2015 ESC Guidelines for the Management of ACS in Patients presenting without Persistent ST-Elevation

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1 ESC/Saudi Heart Association Joint Meeting Dammam, November 14-15, ESC Guidelines for the Management of ACS in Patients presenting without Persistent ST-Elevation Francesco Cosentino, MD, PhD, FESC Chair of Cardiovascular Medicine Unit of Cardiology Karolinska University Hospital Stockholm

2 2 Conflicts of Interest Advisory board/speaker AstraZeneca Roche BMS MSD Abbott Bayer Research funding Karolinska Institute Swedish Heart & Lung Foundation European Foundation for Study of Diabetes (EASD)

3 3

4 4 What is new (1) New diagnostic algorithm using high-sensitivity cardiac troponin Guidance on cardiac rhythm monitoring Antithrombotic treatment Timing of P2Y12 inhibitor administration in patients scheduled for early invasive strategy (pretreatment) Duration of dual antiplatelet therapy Antiplatelet agents and CABG (Web addenda) Managing oral antiplatelet agents in patients requiring long-term oral anticoagulants (vitamin K antagonists, non-vitamin K antagonist oral anticoagulants) New agents: cangrelor and vorapaxar Management of acute bleeding events (Web addenda) In patients on antiplatelet agents, vitamin K antagonists, non-vitamin K antagonist oral anticoagulants

5 5 What is new (2) Revascularization Modified classification of the characteristics mandating the indication/timing of invasive strategy Radial approach Technical aspects and challenges of revascularization in NSTE-ACS (PCI and CABG [Web addenda]) Section on gender (Web addenda) Special populations and conditions (Web addenda) NSTE-ACS and atrial fibrillation NSTE-ACS and chronic analgesic or anti-inflammatory treatment NSTE-ACS and non-cardiac surgery Secondary prevention Lipid lowering beyond statins «Questions and Answers» companion manuscripts

6 6 Initial assessment of patients with suspected acute coronary syndromes Echo

7 0 h/1 h Rule-in and rule-out algorithms using highsensitivity cardiac troponins (hs-ctn) assays in patients presenting with suspected NSTEMI Very Low Low or and No 0-1h High or 0-1h Negative predictive value of pts meeting rule out criteria >98% for acute MI Positive predictive value 75-80% for acute MI Cut-offs for «rule-in» and «rule-out» assay specific

8 8 Clinical implications of high-sensitivity cardiac troponin assays (1)

9 9 Cardiac troponins

10 Unstable angina vs NSTEMI UA NSTEMI Acute cardiomyocyte necrosis Risk of death/major arrhythmias -/+ +++ Derive less benefit from - intensified antiplatlet therapy -/ early revascularization -/+ +++ Small proportion of UA pts this slide is dealing with the issue of UA in the era of hs ctn assays. compared to NSTEMI The introduction of resulted

11 11 Recommendations for rhythm monitoring in pts with suspected NSTE-ACS Intermediate or high risk for cardiac arrhythmia One or more of the following; - haemodynamically unstable - major arrhythmias - LVEF <40% - failed reperfusion - additional critical coronary stenoses of major vessels - complications of PCI Low risk for cardiac arrhythmia None of the above Although early revasc, antithromb drugs, bb reduced incidence of lif-threa

12 Recommendations for platelet inhibition in NSTE-ACS Recommendations Oral antiplatelet therapy Aspirin is recommended for all patients without contra-indications at an initial oral loading dose c of mg (in aspirin-naïve patients) and a maintenance dose of mg daily long-term regardless of treatment strategy. A P2Y 12 inhibitor is recommended to reduce recurrent ischemic events, in addition to aspirin, for 12 months unless there is excessive risk of bleeds. Ticagrelor (180 mg loading dose, 90 mg twice daily) is recommended, in the absence of contraindications d, for all patients at moderate- to high-risk of ischaemic events (e.g. elevated cardiac troponins), regardless of initial treatment strategy and including those pretreated with clopidogrel (which should be discontinued when ticagrelor is started). Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended in patients who are proceeding to PCI if no contraindication. d Clopidogrel ( mg loading dose, 75 mg daily dose) is recommended for patients who cannot receive ticagrelor or prasugrel or who require oral anticoagulation. P2Y 12 inhibitor administration for a shorter duration of 3 6 months after DES implantation may be considered in patients deemed at high bleeding risk. It is not recommended to administer prasugrel in patients in whom coronary anatomy is not known. Class a I I I I I IIb III Leve l b A A B B B A B

