Management of Acute Coronary Syndrome

Dr Simon Corbett

Consultant Interventional Cardiologist University Hospital Southampton NHS Foundation Trust

RCP Advanced Medicine 2020 Specialty Breakout Session – Cardiology 10th February 2020 Conflicts of Interest

• None

• (although I am Topic Advisor on new NICE clinical guideline on ACS which will be released for consultation this Friday) Outline

• Case-based review of contemporary management of non-ST-elevation ACS • I’m not covering STEMI • Diagnostic dilemmas – do high sensitivity troponin assays help or hinder patient care? • Which medical therapies should I be using? • Is there a role for risk assessment? Case 1

• 56 year old man • No regular medications • Ex-smoker (25 pack year history) • Woken up with central constricting chest discomfort at 0330 • Slightly sweaty and nauseated so calls 999 after 30 minutes • Given aspirin and GTN by paramedics • Pain free on admission to hospital • HR 78bpm, BP 134/82 • High sensitivity Troponin I level on admission 187 ng/l (99th centile 34.2) POLL Question 1 OPEN What is the most likely diagnosis?

1 ST-elevation MI? 0% 2 Pulmonary embolism? 0% 3 Unstable angina? 0% 4 Non-ST-elevation MI? 0% 5 I’m not sure, I need more information? 0% Question 1

• What is the most likely diagnosis?

1. ST-elevation MI? 2. Pulmonary embolism? 3. Unstable angina? 4. Non-ST-elevation MI? 5. I’m not sure, I need more information? Question 2 POLL What more information do you think youOPEN need? 1. Echocardiogram? 0% 2. Coronary angiogram? 0% 3. Repeat hsTn after 1 hour? 0% 4. Repeat hsTn after 3 hours? 0% 5. Repeat hsTn after 10 hours? 0% Question 2

• What more information do you think you need?

1. Echocardiogram? 2. Coronary angiogram? 3. Repeat hsTn after 1 hour? 4. Repeat hsTn after 3 hours? 5. Repeat hsTn after 10 hours? Case 2

• 56 year old man • No regular medications • Ex-smoker (25 pack year history) • Woken up with central constricting chest discomfort at 0330 • Slightly sweaty and nauseated so calls 999 after 30 minutes • Given aspirin and GTN by paramedics • Pain free on admission to hospital • HR 78bpm, BP 134/82 • High sensitivity Troponin I level on admission 30 ng/l (99th centile 34.2) POLL Question 3 OPEN What is the most likely diagnosis?

1. ST-elevation MI? 0% 2. Pulmonary embolism? 0% 3. Unstable angina? 0% 4. Non-ST-elevation MI? 0% 5. I’m not sure, I need more information? 0% Question 3

• What is the most likely diagnosis?

1. ST-elevation MI? 2. Pulmonary embolism? 3. Unstable angina? 4. Non-ST-elevation MI? 5. I’m not sure, I need more information? POLL Question 4 OPEN What more information do you need?

1. Echocardiogram? 0% 2. Coronary angiogram? 0% 3. Repeat hsTn after 1 hour? 0% 4. Repeat hsTn after 3 hours? 0% 5. Repeat hsTn after 10 hours? 0% Question 4

• What more information do you need?

1. Echocardiogram? 2. Coronary angiogram? 3. Repeat hsTn after 1 hour? 4. Repeat hsTn after 3 hours? 5. Repeat hsTn after 10 hours? Question 4

• What more information do you need?

1. Echocardiogram? 2. Coronary angiogram? 3. Repeat hsTn after 1 hour? 4. Repeat hsTn after 3 hours? 5. Repeat hsTn after 10 hours? TRYING TO MAKE SENSE OF HIGH SENSITIVITY TROPONINS Know your Troponin Assay

• There is no such thing as a ‘normal’/ ‘upper limit of normal’ troponin level • Rather, MYOCARDIAL INJURY is defined as finding at least one troponin level above the 99th centile of troponin levels found in a normal population • There is a broad range of cardiac and non-cardiac conditions that can cause myocardial injury • Hs Troponin cannot be taken in isolation and must be placed in context of CLINICAL PRESENTATION and DYNAMIC CHANGES IN TROPONIN LEVELS (as per Universal Definition of MI) Know your Troponin Assay

• The evolution and introduction of ever-more sensitive troponin assays invalidates the (always flawed) concept of POSITIVE and NEGATIVE troponin measurements. • Troponin is a quantitative, continuous variable – the higher the level, the greater the myocardial injury AND the higher the likelihood of MI • The latest generation of troponin assays are highly sensitive - will detect troponin in blood of 50-90% of healthy individuals • Will detect acute troponin elevations much earlier than the 10-12 hrs after ischaemia onset of original troponin assays Know your Troponin Assay • Some of the latest hsTn assays are so sensitive and accurate that they can detect meaningful rises in troponin levels at 1 hour below the 99th centile reference limit • There will be a drop in unstable angina and rise in NSTEMI diagnoses (type 1 and type 2) • You must know/your lab must tell you what these levels are for the troponin assay in your hospital • False positives are always possible Know your Troponin Assay

ng/L

10,000

1,000

100

50 14 10 5

Mueller C. Biomarkers and acute coronary syndromes: an update. Eur Heart J (2014);35:p552 ACS – Type 1 MI

