluated before TIMI % Risk at 14 days* 40 30 20 10 0 5 8 13 20 26 41 0,1 2 3 4 5 6,7 TIMI score *All cause mortality, new or recurrent MI or severe recurrent ischemia requiring urgent revascularization Apps available for iphone, ipad and ipod Antman EM, et al. JAMA 2000; 284(7):835 42; D'Ascenzo F, et al. Contemp Clin Trials 2012; 33:507 14

Mr. Chan s GRACE Score Online GRACE RISK calculator GRACE 2.0 available as a free app D'Ascenzo F, et al. Contemp Clin Trials 2012; 33:507 14

How Will You Handle Mr. Chan? a) Refer to cardiology without starting OAP therapy b) Refer to cardiology after starting DAPT (ticagrelor + ASA) c) Refer to cardiology after starting DAPT (clopidogrel + ASA)

OAP in High Risk Patients a) Meta analysis, n=135,000 b) OAP is superior in preventing vascular events vs. control (p<0.0001) in all 5 groups Previous MI Acute MI Previous stroke/transient ischemic attack Acute stroke Other high risk c) Unstable angina trials, n=5031 5% difference, NNT=20 Antithrombotic Trialists' Collaboration. BMJ 2002;324:71

Comparison of Ticagrelor with Clopidogrel Primary Endpoint: CV Death, MI or Stroke Cumulative Incidence (%) NSTEMI ACS (moderate to high risk) N = 18,624 13 12 11 10 9 8 7 6 5 4 3 2 1 0 Clopidogrel MI 16% p=0.005 CV death 21% p=0.001 HR 0.84 (95% CI 0.77 0.92), p < 0.001 Ticagrelor 0 60 120 180 240 300 360 11.7 9.8 DAYS Major bleeding NS PLATO: Wallentin L et al. NEJM 2009;361:1045 57

QUESTIONS? Enter questions in the text box on www.imedicus.ca Text questions to 514 400 2504 Tweet @imedicus_live Email questions to questions@imedicus.ca. IMPORTANT: When emailing, please enter question in the subject line only

CCS Guidelines Early Treatment with P2Y 12 Inhibitor in Moderate to High Risk NSTEMI Patient* ASA 81 mg daily Indefinite therapy PCI CABG Surgery Medical Therapy (no CABG, no PCI) Add ticagrelor for 12 months Add ticagrelor for 12 months Add ticagrelor for 12 months Patient ineligible for ticagrelor Add clopidogrel for 12 months (consider 150 mg/day for 6 days if PCI performed) Tanguay et al. Can J Cardiol 2013;29:1334 45

OAP in ACS: The World Beyond CCS CADTH report conclusions based on NICE, ESC, ISCI, AAPI and FDA documents and guidelines (CCS Guidelines not included): NSTEMI and STEMI: prasugrel and ticagrelor more efficacious than clopidogrel Clopidogrel + ASA Prasugrel + ASA Ticagrelor + ASA prevent ischemic events and stent thrombosis in NSTEMI and STEMI prevent stent thrombosis in PCI prevent thrombosis in ACS Antiplatelets for ACS: CADTH report 2012. PLOS ONE 2014;19(3)

PCI Improves Outcomes TACTICS ACS (TIMI 18) PCI vs. Conservative management Primary endpoint: Composite of death, nonfatal MI or hospitalization for ACS Primary endpoint at 6 months: OR 0.78, p=0.025 Death or MI at 6 months: OR 0.74, P<0.05 In Canada, the majority of high risk NSTEMI get early cardiac catheterization. Patients with undetermined risk should be observed for a min of 12 hrs so their actual risk can be assessed. Fitchett DH et al. CJC 2011;27:S387 S401; Cannon C et al. Circulation 2000;102:2672

Early PCI (< 24 hrs) Improves Outcomes Coronary angiography and intervention 24 hrs vs. 36 hrs N=3031 Primary outcome: composite of death, MI or stroke at 6 months Early vs. late: HR 0.85; P=0.15 In 1/3 pts at high risk: 0.65 Secondary outcome: death, MI or refractory ischemia at 6 months Early vs. late: HR 0.72; P=0.003 Damman et al. Angiography within 2 days vs. later no benefit for 5 year CV death or MI rates Mehta SR et al. NEJM 2009 May 21;360:2165 75; Damman P et al. JACC 2012;5:191 9

Will You Anticoagulate Mr. Chan? Cochrane analysis: in UA/NSTEMI, heparins reduced MI risk compared with placebo RR 0.4, NNT 33 a trend towards more major bleeds, RR=2.05 Consider bleeding risks CRUSADE risk score hemodynamic instability risk of ischemic events renal insufficiency PCI/catheterization in the past 24 hrs femoral access site use of gp IIb/IIIa inhibitors therapy with ASA and/or OAP Fitchett DH et al. CJC 2011;27:S387 S401; Andrade Castellanos CA. Cochrane Database Syst Rev 2014;6:CD003462

Anticoagulation for Mr. Chan NICE Pathway: Low bleed risk fondaparinux PCI likely or Cr>265 UFH (confirm creatinine clearance and add units) High bleed risk monitor renal function and modify dose Carefully consider choice and dose of antithrombin if high bleed risk plus any of the following: advanced age known bleeding complications renal impairment low body weight Fitchett DH et al. CJC 2011;27:S387 S401; Andrade Castellanos CA. Cochrane Database Syst Rev 2014;6:CD003462

The Role of Oral Anticoagulants in ACS Is Uncertain Meta analysis: NOAC + DAPT N=30,866 STEMI or NSTEMI in last 7 14 days MACE: composite of all cause mortality, MI or stroke Bleeding: composite of major and non major bleeding requiring medical attention NOAC + ASA vs. ASA MACE: HR 0.70 Bleeding HR 1.79 NOAC + DAPT vs. DAPT (Clopidogrel + ASA) MACE: HR 0.87 Bleeding HR 2.34 Oldgren J et al. Eur Heart J 2013;34(22):1670 80, Singh D et al. Clev Clin J Med 2014;81:103 14

Case Study: Evaluation/DDx Audience Question Do you have ACS Order Sets in your ED that outline OAP treatment initiation for high risk NSTEMI patients? a) Yes b) No

QUESTIONS? Enter questions in the text box on www.imedicus.ca Text questions to 514 400 2504 Tweet @imedicus_live Email questions to questions@imedicus.ca. IMPORTANT: When emailing, please enter question in the subject line only

Key Take Away Points Identify the high risk ACS patient early Be confident about initiating treatment Early invasive treatment (< 24 hrs) improves outcomes

Thank You! Content for this program was developed by the following steering committee members: Dr. Anil Chopra, Dr. Jean Grégoire, Dr. Anil Gupta, Dr. Eddy Lang and Dr. Robert Welsh COMMERCIAL SUPPORT ACKNOWLEDGEMENT: THIS EDUCATIONAL ACTIVITY IS SUPPORTED BY AN INDEPENDENT EDUCATIONAL GRANT FROM ASTRAZENECA and BAYER CANADA