CHEST PAIN AND SUSPECTED ACUTE CORONARY SYNDROME GUIDELINES

Transcription

1 CHEST PAIN AND SUSPECTED ACUTE CORONARY SYNDROME GUIDELINES Policy authors Accountable Executive Lead Approving body Policy reference Dr. Vinoda Sharma; Dr. Chetan Varma Consultant Cardiologists Medical Director/ Clinical Directors Clinical Effectiveness Committee Drugs and Therapeutics Committee SWBH/Cardio/03 Overall purpose of the guideline Update the SWBH Trust protocol on chest pain and suspected acute coronary syndrome Principal target audience Medical and nursing staff Application All patients presenting with chest pain and suspected acute coronary syndrome to SWBH Trust Scope Triage and management of patients based on history and high sensitivity troponin T National Guidance incorporated 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation Version No Date Approved DOCUMENT CONTROL AND HISTORY Date of implementation Next Review Date Reason for change (e.g. full rewrite, amendment to reflect new legislation, updated flowchart, etc.) 1 October 2009 October 2009 October 2011 New Guidelines 2 March 2013 March 2013 May September 2016 September 2016 September 2019 Full review Acute Coronary Syndrome Guidelines 1 of 18

2 PREAMBLE This major revision of the chest pain and acute coronary syndrome protocol was developed after the new European Society of Guidelines in September From Summer 2015 all interventional cardiac services have been reconfigured to Birmingham City Hospital. There will continue to be on-going cardiology support for Sandwell in the form of daily cardiology consultant and registrar ward rounds. All patients requiring cardiac intervention presenting to Sandwell are transferred to the cardiac wards in City Hospital. The urgency of transfer will be dictated by clinical need. Patients with ST Elevation Myocardial Infarction will also be admitted whenever possible directly to City Hospital. Initial management of patients with suspected ACS in ED and AMU will continue to be identical across both sites. This revised protocol reflects the latest NICE (2014) and European Society Guidelines (2015), emerging evidence on the use of cardiac biomarkers and antithrombotic therapy, and the need for efficient patient flow. Dr Vinoda Sharma Consultant Cardiologist Dr Chetan Varma Consultant Cardiologist Acute Coronary Syndrome Guidelines 2 of 18

3 Chest Pain and Suspected Acute Coronary Syndrome Guidelines Contents Page Chest Pain Pathway Table 1 Troponin algorithm Introduction ACS Subgroups Protocol scope Traffic light system 6 2 Management in Emergency Department lead ECG STEMI High Risk ECG features Repeat 12-lead ECG Clinical assessment Blood tests Troponin Diagnosing NSTEACS Time of onset of chest pain and troponin Initial Management of Patients with ACS in Emergency Department 8 3 Management in Acute Medical Unit (AMU) Cardiology ward rounds lead ECG High risk ECG changes NSTEMI Risk stratification in NSTEACS (GRACE) Management of NSTEACS pending transfer to cardiology ward 3.7 Fondaparinux 3.8 Patients on anticoagulants 3.9 Other medications 3.10 Risk criteria mandated invasive management 4 Management in cardiology ward (D5/D7) Review Diagnosis Medication IV Beta-Blockers GRACE Score Tirofiban Special Groups (Elderly, Diabetes, Renal Failure, Atrial Fibrillation) 13 5 References 15 Appendix I Glycoprotein IIb/IIIa Inhibitors 16 Appendix II Cangrelor (IV antiplatelet) 17 Appendix III Antiplatelet Agents Acute Coronary Syndrome Guidelines 3 of 18

4 Chest Pain Pathway Algorithm Acute Coronary Syndrome Guidelines 4 of 18

5 Table 1: Acute Cardiac Chest Pain Troponin Algorithm Table Troponin Patient Low Risk Intermediate Risk High Risk Low <5ng/L Hotslot clinic (if indicated) Hotslot clinic Hotslot Clinic Repeat Troponin in 3 hours Intermediate 5-51 ng/l If troponin <5 Hotslot clinic Refer Cardiology Refer Cardiology If troponin 5 refercardiology High 52ng/L Refer Cardiology Refer Cardiology Refer Cardiology Acute Coronary Syndrome Guidelines 5 of 18

