Coronary Artery Disease UHCW Cardiology Teaching Dr Chris McAloon

Case One 65 year old man Playing golf Sudden onset chest pain Crushing, central, severe Vomiting No previous chest pain HTN, Ex-Smoker Otherwise well GTN helped – not resolved

History – what information do you need to elicit? Pain Character / Radiation / GTN spray effect Was this pain like your previous Angina/ MI pain? Autonomic features Risk factors Smoker / Hypertension / Diabetes Hyperlipidaemia / Family history Previous MI / CABG / PCI / CVA Differentials What makes cardiac chest pain? What does PCI and CANG stand for? What differentials do you have for chest pain? What differentials do they get?

Cardiac Sounding Chest Pain Central Crushing Chest Pain Exertional chest pain Occurs at rest Radiation Neck, arms (classically left) Levine’s Sign Clenched fist over chest Breathless Autonomic features

Isn’t Chest Pain always ACS? ECS ACS NTE Guidelines 2011

Examination Nicotine Stains GTN spray Xanthelasma Scar’s Evidence DM Chest Legs Evidence DM BP/ Pulse/ Failure

Examination 65 year old 35 year old Valve/ Congenital surgery CABG Ankles/shins for SVG scar Radial for graft scar CABG 35 year old Metallic Click Look left lateral Cyanosis etc Valve/ Congenital surgery

Acute Coronary Syndrome ECS ACS Guidelines 2011

ESC Definition ACS Pain ECS ACS Guidelines 2011

Pathophysiology ACS Spectrum of acute coronary syndromes according to electrocardiographic and biochemical markers of myocardial necrosis (troponin T, troponin I, and creatine kinase MB), in patients presenting with acute cardiac chest pain Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

Plaque and Thrombin Formation Ischaemic Heart Disease Diagram of an unstable plaque with superimposed luminal thrombus Unstable angina and non-ST segment elevation myocardial infarction are generally associated with white, platelet-rich, and only partially occlusive thrombus. Microthrombi can detach and embolise downstream, causing myocardial ischaemia and infarction. In contrast, ST segment elevation (or Q wave) myocardial infarction has red, fibrin-rich, and more stable occlusive thrombus. Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

Ruptured Atheromatous Plaque and Occlusive Thrombus STEMI Histological appearance of a ruptured atheromatous plaque (bottom arrow) and occlusive thrombus (top arrow) resulting in acute myocardial infarction Occlusion epicardial artery Grech E D , Ramsdale D R BMJ 2003;326:1379-1381 ©2003 by British Medical Journal Publishing Group

ECG: ST elevation ECG Changes Site of Infarction Vessel Occluded V1-V3 Anteroseptal LAD V4, V5, AVL, I Anterior Lateral LAD, diagonal Widespread 1, AVL, V1-V6 Large Anterior Prox LAD (could be LMS - Pump probs II, III, AVF Inferior RCA (or Cx) - Bradyarrhythmia ↓ ST V1-V2 ↑ ST in post leads Posterior NB remember Cx occlusion can be silent on the ECG

ANTERIOR STEMI ST elevation V1-V6, reciprocal changes in II, III, AVF

Infero-posterior STEMI ST elevation in II, III and AF, R wave and ST depression in V1-2

Size of the Problem: England and Wales 2009-10 STEMI 31,412 in 2009-10 Frequency falling NSTEMI Estimated 100, 000 in 2009-10 Recorded frequency rising 50% not managed on ACU/ CCU BCS Recommendations Acute Coronary Care Oct 2011

30 Day Mortality Mortality rate of STEMI and NSTEMI simliar at 30 days BCS Recommendations Acute Coronary Care Oct 2011

STEMI Initial Diagnosis Regional wall abnormalities occur within seconds coronary arter occlusion ECS ACS STE Guidelines 2011

300mg Aspirin/ 600mg Clopidogrel Reperfusion: PCI / Fibrinolysis Management of STEMI THINK REPERFUSION STRATEGY: ■ Primary PCI if available (CALL THE CATH LAB) ■ Thrombolysis if not, then refer to PCI centre (GTN) ↓ High Flow Oxygen (15L) 300mg Aspirin/ 600mg Clopidogrel Analgesia: Morphine + Metoclopramide Reperfusion: PCI / Fibrinolysis