13 Timing of P2Y 12 inhibitor initiation Controversial issue As the optimal timing of ticagrelor or clopidogrel administration in NSTE-ACS patients scheduled for an invasive strategy has not been adequately investigated, no recommendation for or against pretreatment with these agents can be formulated. Based on the ACCOAST results, pretreatment with prasugrel is not recommended.

14 Duration of dual antiplatelet therapy Recommendations for platelet inhibition in NSTE-ACS (continued) Recommendations Class a Level b Long-term P2Y 12 inhibition P2Y 12 inhibitor administration in addition to aspirin beyond 1 year may be considered after careful assessment of the ischaemic and bleeding risks of the patient. General recommendations A proton pump inhibitor in combination with DAPT is recommended in patients at higher than average risk of gastrointestinal bleeds (i.e. with a history of gastrointestinal ulcer/haemorrhage, anticoagulant therapy, chronic NSAID/corticosteroid use or two or more among age 65 years, dyspepsia, gastro-oesophageal reflux disease, Helicobacter pylori infection, and chronic alcohol use). DAPT has been recommended for 1 year over aspirin alone irrespective of revasc strategy, stent type (CURE). While TRITON and Plato have demonstrated the superiority of pra & tica DAPT regimen over clopi. IIb I A B

15 META-ANALYSIS OF TRIALS EVALUATING PROLONGED DAPT FOLLOWING MI Trial Subgroup /Population N Drug Duration (months) MACE Events Bleeding EP CHARISMA Stable prior MI (mean 24 mo.) 3846 Clopi GUSTO mod/severe PRODIGY PCI for ACS 1465 Clopi 6 vs TIMI major ARCTIC- Interruption PCI for ACS (excluded STEMI) 323 Clopi or Pras 12 vs STEEPLE major DAPT PCI for MI 3576 Clopi or Pras 12 vs GUSTO mod/severe DES-Late PCI for ACS 3063 Clopi 12 vs TIMI major PEGASUS TIMI-54 Stable prior MI (median 20 mo.) Ticag TIMI major Total of rand trials comparing DAPT with asp alone for >1 y in high risk with prior MI Abbreviations: Clopi: clopidogrel; Pras: prasugrel; Ticag: ticagrelor > pts were followed for a mean of 31 months J. Udell (Toronto, CA) FP3913

16 META-ANALYSIS: INDIVIDUAL CV AND BLEEDING ENDPOINTS Event Rate (%) Event Rate (%) HR 0.78 P = HR 0.85 P = HR 0.70 P = Extended DAPT HR 0.81 P = Aspirin Alone HR 0.50 P = MACE CV Death MI Stroke Stent Thrombosis (Def/Prob) HR 1.73 P = P = NS P = NS HR 1.05 P = NS HR 0.92 P = NS Major Bleeding ICH Fatal Bleeding Non-CV Death All-Cause Death Ext DAPT decreased the risk of MACE compared with aspirin alone, reduced CV death with no increase in non -CV death J. Udell (Toronto, CA) FP 3913

17 17 Risk stratification for the selection of treatment strategies (2011: primary/ secondary high-risk criteria) The selection of the optimal timing of coro and revasc should be guided by individual risk stratif

18 Therapeutic strategy Risk Stratification Selection of NSTE-ACS treatment strategy Symptoms Onset First medical contact -> NSTE-ACS diagnosis PCI center EMS or Non-PCI center Very high Immediate transfer to PCI center Very high High Same day transfer High Intermediate Transfer Intermediate Low Transfer Optional Low Immediate invasive (<2hr) Early invasive (<24hr) Invasive (<72hr) Non-invasive testing if appropriate Lowerrisk shorter fewer 1 criterion recurrent known ischemia max delay