6 These notes accompany the flow chart on page 4 1. INTRODUCTION 1.1 Acute coronary syndrome (ACS) covers: i. ST elevation myocardial infarction (STEMI) ii. iii. Non ST elevation myocardial infarction (NSTEMI) Unstable angina (UA) 1.2 These guidelines primarily cover the management of patients with suspected ACS without ST-segment elevation (NSTEMI/UA, also referred to as NSTEACS). 1.3 The algorithm has been devised using a traffic light system as follows: RED: Immediate specialist cardiology management is required (STEMI or NSTEMI with high risk ECG features). AMBER: Urgent cardiology review within 24 hours is required (NSTEMI or High risk NSTEACS). GREEN: Non-urgent cardiology review is appropriate - e.g. outpatient HOT SLOT clinic. 2 MANAGEMENT IN EMERGENCY DEPARTMENT 2.1 All individuals with chest pain must have a 12 lead ECG taken within 5 minutes of presenting to the department. This ECG should be reviewed and reported by a practitioner competent in ECG interpretation within 5 minutes of being taken. 2.2 In the presence of clear ST elevation or variable/new LBBB where the diagnosis is likely STEMI, then the primary percutaneous coronary intervention (PCI) team must be activated without delay (Ext 2222). Patients with STEMI require urgent revascularisation with primary PCI as prognosis worsens with each passing minute before this is achieved. If in doubt then more senior interpretation of the ECG must be sought immediately. After reconfiguration self-presenting patients to the Non-PCI centre Emergency Department (Sandwell) with STEMI must be transferred immediately by 999 ambulance as a life threatening emergency to arrive at City Hospital within 30 minutes. Possible STEMI pts should be assessed in ED by the on call cardiology SpR within 10 minutes of call out. Non-resident cardiac catheter lab staff are expected to be in the cath lab as soon as possible within 30 mins. This may be reduced in time dependent upon outcome audit data. Acute Coronary Syndrome Guidelines 6 of 18

7 2.3 If cardiac sounding chest pain with high-risk ECG abnormalities as defined below are present then immediate cardiology consultation should be sought by contacting the cardiology registrar: i. new ST depression greater than 1mm in more than 1 lead, ii. new biphasic T wave in V1 to V3 iii. new T wave inversion or iv. ventricular arrhythmia. Patients with on-going symptoms and/or high risk-ecg features above should be directly admitted to the cardiac ward from ED following discussion with the cardiology registrar. After reconfiguration patients presenting to Sandwell ED with high-risk features above should be discussed with medical on call registrar to consider urgent transfer to City Hospital CCU for further assessment by the resident cardiology registrar. 2.4 A second repeat ECG should be performed within 15 minutes of first ECG to document whether changes are dynamic. If unsure seek senior advice. 2.5 Clinical assessment - A structured history and physical examination should be performed. If pain clearly non-cardiac then alternative diagnoses should be considered (particular attention should be paid to other potentially life threatening causes of chest pain). As long as cardiac chest pain remains a possibility then the algorithm should be followed to completeness. 2.6 Blood tests in possible ACS- U&E, FBC, Hs-Troponin, random cholesterol and glucose. 2.7 Cardiac biomarker results (Troponin) must be interpreted in the context of the clinical presentation. Many non-cardiac conditions lead to elevated troponin and results must be interpreted within the clinical context. Patients with terminal kidney failure requiring dialysis can have a raised high sensitivity (hs) troponin T and careful assessment is required. An initial measurement of hs troponin T (hstnt) at presentation that is <5ng/L is a rule out for NSTEMI. If still considered to be cardiac chest pain, consider possible referral to the Cardiology Hot slot clinic after being given medical therapy of antiplatelet agent (aspirin), statin, beta blocker if not contraindicated and nitrate (Isosorbide Mononitrate M/R 30 mg). An initial measurement of hs troponin T (hstnt) at presentation that is 52ng/L is a rule in for NSTEMI. Admit to a monitored bed and refer to cardiology. Any patient with hs troponin T measurement that is between 5 and 51: 1. With intermediate risk factors, (please see ESC table 2 at the end of the document) requires admission to a Cardiology ward. Acute Coronary Syndrome Guidelines 7 of 18