STEMI Management Successful Thrombolysis ST segment resolution 50% at 90 minutes ECS Revasculration Guidelines 2011

Standards STEMI Management Direct paramedic transfer to PPCI centre or timely inter-hospital transfer PPCI with first medical contact-to-balloon time <120 minutes Monitoring on CCU (including for repatriated patients) Early initiation of secondary prevention and cardiac rehabilitation ECS Revasculration Guidelines 2011

The Changing Face STEMI Mx BCS Recommendations Acute Coronary Care Oct 2011

The Changing Face STEMI Mx 95% England covered by PPCI networks Thrombolysis remains in place in remote centres Geography impacts time to PPCI centre 30% Thrombolysis fail to reperfuse and need immediate rescue PCI

ECS ACS STE Guidelines 2011

What is Percutaneous Coronary Intervention (PCI)? Disruption of occlusion using a balloon Stent deployed to maintain anterograde blood flow Types Primary PCI – PCI within 2 hours Rescue PCI – PCI after failed thrombolysis Facilitated PCI – PCI bridged with lytic therapy Time delayed PPCI

Distal Embolisation of a Platelet-Rich Thrombus causing Occlusion of Intramyocardial Arteriole NSTEMI Distal embolisation of a platelet-rich thrombus causing occlusion of intramyocardial arteriole (arrow). Such an event may result in micro-infarction and elevation of markers of myocardial necrosis Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

Case Two 48 year old lady Shopping Central dull Pain on walking Not relieved GTN spray Gets on exertion normally Recently distant decreasing to onset pain Pain last night in bed

Worrying ECG? Electrocardiogram of a 48 year old woman with unstable angina (top). Note the acute ischaemic changes in leads V1 to V5 (arrows). Coronary angiography revealed a severe mid-left anterior descending coronary artery stenosis (arrow, bottom left), which was successfully stented (bottom right)‏ Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

What do you do as the SHO clerking patient in A+E?

Defining Angina Pectoris Stable Angina pattern of frequency, intensity, ease of provocation, or duration does not change over several weeks Accelerating Angina  change in the pattern of stable angina greater ease of provocation, more prolonged episodes, and episodes of greater severity or more frequent use of sublingual GTN Unstable Angina  pattern of chest pain changes abruptly

Three Presentations UA Angina at rest—Also prolonged, usually > 20 minutes Angina of new onset—At least CCS class III in severity Angina increasing—Previously diagnosed angina that has become more frequent, longer in duration, or lower in threshold (change in severity by > 1 CCS class to at least CCS class III)

Angina Pectoris CCS Classification Class I – Pain strenuous exertion Class II – Slight limitation ordinary exertion Class III – Marked limitation physical exertion Class IV – Pain on any exertion CCS = Canadian Cardiology Society The anaerobic threshold is crossed and the patient develops symptomatic angina pectoris.  Supply and demand

TIMI Risk Score ≥3 risk factors for coronary artery disease ≥50% coronary stenosis on angiography ST segment change >0.5 mm ≥2 anginal episodes in 24 hours before presentation Elevated serum concentration of cardiac markers Use of aspirin in 7 days before presentation

High TIMI score and Mortality Rates of death from all causes and non-fatal myocardial infarction at 14 days, by TIMI risk score. Note sharp rate increase when score ≥ 3 Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

Bleeding Risk Crusade bleeding score ECS ACS Guidelines 2011

NSTEMI Outcome Based Location BCS Recommendations Acute Coronary Care Oct 2011

Simplified management pathway for patients with unstable angina or non-ST segment elevation myocardial infarction. Simplified management pathway for patients with unstable angina or non-ST segment elevation myocardial infarction Grech E D , Ramsdale D R BMJ 2003;326:1259-1261 ©2003 by British Medical Journal Publishing Group

Acute Management of NSTEMI-ACS Aspirin 300mg Clopidogrel 300mg (600mg if going to the lab) LMWH Bisoprolol / Atorvastatin 80mg ON/ ACE/ARB (can be next day) GTN Spray/ Infusion HIGH RISK patients: GPIIbIIIa Cath Lab within 48-96hrs

Timing Early Invasive Strategy High risk (GRACE >140) within 24 hours At Stafford discuss with Stoke Intermediate risk (GRACE < 140) and high risk criterion within 72 hours Low risk with recurrent symptoms Stress Test

