Updates in Acute Coronary Syndromes Management

Mohammad Zubaid, MB, ChB, FRCPC, FACCProfessor of Medicine, Kuwait University

Head, Division of CardiologyMubarak Alkabeer Hospital

Kuwait

The 1st Kuwait-North American update in Internal Medicine4th Medical Scientific Conference – Mubarak Alkabeer Hospital

February 7, 2014 – Jumeirah hotel, Kuwait

From plaque formation to progression to clinical manifestations

Plaque formation Clinical manifestations

STABLENo symptomsSilent ischemiaStable angina

UNSTABLEUnstable anginaNSTEMISTEMISudden cardiac death

Risk factor Slow

Atherosclerosisprogression

Atherothrombosis

Accelerated Progression

Distribution of ACS type in Kuwait

Discharge diagnosis 2534 patients

STEMI (288)n (%)

Age (Mean ±SD) 56.7±13.3Female 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 7 (2)Prior stroke 19 (7)

Gulf COAST 2012

Kuwait population

Pooled analysis of the short-term results from 23 randomized trials comparing primary PCI and fibrinolytic therapy in 7739 patients

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.

I B

Steg et al, EHJ 2012;33:2569-2619

Periprocedural antithrombotic medicationsin 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:

I A

• Prasugrel in clopidogrel-naive patients, if no history of prior stroke/TIA, age <75 years.

I B

• Ticagrelor I B

• Clopidogrel, preferably when prasugrel or ticagrelor are either not available or contraindicated

I C

Steg et al, EHJ 2012;33:2569-2619

Fibrinolytic therapy

Recommendations Class Level

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 IIa A

A fibrin – specific agent (tenecteplase, alteplase, reteplase) is recommended ( over non – fibrin specific agents)

I B

Oral or i.v. aspirin must be administered I B

Clopidogrel is indicated in addition to aspirin I A

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).

I A

Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis.

I 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

Primary - PCI

Rescue PCI

Coronary angiography

Immediate fibrinolysis

PCI possible <120 min?

Successful fibrinolysis

Yes No

Yes

No

Immediate transfer to PCI center

Immediate transfer to PCI center

Preferably < 60 min

Preferably ≤ 90 min(≤ 60 min in early presenters)

Preferably 3-24 h

Immediately

Preferably ≤ 30 min

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

Steg et al, EHJ 2012;33:2569-2619

Components of delay in STEMI

Symptom onset FMC

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Reperfusion therapyDiagnosis

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≤ 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

Kuwait

(n=259)

Oman

(n= 315)

UAE

(n= 129)

Bahrain

(n= 119)

PPCI (%) 60.3 40 29

Lysis (%)86

9249 58

Shortfall (%)8

7.711 13

Reperfusion in eligible patients

Kuwait

Adan Hospital

(n=56)

Rest of Hospital

(n= 203)

PPCI (%) 270

Lysis (%)64

93

Shortfall (%)9

7

Was reperfusion administered in time?

Reperfusion Timeline

Thrombolysis in Kuwait

Thrombolysis Adan Hospital

(n=37)

Rest of Hospital

(n= 188)

Median D2NT (min) 34 41

D2NT ≤30 min (%) 43 36

Primary PCI experienceAdan Hospital

November 13 – December 30, 2013

Distribution of timeline

During working hours14 patients

After working hours45 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%

Distribution of timeline during and after normal working hours

Primary PCI experienceAdan Hospital

November 13 – December 30, 2013

Primary PCI experienceMubarak Alkabeer Hospital

November 13 – December 30, 2013Held off for two weeks in the middle

Distribution of timeline

Primary PCI experienceMKH vs. Adan Hospital

November 13 – December 30, 2013

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% 0

Door to balloon ≤90 minutes 85% 15%

Door to balloon ≤120 minutes 97% 65%

Distribution of timeline (values in mean)

Components of delay in STEMI

Symptom onset FMC

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Reperfusion therapyDiagnosis

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≤ 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

Cardiology response timeDoor to ECG

ECG to Cardiology

Door to balloon

Door to ECGECG to

CardiologyCardiology

response time Door to balloon

Ambulance notification

Ambulance response

Ambulance trip time

Adan Hospital

Mubarak AlKabeer Hospital

97 4 64

18 3 5 13 30 11120

Door to balloon in hospitals with and without cath labs in Kuwait

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

Primary - PCI

Rescue PCI

Coronary angiography

Immediate fibrinolysis

PCI possible <120 min?

Successful fibrinolysis

Yes No

Yes

No

Immediate transfer to PCI center

Immediate transfer to PCI center

Preferably < 60 min

Preferably ≤ 90 min(≤ 60 min in early presenters)

Preferably 3-24 h

Immediately

Preferably ≤ 30 min

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).

I A

Emergency PCI is indicated in the case of recurrent ischemia or evidence of reocclusion after initial successful fibrinolysis.

I 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 I C

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

IIa B

Routine glucose-insulin-potassium infusion is not indicated III A

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 I 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

I A

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

IIa C

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

I B

ACE inhibitor should be considered in all patients in the absence of contraindications IIa A

Aldosterone antagonists are indicated in patients with an ejection fraction ≤40% and heart failure or diabetes, provided no renal failure or hyperkalaemia

I B

Steg et al, EHJ 2012;33:2569-2619

Adherence to medical therapy

Gulf COAST

STEMI/NSTEMI

Gulf COAST 2012

Gulf RACE2007¹

EHS-ACS-II2004²

NRMI-52004-2006³

Aspirin at arrival (%) 99 98 97 90

Aspirin prescribed at discharge (%) 97 97 90 91

Beta- blocker at discharge (%) 85 78 71 89

Statin at discharge (%)

97 84 80 82

Clopidogrel at discharge for medically treated AMI patients (%)

67 57 63 -

From plaque formation to progression to clinical manifestations

Plaque formation Clinical manifestations

STABLENo symptomsSilent ischemiaStable angina

UNSTABLEUnstable anginaNSTEMISTEMISudden cardiac death

Risk factor Slow

Atherosclerosisprogression

Atherothrombosis

Accelerated Progression

Work up of ischemic chest pain

Admission

Working diagnosis

Bio-chemistry

Acute Coronary Syndrome

ECGPersistent

ST-elevation

Diagnosis NSTEMI Unstable Angina

troponin rise/fall

ST/T– abnormalities

normal or undetermined

ECG

troponin normal

STEMI

Chest Pain

Hamm et al, EHJ 2011;32:2999-3054

Criteria for high risk with indicationfor 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

NSTEMI (574)n (%)

Age (Mean ±SD) 61.7±12.3Female 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)

Gulf COAST

Kuwait population

Decision – making algorithm in ACS

1.Clinical Evaluation 2. Diagnosis/Risk Assessment 3. Coronary angiography

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.

STEMI

No CAD

ACS possible

reperfusion

urgent < 120 min

no/elective

early <24h

<72h

Hamm et al, EHJ 2011;32:2999-3054

Antithrombotic treatment in NSTE ACS

Anticoagulation

Fondaparinux

Bivalirudin

LMWH Heparin

Aspirin

GPIIb/IIIainhibitors

Antiplatelet

Clopidogrel PrasugrelTicagrelor

Tissue Factor

Plasma clotting cascade

Prothrombin

Thrombin

Fibrinogen Fibrin

Collagen

ADP

Thromboxane A2

Conformational activation of GPIIb/IIIa

Platelet aggregation

Thrombus

Factor Xa

AT

AT

Targets for antithrombics

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.