8 2. Without Intermediate risk factors repeat hs troponin at 3 hours after 1 st troponin and if i. 5, admit AMU and refer to Cardiology. ii < 5 if still considered to be cardiac chest pain, consider possible referral to the Cardiology Hot slot clinic after being given medical therapy of antiplatelet agent (aspirin), statin, beta blocker if not contraindicated and nitrate (Isosorbide Mononitrate M/R 30 mg). In a subset of patients (particularly with renal impairment) who fall under the rule in with Troponin >52 ng/l, it may be useful to take a serial 3 hour sample to improve the specificity for ACS. 2.8 Diagnosis Patients with Non-ST Elevation Acute Coronary Syndromes (NSTEACS) can be broadly separated into: 1. Definite NSTEMI (Cardiac chest pain with Hs-Troponin elevation and/or dynamic ECG changes). 2. Definite Unstable Angina (On-going cardiac chest pain at rest with/without dynamic ECG changes without Hs-Troponin rise). 3. Possible NSTEMI (Atypical symptoms with Hs-Troponin elevation and/or dynamic ECG changes). 4. Possible Unstable Angina (On-going atypical symptoms with/without dynamic ECG changes without Hs-Troponin rise). NSTEMI Unstable angina Possible NSTEMI Possible unstable angina Likely Non cardiac Typical Symptoms ECG changes +/- +/- +/- +/- - TnT-hs rise Time of onset of chest pain and troponin Patients with acute onset of chest pain for 3 hours should be managed according to the pathway mentioned above. In those patients with onset of chest pain <3 hours, take the hs troponin at 3 hours and follow pathway Initial Management of Patients with ACS in Emergency Department Give Aspirin 300mg oral stat (if not already given). The second oral antiplatelet agent will be decided by the cardiology team only after review. The three choices available at SWBH are: Clopidogrel, Prasugrel and Ticagrelor. Acute Coronary Syndrome Guidelines 8 of 18

9 If ongoing chest pain and no contra-indications, give oxygen, GTN spray 1-2 sprays PRN,, morphine, metoclopramide (antiemetic) 10mg TDS IV as required and contact oncall cardiology SpR. Patients with recent PCI or cardiac surgery with cardiac chest pain should be discussed with the on-call cardiology registrar. Acute stent thrombosis is a medical emergency. If the diagnosis is not definite or other medical issues predominate then patient should be transferred to AMU following senior review. 3 MANAGEMENT IN ACUTE MEDICAL UNIT (AMU) 3.1 Daily cardiology ward rounds occur on both sites. The initial management of ACS by the acute medical team will be identical on both sites. Patients presenting to Sandwell requiring coronary angiography will be transferred to City Hospital following cardiology review within 48 hours. 3.2 A 12-lead ECG should be repeated on admission to AMU and the next morning. This should be reviewed and reported by a practitioner competent in ECG interpretation. A 12-lead ECG must also be repeated in the presence of recurrent symptoms. 3.3 If high-risk ECG changes (See 2.3) occur at any stage during admission to AMU, discuss immediately with the cardiology registrar. 3.4 If a diagnosis of definite NSTEMI is made (Hs-Troponin rise) then admit to monitored bed on AMU and refer to cardiology post-take ward round. If on-going symptoms then discuss with on-call cardiology registrar. 3.5 Risk Stratification in NSTEACS All patients with suspected NSTEACS (NSTEMI or UA) must have their GRACE Score calculated and documented for risk stratification purposes. The GRACE score is a risk stratification tool and must not be used to help make a diagnosis of ACS. For smartphone users, there is a free app available. Otherwise, For patients with definite/possible NSTEACS with GRACE 140 or other high risk features (table 2), please call the Cardiology SpR on call and send a troponin. Patients with GRACE score >109 to <140 are considered intermediate risk and should be admitted to a Cardiology ward. In the presence of on-going symptoms contact the oncall cardiology registrar. Other intermediate risk criteria include presence of Diabetes Mellitus, CKD with egfr<60ml/minute, LVEF <40% or heart failure, post-infarction angina, prior PCI and prior CABG. In the presence of on-going or definite cardiac symptoms then an inpatient cardiology referral is recommended. GRACE is not a diagnostic tool and is not predictive of angiographic findings. Acute Coronary Syndrome Guidelines 9 of 18