19 19 Minimazing Adverse Haemorrhagic Events by Transradial Access Site. MATRIX Co-primary composite outcomes at 30 days All-cause mortality, MI, stroke N=8404 NSTE-ACS + STEMI Radial vs. femoral All-cause mortality, MI, stroke, or BARC 3 or 5 bleeding Valgimigli M et al. Lancet. 2015;385: Bleeding academic res consortium Speaker

20 Radial vs femoral meta-analysis RR (95% CI) P Non-CABG major bleeeds Death, MI, or stroke All cause mortality MI Stroke N> Valgimigli M et al. Lancet. 2015;385:

21 21 Radial approach It is recommended that centres treating ACS patients implement a transition from transfemoral to transradial access. Proficiency in the femoral approach should be maintained (e.g. for IABP insertion and structural as well as peripheral procedures)

22 22 Drug-eluting stents ZEUS* DES use in pts at high risk of bleeding or thrombosis has not been prospectively stu *Valgimigli M et al. J Am Coll Cardiol 2015;65:

23 Major Adverse Cardiovascular Events (Death, MI or TVR) ZEUS zotarolimuseluting vs BMS in uncertain DES candidates BMS: 22.1% E-ZES: 17.5% Valgimigli M et al. J Am Coll Cardiol 2015;65: N=1606 N=826 HBR DAPT duration based on pts characteristics allowed for 1-month Endeavour sprint biocompatiblefast eluting polymer DES+tailored DAPT 24% at 1 year HR 0.76 p:

24 Secondary Endpoints Myocardial Infarction BMS: 8.1% E-ZES: 2.9% Valgimigli M et al. J Am Coll Cardiol 2015;65: Target Vessel Revascularization BMS: 10.7% E-ZES: 5.9% HR 0.33 p < HR 0.49 p: Definite or Probable Stent Thrombosis BMS: 4.1% E-ZES: 2.0% Death for all causes BMS: 17.3% E-ZES: 15.8% HR 0.41 p: HR 0.91 p: 0.57

25 Biolimus-Coated vs. Bare-Metal Coronary Stents in High Bleeding Risk Patients Philip Urban, Alexandre Abizaid, Ian T. Meredith, Stuart J. Pocock, Didier Carrié, Christoph Naber, John Gregson, Samantha Greene, Hans Peter Stoll and Marie-Claude Morice for the LEADERS FREE Investigators NEJM published online October 14, 2015 Courtesy of P. Urban

26 LEADERS FREE Trial Design Prospective, double-blind randomized (1:1) trial 2466 High bleeding risk (HBR) PCI patients BioFreedom DCS vs. Gazelle BMS DAPT mandated for 1 month only, followed by long-term SAPT Primary safety endpoint: Composite of cardiac death, MI, definite / probable stent thrombosis at 1 year (non-inferiority then superiority) Primary efficacy endpoint: Clinically-driven Target Lesion Revasc at 1 year (superiority) DCS: drug coated stent

27 Cumulative Percentage with Event Primary Safety Endpoint (Cardiac Death, MI, ST) % % 9 9.4% 6 3 p = for superiority Number at Risk DCS BMS Days 390 days chosen for assessing primary EP to capture potential events driven by the 360 day FU contact Urban et al NEJM 2015

28 Cumulative Percentage with Event Primary Efficacy Endpoint (Clinically-Driven TLR) % % 6 5.1% 3 0 p for superiority < Number at Risk DCS BMS Days 390 days chosen for assessing primary EP to capture potential evens driven by the 360 day FU contact Target Lesion Revasc Urban et al NEJM 2015