Anti-thrombotic Therapy ECS ACS Guidelines 2011

Prasugrel Thienopyridine related to Clopidogrel Active metabolite irreversible inhibitor of ADP receptor Effective when Clopidogrel Resistance More rapid/ greater/ more consistent platelet inhibition No drug interactions Licensed used STEMI going PPCI

Prasugrel vs Clopidogrel Figure 1. Cumulative Kaplan-Meier Estimates of the Rates of Key Study End Points during the Follow-up Period. Panel A shows data for the primary efficacy end point (death from cardiovascular causes, nonfatal myocardial infarction [MI], or nonfatal stroke) (top) and for the key safety end point (Thrombolysis in Myocardial Infarction [TIMI] major bleeding not related to coronary-artery bypass grafting) (bottom) during the full follow-up period. The hazard ratio for prasugrel, as compared with clopidogrel, for the primary efficacy end point at 30 days was 0.77 (95% confidence interval [CI], 0.67 to 0.88; P<0.001) and at 90 days was 0.80 (95% CI, 0.71 to 0.90; P<0.001). Data for the primary efficacy end point are also shown from the time of randomization to day 3 (Panel B) and from 3 days to 15 months, with all end points occurring before day 3 censored (Panel C). In Panel C, the number at risk includes all patients who were alive (regardless of whether a nonfatal event had occurred during the first 3 days after randomization) and had not withdrawn consent for follow-up. The P values in Panel A for the primary efficacy end point were calculated with the use of the Gehan-Wilcoxon test; all other P values were calculated with the use of the log-rank test. Wiviott SD et al. N Engl J Med 2007;357:2001-2015

Prasugrel vs Clopidogrel Figure 2. Hazard Ratios and Rates of the Primary End Point, According to Selected Subgroups of Study Patients. The primary end point was defined as death from cardiovascular causes, nonfatal myocardial infarction (MI), or nonfatal stroke. The percentages are Kaplan-Meier estimates of the rate of the end point at 15 months. For each subgroup, the size of the square is proportional to the number of patients in the subgroups and represents the point estimate of the treatment effect. The overall treatment effect of prasugrel as compared with clopidogrel is represented by the diamond, and the dashed vertical line represents the corresponding overall point estimate. None of the P values for interactions were significant. Glycoprotein IIb/IIIa-receptor antagonist use was that during the index hospitalization. Wiviott SD et al. N Engl J Med 2007;357:2001-2015

Ticagrelor Cyclopentyl-triazolo-pyrimidine Reversible inhibitor of ADP receptor Rapid/ Predictable action CYP450 interaction NICE approval October 2011 ACS

Ticagrelor vs Clopidogrel Figure 1. Cumulative Kaplan-Meier Estimates of the Time to the First Adjudicated Occurrence of the Primary Efficacy End Point. The primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - occurred significantly less often in the ticagrelor group than in the clopidogrel group (9.8% vs. 11.7% at 12 months; hazard ratio, 0.84; 95% confidence interval, 0.77 to 0.92; P<0.001). Wallentin L et al. N Engl J Med 2009;361:1045-1057

Ticagrelor vs Clopidogrel Figure 2. Cumulative Kaplan-Meier Estimates of the Time to the First Major Bleeding End Point, According to the Study Criteria. The time was estimated from the first dose of the study drug in the safety population. The hazard ratio for major bleeding, defined according to the study criteria, for the ticagrelor group as compared with the clopidogrel group was 1.04 (95% confidence interval, 0.95 to 1.13). Wallentin L et al. N Engl J Med 2009;361:1045-1057

Prescribing in CKD ECS ACS Guidelines 2011

Secondary Prevention for IHD Immediately Aspirin ± PPI (Bleeding risk) Clopidogrel (12 months) B Blocker ACEi- if intolerant give ARB Atorvastatin 80mg GTN Spray PRN 15 minute rule Lifestyle Diet Physical Activity Stop Smoking Cardiac Rehab Sex and stairs rule

Summary Definitions ACS Incidence and Prevalence Pathophysiology Differential Diagnoses STEMI Intervention – current evidence NSTEMI intervention – current evidence Antithrombotic therapy use New anti-thrombotics