Type 2 MI (not ACS)

Know your Troponin Assay

ng/L

10,000

1,000

100

50 14 10 Hs troponin is5 diagnostically useless if result is within 1 order of magnitude of 99th centile

Mueller C. Biomarkers and acute coronary syndromes: an update. Eur Heart J (2014);35:p552 hsTn Summary

ESC 2015 non-ST- elevation ACS guidelines ESC 0 and 3 hour algorithm ESC 0 and 1 hour algorithm Case 1

1. Aspirin 300mg stat, fondaparinux 2.5mg od, calculate 6 month mortality risk using GRACE score? 0% 2. Aspirin 300mg stat, ticagrelor 180mg stat, fondaparinux 2.5mg od, refer for coronary angiography within 72 hours? 0% 3. Aspirin 300mg stat, calculate 6 month mortality risk using GRACE score, prasugrel 60mg stat if GRACE score >140? 0% 4. Aspirin 300mg stat, fondaparinux 2.5mg od, Clopidogrel 600mg and refer for coronary angiography within 96 hours? 0% 5. Aspirin 300mg stat, enoxaparin 1mg/kg bd, refer for coronary angiography within 24 hours and load with prasugrel 60mg stat if proceeding to PCI? 0% Question 5

• According to NICE CG94 (Unstable Angina and NSTEMI), what should the next management steps be?

1. Aspirin 300mg stat, fondaparinux 2.5mg od, calculate 6 month mortality risk using GRACE score? 2. Aspirin 300mg stat, ticagrelor 180mg stat, fondaparinux 2.5mg od, refer for coronary angiography within 72 hours? 3. Aspirin 300mg stat, calculate 6 month mortality risk using GRACE score, prasugrel 60mg stat if GRACE score >140? 4. Aspirin 300mg stat, fondaparinux 2.5mg od, Clopidogrel 600mg and refer for coronary angiography within 96 hours? 5. Aspirin 300mg stat, enoxaparin 1mg/kg bd, refer for coronary angiography within 24 hours and load with prasugrel 60mg stat if proceeding to PCI? POLL Question 6 According to European Society of Cardiology Guidelines on non-STOPEN- elevation ACS, what should the next management steps be?

• According to European Society of Cardiology Guidelines on non-ST-elevation ACS, what should the next management steps be?

WHAT ARE THE DIFFERENCES BETWEEN NICE AND ESC? ROLE OF RISK STRATIFICATION NICE CG94 ESC uses GRACE and hsTroponin GRACE (Global Registry of Acute Coronary Events)

• GRACE score has best discriminatory and predictive power of current tools

• Retrospective analysis of ONS-tracked 6 month mortality after NSTEACS in UK shows strong correlation with GRACE (NICE CG94)

Case 1

NICE Recommendation

ESC uses GRACE and hsTroponin Why Stents in NSTE-ACS?

30-DAY DATA ARE REVERSED – MORE DEATH OR MI IN INVASIVE ARM DO NOT FORGET THERE IS A MORBIDITY AND MORTALITY ASSOCIATED WITH INVASIVE CORONARY ANGIOGRAPHY! NICE Recommendation

OFFER INVASIVE APPROACH

Compare to ESC - no troponin elevation, GRACE score >140 = 6 month mortality 16%! BUT is borderline elevation hsTn good enough risk stratification? WHICH ANTI-PLATELET DRUGS? ESC NICE

• CG94 (2010) only refers to clopidogrel • TA317 (2014, replaced TA182 (2009)) – “Prasugrel in combination with aspirin is recommended as an option in adults…with ACS…having percutaneous coronary intervention” • TA236 (2011) – “Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months as a treatment option in adults with ACS…”

Cumulative Kaplan-Meier Estimates of the Rates of Key Study End Points during the Follow-up Period

Wiviott SD et al. N Engl J Med 2007;357:2001-2015 Ticagrelor Clopidogrel

DAPT Summary •NICE and ESC agree on Aspirin for Everyone •Clopidogrel, Prasugrel and Ticagrelor theoretically recommended as options by both NICE and ESC •RCT data suggest Prasugrel and Ticagrelor both better than Clopidogrel (but probably more bleeding) •Prasugrel only for patients treated with PCI •Ticagrelor suitable for all ACS and appears to have lower mortality than clopidogrel •UK audit data (2017-18) show 58% clopidogrel, 40% ticagrelor, 2% prasugrel (in PCI treated patients) •Wouldn’t it be nice to compare Prasugrel and Ticagrelor…?

SUMMARY

• Reviewed Guideline recommended diagnosis and treatment of NSTEACS • Highlighted the Utility and Pitfalls of high sensitivity Troponin measurement • Shown you how risk stratification can (and should) guide management • Reviewed options for DAPT • Encourage you to keep an eye out for forthcoming updated NICE and ESC Guidelines • Will ISAR REACT 5 change practice??? Questions?