10 If symptoms resolved and no worrying features then the patient could be referred to an outpatient HOT SLOT cardiology clinic to be seen within 2 weeks. Automatic requesting of myoperfusion scanning by acute physicians is no longer recommended. 3.6 Management of NSTEACS on AMU pending transfer to cardiology ward Patients with definite NSTEMI or high-risk NSTEACS benefit from coronary angiography and early revascularisation. Whilst awaiting transfer to the cardiac wards in City Hospital patients should be continuously monitored if definite NSTEMI or high risk NSTEACS (See 3.4/3.5). Drug therapy as per 2.9 but do not repeat loading dose of aspirin or second antiplatelet agent, if already given previously. Ensure on regular maintenance dose of dual antiplatelet therapy. 3.7 Fondaparinux If troponin is elevated or on-going pain with no contraindications, give subcutaneous fondaparinux immediately after diagnosis confirmed (2.5mg subcutaneous daily if egfr >20 ml/min). Cautions: 1. Bleeding risk is high in elderly patients and should be used with caution. 2. Do not give on day of coronary angiography. 3. If egfr< 20ml/minute, consider enoxaparin 1mg/kg daily and seek expert advice/renal review. 4. Switching from Enoxaparin to Fondaparinux: i) If therapeutic enoxaparin has already been given: Stop enoxaparin and give fondaparinux dose when the next enoxaparin dose is due. ii) If prophylactic enoxaparin has been given: Stop enoxaparin and give fondaparinux as needed irrespective of the time the dose of enoxaparin dose was given. 3.8 Patients on anticoagulants ACS patients on warfarin: i. Omit warfarin if not mandatory (i.e. for AF), start fondaparinux when INR <2.0 ii. Continue warfarin if mandatory (e.g. mechanical valve), do not prescribe fondaparinux ACS patients on NOAC (Novel Oral Anti-Coagulants): i) On apixaban: Stop apixaban and start fondaparinux 12 hours after the last dose of apixaban Acute Coronary Syndrome Guidelines 10 of 18

11 ii) On rivaroxaban: Stop rivaroxaban and start fondaparinux 24 hours after the last dose of rivaroxaban iii) On dabigatran: Creatinine Clearance >30ml/min, start fondaparinux 12 hours after last dabigatran dose. Creatinine Clearance 30ml/min, start fondaparinux 24 hours after last dabigatran dose 3.9 Other medication Prescribe an oral beta-blocker (Bisoprolol is first line) provided no contraindications to beta-blockade (e.g bronchospasm, acute pulmonary oedema, bradycardia or heart block). Titrate bisoprolol as tolerated. Prescribe Glyceryl Trinitrate Spray 1-2 sprays sublingually as required provided no contraindications. Intravenous nitrates (Isosorbide Dinitrate) 2-10mg/hour if persistent or recurrent pain please remember to alert the on-call cardiology registrar if pain on-going. Consider starting Atorvastatin 80mg daily in all patients provided no contraindications or renal impairment. Consider ACE Inhibitor (Ramipril or perindopril) if no contraindications particularly in NSTEMI or if heart failure present. Titrate ACE inhibitor as tolerated Risk criteria mandating invasive strategy in NSTE-ACS Very-high-risk criteria Haemodynamic instability or cardiogenic shock Recurrent or ongoing chest pain refractory to medical treatment Life-threatening arrhythmias or cardiac arrest Mechanical complications of MI Acute heart failure Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation High-risk criteria Rise or fall in cardiac troponin compatible with MI Dynamic ST- or T-wave changes (symptomatic or silent) GRACE score >140 Intermediate-risk criteria Diabetes mellitus CKD (egfr<60) LVEF <40% or congestive heart failure Early post-infarction angina Prior PCI Prior CABG GRACE risk score >109 and <140 Low-risk criteria Any characteristics not mentioned above Acute Coronary Syndrome Guidelines 11 of 18

12 4. MANAGEMENT IN CARDIOLOGY WARD (D5/D7) 4.1 Review diagnosis as per 2.8. Repeat ECG on arrival to cardiac ward and if further chest pain. See table 2 for risk criteria mandating invasive strategy (from ESC guidelines 2015) 4.2 Review medication ensure on regular oral medication. Ensure patients with a diagnosis of NSTEMI or unstable angina have been loaded with aspirin and second antiplatelet agent(see appendix 3) and on maintenance dose. Ensure on therapeutic dose of fondaparinux and other medication (refer 3.7). Fondaparinux must NOT be given if the patient may be taken to the catheter lab that day if in doubt, wait for the daily morning consultant ward round. LMWH is usually no longer necessary post - PCI (operator discretion). If prolonged stay in hospital is likely consider prophylactic dose of enoxaparin. If tablets are not ingested because of vomiting, repeat loading dose if required. Figure 1: Reduced cumulative hazard with Fondaparinux compared to enoxaparin (OASIS-5) 4.3 Consider IV beta blocker (metoprolol 5 mg over 3-5 minutes) if patient still has angina, and is tachycardic (HR>100 bpm) with SBP>140 mmhg on monitor with no features of heart failure or bronchospasm. Discuss with consultant cardiologist if IV beta blockers to be given. 4.4 Ensure GRACE risk score documented. If invasive management is appropriate then this should be performed within 24 hours of admission to cardiac ward. Emergency coronary angiography may be appropriate if high-risk features are present or ongoing pain. Acute Coronary Syndrome Guidelines 12 of 18

