Updates in Acute Coronary Syndromes Management Mohammad Zubaid, MB, ChB, FRCPC, FACC Professor of Medicine, Kuwait University Head, Division of Cardiology Mubarak Alkabeer Hospital Kuwait The 1st Kuwait-North American update in Internal Medicine 4th Medical Scientific Conference – Mubarak Alkabeer Hospital February 7, 2014 – Jumeirah hotel, Kuwait

From plaque formation to progression to clinical manifestations STABLE No symptoms Silent ischemia Stable angina Slow Risk factor Atherosclerosis progression UNSTABLE Unstable angina NSTEMI STEMI Sudden cardiac death Accelerated Progression Atherothrombosis

Distribution of ACS type in Kuwait Discharge diagnosis 2534 patients

Gulf COAST 2012 Kuwait population STEMI (288) n (%) Age (Mean ±SD) 56.7±13.3 Female 61 (21) Hypertension 145 (50) Diabetes 152 (53) Smoking 164 (57) Prior MI 41 (14) Prior PCI 25 (9) Prior CABG 7 (2) Prior TIA Prior stroke 19 (7)

Pooled analysis of the short-term results from 23 randomized trials comparing primary PCI and fibrinolytic therapy in 7739 patients Figure 1. Pooled analysis of the short-term results from 23 randomized trials comparing primary PCI and fibrinolytic therapy in 7739 total patients. Data from Reference 13. Data vary slightly from Reference 13 because of presentation of relative risks (RRs) rather than ORs. Stone G. Circulation 2008;118:538-551

Primary PCI Recommendations Class Level Indications for primary PCI Primary PCI is the recommended reperfusion therapy over fibrinolysis if performed by an experienced team within 120 min of FMC I A Primary PCI is indicated for patients with severe acute heart failure or cardiogenic shock, unless the expected PCI related delay is excessive and the patient presents early after symptom onset. B Steg et al, EHJ 2012;33:2569-2619

Periprocedural antithrombotic medications in primary PCI Recommendations Class Level Antiplatelet therapy Aspirin oral or i.v. (if unable to swallow) is recommended I B An ADP- receptor blocker is recommended in addition to aspirin. Option are: A Prasugrel in clopidogrel-naive patients, if no history of prior stroke/TIA, age <75 years. Ticagrelor Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated C Steg et al, EHJ 2012;33:2569-2619

Fibrinolytic therapy Recommendations Class Level I A IIa B Fibrinolytic therapy is recommended within 12 h of symptom onset in patients without contraindications if primary PCI cannot be performed by an experienced team within 120 min of FMC I A In patient presenting early (<2 h after symptom onset ) with large infarct and low bleeding risk, fibrinolysis should be considered if time from FMC to balloon inflation is >90 min IIa B If possible, fibrinolysis should start in the Prehospital setting A fibrin – specific agent (tenecteplase, alteplase, reteplase) is recommended ( over non – fibrin specific agents) Oral or i.v. aspirin must be administered Clopidogrel is indicated in addition to aspirin Steg et al, EHJ 2012;33:2569-2619

PCI post lysis Recommendations Class Level Transfer to a PCI capable center following fibrinolysis Is indicated in all patients after fibrinolysis I A Interventions following fibrinolysis Rescue PCI is indicated immediately when fibrinolysis has failed (< 50% ST- segment resolution at 60 min). Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis. B Steg et al, EHJ 2012;33:2569-2619

Prehospital and in-hospital management Reperfusion stratergies within 24 h of FMC STEMI diagnosis Primary PCI capable center EMS or non primary-PCI capable center Preferably < 60 min PCI possible <120 min? Immediate transfer to PCI center Primary - PCI Yes No Preferably ≤ 90 min (≤ 60 min in early presenters) Preferably ≤ 30 min Rescue PCI Immediate transfer to PCI center Immediately No Successful fibrinolysis Immediate fibrinolysis Yes Preferably 3-24 h Coronary angiography Steg et al, EHJ 2012;33:2569-2619

Important treatment goals in the management of STEMI Stages Target Preferred for FMC to ECG and diagnosis ≤ 10 min Preferred for FMC to fibrinolysis (FMC to needle) ≤ 30 min Preferred for FMC to primary PCI (door to balloon) in primary PCI hospitals ≤ 60 min Preferred for FMC to primary PCI in hospitals without cath facility ≤ 90 min (≤ 60 min if early presenter with large area at risk) if this target cannot be met, consider fibrinolysis Acceptable for primary PCI rather than fibrinolysis ≤ 120 min (≤ 90 min if early presenter with large area at risk) if this target cannot be met, consider fibrinolysis Preferred for successful fibrinolysis to angiography 3-24 hours From the previous algorithm you can see that there are some stages/timelines that are highlighted. Steg et al, EHJ 2012;33:2569-2619

Components of delay in STEMI Symptom onset FMC Diagnosis Reperfusion therapy ≤ 10 min Patient delay ………..……………….... ………..………………......... ………..………………... System delay ………..………………................. Time to reperfusion therapy Wire passage in culprit artery (primary PCI) Start of lysis Steg et al, EHJ 2012;33:2569-2619

Reperfusion in eligible patients Per country Bahrain (n= 119) UAE (n= 129) Oman (n= 315) Kuwait (n=259) 29 40 0.3 6 PPCI (%) 58 49 92 86 Lysis (%) 13 11 7.7 8 Shortfall (%)

Reperfusion in eligible patients Kuwait Rest of Hospital (n= 203) Adan Hospital (n=56) 27 PPCI (%) 93 64 Lysis (%) 7 9 Shortfall (%)

Was reperfusion administered in time?