29 Time from PCI/ACS Special population NSTE-ACS patients with OACs for non-valvular atrial fibrillation Management strategy after PCI Medically managed /CABG Bleeding risk Low to intermediate (e.g. HAS-BLED = 0 2) High (e.g. HAS-BLED 3) 0 4 weeks 6 months Triple therapy O A C Dual therapy b Triple or dual therapy a O A C Dual therapy b O C or A Dual therapy b O C or A 12 months O C or A Lifelong O Monotherapy c DES DES/BMS? Oral anticoagulation O A ASA mg daily C (VKA or NOACs) Clopidogrel 75 mg daily a Dual therapy with OAC and clopidogrel may be considered in selected patients (low ischaemic risk). b aspirin as an alternative to clopidogrel may be considered in patients on dual therapy (i.e., oral anticoagulation plus single antiplatelet) Triple therapy may be considered up to 12 months in patients at very high risk for ischaemic events. c Dual therapy with oral anticoagulation and an antiplatelet agent (aspirin or clopidogrel) beyond one year may be considered in patients at very high risk of coronary events. In patients undergoing coronary stenting, dual antiplatelet therapy may be an alternative to triple or dual therapy if the CHA2DS2-VASc score is 1 (males) or 2 (females). To deal with the issue of oral antiplt agents in pts requiring OAC who cannot tolerate long term exposure to DAPT

30 40 cases each No reference Link to the dedicated sections of the GL Help to implement GL in daily practice 30 European Heart Journal doi: /eurheartj/ehv409 European Heart Journal doi: /eurheartj/ehv407 European Heart Journal doi: /eurheartj/ehv408

31 European Heart Journal 2015 doi: /eurheartj/ehv320

32 32 ESC Pocket Guidelines application available! European Heart Journal (2015) doi: /eurheartj/ehv319

33 Thank you for your participation

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35 35 Clinical implications of high-sensitivity cardiac troponin assays (2)

36 Recommendations for long-term management post NSTE-ACS Recommendations (for the recommendations on antithrombotic Class a Level b treatment see sections and 5.3.3). d It is recommended to advise all patients on life style changes (including smoking cessation, regular physical activity and a healthy diet). I A It is recommended to start high-intensity statin therapy as early as possible, unless contraindicated, and maintain it long-term. I A An ACE inhibitor is recommended in patients with LVEF 40%, or heart failure, hypertension or diabetes, unless contraindicated. An ARB provides an alternative, particularly if ACE inhibitors are not tolerated. I A Beta-blocker therapy is recommended in patients with LVEF 40%, unless contra-indicated. I A

37 Recommendations for long-term management post NSTE-ACS (continued) Recommendations (for the recommendations on antithrombotic Class a Level b treatment see sections and 5.3.3). d Mineralocorticoid receptor antagonists, preferably eplerenone, are recommended in patients with LVEF 35% and either heart failure or diabetes after NSTE-ACS but no significant renal dysfunction or hyperkalaemia. c I A A diastolic blood pressure goal of <90 mmhg is recommended (<85 mmhg in diabetic patients). I A Participation in a well-structured cardiac rehabilitation program to modify lifestyle habits and increase adherence to treatment should be considered. In patients with LDL-cholesterol 70 mg/dl ( 1.8 mmol/l) despite a maximally tolerated statin dose, further reduction in LDL-cholesterol with a non-statin agent e should be considered. IIa IIa A B A systolic blood pressure goal of <140 mmhg should be considered. IIa B e At the time of finalizing these guidelines this recommendation applies only to ezetimibe

38 Components of Safety Endpoint % p = 0.19 p = 0.01 p = 0.70

39 Strategies to reduce the bleeding risk Roffi M et al. European Heart Journal doi: /eurheartj/ehv320

40 Major Adverse Cardiovascular Events (Death, MI or TVR) Valgimigli M et al. J Am Coll Cardiol 2015;65: BMS: 29.0% E-ZES: 22.6% N=1606 N=826 HBR 26% HR 0.74 p:

41 Secondary Endpoints Myocardial Infarction BMS: 10.4% E-ZES: 3.5% Valgimigli M et al. J Am Coll Cardiol 2015;65: Target Vessel Revascularization BMS: 11.4% E-ZES: 5.9% HR 0.33 p < HR 0.49 p: Definite or Probable Stent Thrombosis BMS: 6.2% E-ZES: 2.6% Death for all causes BMS: 17.3% E-ZES: 15.8% HR 0.41 p: HR 0.91 p: 0.57

42 0 h/1 h Rule-in and rule-out algorithms using highsensitivity cardiac troponins (hs-ctn) assays in patients presenting with suspected NSTEMI 42