13 Figure Consider initiating tirofiban on the cardiology ward in high-risk patients particularly those with on-going pain. Discuss with Consultant Cardiologist first. 4.6 Special Groups: a. Elderly (>80 years): Consideration for PCI with stent and subsequent dual antiplatelet therapy should take into account higher risk for bleed. b. Diabetes: Acute BM control with insulin sliding scale should be initiated. There is some evidence to suggest that Prasugrel may be better than Clopidogrel. c. Chronic renal failure: In patients listed for angiography pre hydration with IVI normal saline, if no heart failure. Appropriate adjustment of anticoagulant and glycoprotein IIb/IIIa inhibitors should be made in those with egfr < 30ml/min (stage 4/5 CKD).Nacetylcysteine is no longer recommended. d. Atrial Fibrillation: Anticoagulated patients receiving stents should be treated with triple therapy for a period. See flow-chart below from 2014 ESC Guidelines: Dose of aspirin used in the UK is 75mg daily. Refer Figure below Acute Coronary Syndrome Guidelines 13 of 18

14 5. REFERENCES 1. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal 2015; 37: Prasugrel versus clopidogrel in patients with acute coronary syndromes. Wiviott et al. N Engl J Med. 2007;357: Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel Thrombolysis in Myocardial Infarction 38. Wiviott SD et al. Circulation 2008; 118(16): Ticagrelor versus clopidogrel in patients with acute coronary syndromes. Wallentin et al. N Eng J Med. 2009; 361(11); NICE Diagnostic Guidance (DG15 October 2014) Myocardial infarction (acute): Early rule out using high-sensitivity troponin tests. 6. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). ACT Investigators. Circulation 2011; 124(11): NICE NSTEMI and Unstable Angina guidelines: Acute Coronary Syndrome Guidelines 14 of 18

15 8. Early versus delayed invasive intervention in acute coronary syndromes. Mehta et al. New Eng J Med. 2009; 360 (21); Lip GYH, Windecker S, Huber K, Kirchhof P, Marin F, Ten Berg J, et al. Management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting With Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary or Valve Interventions: A joint Consensus Document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association [EHRA], European Association of Percutaneous Cardiovascular Interventions [EAPCI] and European Association of Acute Cardiac Care [ACCA]. Endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes (The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators) NEJM 2006; 354: Bhatt DL, Stone GW, Mahaffey KW, Gibson MC et al, Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events (for the CHAMPION PHOENIX investigators). NEJM 2013; 368: Summary of Product Characteristics. Fondaparinux. Available from (accessed 26th July 2016) 13. Summary of Product Characteristics. Cangrelor. Available from (accessed 26th July 2016) 14. Summary of Product Characteristics. Apixaban. Available from (accessed 26th July 2016) 15. Summary of Product Characteristics. Rivaroxaban. Available from (accessed 26th July 2016) 16. Summary of Product Characteristics. Dabiagtran. Available from (accessed 26th July 2016) 17. Hellerslia, V and Mehta, P (2014) Transition of Oral anticoagulants Hospital Pharmacy. Available from (accessed 26th July 2016) Acute Coronary Syndrome Guidelines 15 of 18

16 Appendix I Glycoprotein IIb / IIIa Inhibitors For use only after review by cardiology SpR or consultant Tirofiban intravenous infusion, initially 400 nanogram per kg per minute for 30 minutes, followed by 100 nanogram per kg per minute for at least 48 hours (continue during and for 12 to 24 hours after PCI if carried out). Weight related nomogram available in packaging. Abciximab as per nomogram available in packaging. Abciximab use is limited to catheter laboratory only. Contraindications to GPIIb/IIIa inhibitors Abnormal bleeding or stroke within 30 days Haemorrhagic stroke at any time/ intracranial disease (e.g. aneurysm, neoplasm, ateriovenous malformation) Severe hypertension (systolic>180, diastolic>110 mmhg) Haemorrhagic diathesis, increased INR/APTT, thrombocytopenia Cautions Renal or hepatic impairment (avoid if severe) Major surgery / trauma within 3 months (avoid within 6 weeks) Traumatic/protracted CPR Puncture of non-compressible vessels within 24 hours Organ biopsy or lithotripsy within last 2 weeks; risk of bleeding including active peptic ulcer within 3 months, uncontrolled severe hypertension, acute pericarditis, aortic dissection, haemorrhagic retinopathy, vasculitis, haematuria, faecal occult blood, elderly, low body-weight; severe heart failure, cardiogenic shock, anaemia;; concomitant drugs that increase risk of bleeding (including within 48 hours of thrombolytic administration); monitor platelet count, haemoglobin and haematocrit before treatment, 2 6 hours after start of treatment and then at least once daily; discontinue if thrombolytic therapy, intraaortic balloon pump or emergency cardiac surgery necessary; discontinue immediately if serious or uncontrollable bleeding occurs Monitoring Tirofiban -Monitor platelets and Hb before treatment, 2 to 6 hours after start and daily thereafter. Abciximab measure baseline prothrombin time, activated clotting time, activated partial thromboplastin time, platelet count, haemoglobin and haematocrit; monitor haemoglobin and haematocrit 12 hours and 24 hours after start of treatment and platelet count 2 4 hours and 24 hours after start of treatment Discontinue if thrombolysis, or emergency surgery required. Discontinue immediately if serious bleeding uncontrolled by pressure occurs Acute Coronary Syndrome Guidelines 16 of 18