Reperfusion Timeline Thrombolysis in Kuwait Rest of Hospital (n= 188) Adan Hospital (n=37) Thrombolysis 41 34 Median D2NT (min) 36 43 D2NT ≤30 min (%)

Primary PCI experience Adan Hospital November 13 – December 30, 2013 Distribution of timeline

Primary PCI experience Adan Hospital November 13 – December 30, 2013 Distribution of timeline during and after normal working hours During working hours 14 patients After working hours 45 patients Door to ECG 5 7 ECG to cardiology notification 11 6 Cardiology response time 4 3 Door to balloon time 51 62 Door to balloon ≤60 minutes 71% 53% Door to balloon ≤90 minutes 93% 89%

Primary PCI experience Mubarak Alkabeer Hospital November 13 – December 30, 2013 Held off for two weeks in the middle Distribution of timeline

Adan (33 patients) MKH (24 patients) Primary PCI experience MKH vs. Adan Hospital November 13 – December 30, 2013 Distribution of timeline (values in mean) Adan (33 patients) MKH (24 patients) Symptom onset to ER arrival 205 124 Door to ECG 7 18 ECG to cardiology notification 9 20 Cardiology response time 4 3 Door to balloon time 64 111 Door to balloon ≤60 minutes 48% Door to balloon ≤90 minutes 85% 15% Door to balloon ≤120 minutes 97% 65%

Components of delay in STEMI Symptom onset FMC Diagnosis Reperfusion therapy ≤ 10 min Patient delay ………..……………….... ………..………………......... ………..………………... System delay ………..………………................. Time to reperfusion therapy Wire passage in culprit artery (primary PCI) Start of lysis Steg et al, EHJ 2012;33:2569-2619

Door to balloon in hospitals with and without cath labs in Kuwait Adan Hospital Cardiology response time Door to ECG ECG to Cardiology Door to balloon 7 9 4 64 Mubarak AlKabeer Hospital Door to ECG ECG to Cardiology Cardiology response time Door to balloon Ambulance notification Ambulance response Ambulance trip time 18 20 3 5 13 30 111

In-hospital cardiac catheterization

Prehospital and in-hospital management Reperfusion stratergies within 24 h of FMC STEMI diagnosis Primary- PCI capable center EMS or non primary-PCI capable center Preferably < 60 min PCI possible <120 min? Immediate transfer to PCI center Primary - PCI Yes No Preferably ≤ 90 min (≤ 60 min in early presenters) Preferably ≤ 30 min Rescue PCI Immediate transfer to PCI center Immediately No Successful fibrinolysis Immediate fibrinolysis Yes Preferably 3-24 h Coronary angiography Steg et al, EHJ 2012;33:2569-2619

PCI post lysis Recommendations Class Level Transfer to a PCI capable center following fibrinolysis Is indicated in all patient after fibrinolysis I A Interventions following fibrinolysis Rescue PCI is indicated immediately when fibrinolysis has failed (< 50% ST- segment resolution at 60 min). Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis. B Steg et al, EHJ 2012;33:2569-2619

Kuwait Gulf COAST population Rates of inhospital cath for STEMI patients STEMI (288) n (%) Cath during hospital stay 120 (42) Adan Hospital 61 (87) The rest of hospitals 59 (27) Hospital arrival to PCI at Adan, Mean±SD, Median (days) 0.86±1.2, 0.00 Hospital arrival to PCI excluding Adan, Mean±SD, Median (days) 4.4±3.5, 3

Management of hyperglycemia in the acute phase of STEMI Recommendations Class Level Measurement of glycaemia is indicated at initial evaluation in all patients, and should be repeated in patients with know diabetes or hyperglycemia I C Plans for optimal outpatient glucose control and secondary prevention must be determined in patients with diabetes before discharge The goals of glucose control in the acute phase should be to maintain glucose concentrations ≤11.0 mmol/L (200mg/dL) while avoiding fall of glycaemia<5 mmol/L (<90mg/dL). In some patients, this may require a dose-adjusted insulin infusion with monitoring of glucose, as long as hypoglycemia is avoided IIa B A measurement of fasting glucose and HbA1c and , in some cases, a post- discharge oral glucose tolerance test should be considered in patients with hyperglycemia but without a history of diabetes Routine glucose-insulin-potassium infusion is not indicated III A Remember, STEMI management is not just about reperfusion therapy Steg et al, EHJ 2012;33:2569-2619