17 Appendix II Cangrelor (Intravenous PY212 Inhibitor) For use only after review by cardiology SpR or consultant Cangrelor is administered as an intravenous injection via a separate cannula, 30 micrograms/kg as a bolus dose, immediately followed by intravenous infusion, 4 micrograms/kg/minute; start treatment before percutaneous coronary intervention and continue infusion for at least 2 hours or for the duration of intervention if longer; max. duration of infusion 4 hours Indication: Cangrelor is licensed for use in combination with aspirin, for the reduction of thrombotic cardiovascular events in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who have not received treatment with oral clopidogrel, prasugrel or ticagrelor prior to the procedure and in whom oral therapy with these drugs is not suitable Patients should be transitioned to oral P2Y 12 therapy for chronic treatment. For transition, a loading dose of oral P2Y 12 therapy (clopidogrel, ticagrelor or prasugrel) should be administered immediately following discontinuation of cangrelor infusion. Alternatively, a loading dose of ticagrelor or prasugrel, but not clopidogrel, may be administered up to 30 minutes before the end of the infusion. Contra-indications: active bleeding or patients at increased risk of bleeding e.g impaired haemostasis, irreversible coagulation disorders, major surgery or trauma or uncontrolled hypertension; history of stroke or transient ischaemic attack. Cautions: disease states associated with increased bleeding risk; concomitant use of drugs that increase risk of bleeding, severe renal impairment Reporting of suspected adverse reactions Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: Acute Coronary Syndrome Guidelines 17 of 18

18 Appendix III Antiplatelet therapy in addition to Aspirin (Thienopyridines) Summary of antiplatelet agents All antiplatelet agents increase the risk of bleeding and must not be used if active bleeding is suspected. Its use in patients on chronic anticoagulation therapy must be considered very cautiously and should be in line with latest ESC recommendations. Clopidogrel is a second generation thienopyridine and used to be the standard second antiplatelet. It is still commonly used. However, clopidogrel resistance is a known problem in a significant proportion of patients. It also requires conversion to its active metabolite by the liver, which delays its onset of action especially in ST-elevation myocardial infarction. It binds platelets irreversibly. Prasugrel is a third generation thienopyridine and in the TRITON-TIMI 38 trial reduced major adverse cardiovascular events (MACE) compared to clopidogrel without affecting mortality. It is associated with an increased risk in bleeding compared to clopidogrel but has more predictable pharmacokinetics and is more potent. It binds platelets irreversibly. Prasugrel should not be used in patients who have had previous strokes. In patients older than 75 years old or <60kg in weight, either prescribe 5mg od or alternatively, consider ticagrelor. Ticagrelor is a newer class of antiplatelet. It is an ADP-receptor antagonist and binds a different site of the P2Y12 receptor on the platelet. It binds the receptor reversibly. It is an active drug (not requiring conversion), as is its metabolite. In the PLATO study, Ticagrelor reduced mortality compared to clopidogrel in ACS patients with a reduced risk of bleeding. Known side effects include transient dyspnoea, ventricular pauses and increase in creatinine levels. There has been no comparative trials on TicagrelorvsPrasugrel to date. Agreed use at SWBH at the discretion of consultant cardiologist. Acute coronary syndrome ST elevation myocardial infarction Post PCI for stable angina Post PCI for ACS and STEMI Clopidogrel Prasugrel Ticagrelor Acute Coronary Syndrome Guidelines 18 of 18