Routine therapies in the acute, subacute and long term phase of STEMI Recommendations Class Level Oral treatment with betablockers should be considered during hospital stay and continued thereafter in all STEMI patients without contraindications IIa B Oral treatment with betablockers is indicated in patients with heart failure or LV dysfunction I A A fasting lipid profile must be obtained in all STEMI patients, as soon as possible after presentation C It is recommended to initiate or continue high dose statins early after admission in all STEMI patients without contraindication or history of intolerance, regardless of initial cholesterol values Reassessment of LDL should be considered after 4-6 weeks to ensure that a target value of ≤1.8 mmol/L (70 mg/dL) has been reached Steg et al, EHJ 2012;33:2569-2619

Routine therapies in the acute, subacute and long term phase of STEMI Recommendations Class Level ACE Inhibitors are indicated starting within the first 24 h of STEMI in patients with evidence of heart failure, LV systolic dysfunction, diabetes or an anterior infarct I A An ARB, preferably valsartan, is an alternative to ACE inhibitors in patient with heart failure or LV systolic dysfunction, particularly those who are intolerant to ACE inhibitors B ACE inhibitor should be considered in all patients in the absence of contraindications IIa Aldosterone antagonists are indicated in patients with an ejection fraction ≤40% and heart failure or diabetes, provided no renal failure or hyperkalaemia Steg et al, EHJ 2012;33:2569-2619

Adherence to medical therapy

Gulf COAST STEMI/NSTEMI 2012 Gulf RACE 2007¹ EHS-ACS-II 2004² NRMI-5 2004-2006³ Aspirin at arrival (%) 99 98 97 90 Aspirin prescribed at discharge (%) 91 Beta- blocker at discharge (%) 85 78 71 89 Statin at discharge (%) 84 80 82 Clopidogrel at discharge for medically treated AMI patients (%) 67 57 63 -

From plaque formation to progression to clinical manifestations STABLE No symptoms Silent ischemia Stable angina Slow Risk factor Atherosclerosis progression UNSTABLE Unstable angina NSTEMI STEMI Sudden cardiac death Accelerated Progression Atherothrombosis

Work up of ischemic chest pain Admission Working diagnosis Acute Coronary Syndrome Persistent ST-elevation ST/T– abnormalities normal or undetermined ECG ECG troponin rise/fall troponin normal Bio-chemistry Diagnosis STEMI NSTEMI Unstable Angina Hamm et al, EHJ 2011;32:2999-3054

Criteria for high risk with indication for invasive management Primary Relevant rise or fall in troponin Dynamic ST- or T- wave changes (symptomatic or silent) Secondary Diabetes mellitus Renal insufficiency (eGFR < 60 mL/min/1.73m2) Reduced LV function (ejection fraction < 40 %) Early post infarction angina Recent PCI Prior CABG Intermediate to high GRACE risk score Hamm et al, EHJ 2011;32:2999-3054

Gulf COAST Kuwait population NSTEMI (574) n (%) Age (Mean ±SD) 61.7±12.3 Female 221 (39) Hypertension 403 (70) Diabetes 391 (68) Smoking 177 (31) Prior MI 208 (36) Prior PCI 120 (21) Prior CABG 45 (8) Prior TIA 28 (5) Prior stroke 57 (10)

Decision – making algorithm in ACS 1.Clinical Evaluation 2. Diagnosis/Risk Assessment 3. Coronary angiography STEMI reperfusion urgent < 120 min Evaluation Quality of chest pain. Symptom - orientated physical examination. Short history for the likelihood of CAD. Electrocardiogram (ST elevation?) Validation Response to antianginal treatment. Biochemistry/troponin. ECG Echocardiogram. Calculated risk score (GRACE) Risk Criteria. Optional: CT, MRI, scintigraphy. ACS possible early <24h <72h No CAD no/elective Hamm et al, EHJ 2011;32:2999-3054

Antithrombotic treatment in NSTE ACS Targets for antithrombics Antiplatelet Anticoagulation Tissue Factor Collagen Aspirin Plasma clotting cascade Fondaparinux ADP Clopidogrel Prasugrel Ticagrelor Thromboxane A2 Prothrombin LMWH Heparin AT Factor Xa Conformational activation of GPIIb/IIIa AT GPIIb/IIIa inhibitors Thrombin Platelet aggregation Bivalirudin Fibrinogen Fibrin Thrombus Hamm et al, EHJ 2011;32:2999-3054

Conclusions Management of ACS has evolved rapidly over the past few years. Early risk stratification and cardiac catheterization is a cornerstone in ACS management. If we want to benefit our patients, it is important that we examine what we do. Our ACS patients receive good medical therapy at discharge from hospital. However, we rely heavily on lytic therapy for reperfusion in STEMI and it is not administered in efficient timing to get the most benefit from it. In both STEMI and NSTE ACS, our use of cardiac catheterization falls short of guidelines recommendations.