Management of Non-ST Elevation Myocardial Infarction (NSTE-ACS) PDF 2021

CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS)...

CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021  Identify patients with NSTE-ACS and STEMI based on history and characteristic ECG changes after consultation with the ED physician/ medical officer  Assess, stabilise and monitor the patient’s hemodynamics continuously prior to and during transfer Key Recommendations 5:  Public awareness about heart disease should be increased so that individuals will seek appropriate treatment early, thus reducing time from symptom onset to FMC.  If the person is suspected to have an ACS and is not on regular aspirin with no history of allergy, 300mg aspirin should be administered. Soluble and chewable aspirin formulations are preferable to solid aspirin either chewed or swallowed. Key Recommendations 6:  Ambulance responders should be trained and equipped to perform an ECG.  If the ECG shows STEMI or the patient with NSTE-ACS has ongoing/ recurrent chest pain, they should be considered for immediate transfer to a PCI-capable hospital. High-risk unstable patients should be taken to the nearest hospital for stabilization first. 7. IN - HOSPITAL MANAGEMENT 7.1 Emergency Department When the patient with suspected ACS reaches the emergency department, evaluation and initial management should be prompt. Patients can be either triaged to the red or yellow zone according to the Malaysian Triage Scale. A quick targeted history should be taken, and vital signs noted.  A 12 lead ECG should be taken within 10 minutes of the patient’s arrival in the emergency department.127,128 This should be compared with prehospital ECGs or that taken earlier if available. Based on the initial clinical evaluation, the patient may have:  Definite STEMI  NSTE-ACS with ongoing chest pain. If the initial ECG does not show ST elevation but the patient is suspected of having a STEMI in view of the prolonged ischaemic-type chest pain of > 30 minutes and recurrent/on going chest pains, the following steps may be taken: 66 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021  Repeating the ECG at 15-minute intervals to detect evolving changes of ischemia/infarction.  The use of additional chest leads may be helpful in detecting STEMI at uncommon and difficult to detect sites: Additional posterior chest wall leads (V7-V9) can detect a posterior MI (circumflex occlusion).10,129-132 Right precordial leads (V3R and V4R) may be necessary to identify concomitant Right Ventricular (RV) infarction in the presence of an inferior wall MI.10,133  If STEMI has been excluded, the patient may fall into 3 categories as outlined in Section 5.1:  Very low likelihood to be ACS or have an alternative cause for their symptoms. These can be treated accordingly and be considered for discharge.  Definite NSTE-ACS  Possible or suspected NSTE-ACS - In these individuals the HEART Score (or modified HEART score) or TIMI score should be calculated, the cTn, preferably hs-cTn measured and the “rule out protocol” Flowchart 1, page 35 be used. In patients with NSTE-ACS, the following should be done:  Venous access established and blood taken for measurement of cardiac biomarkers (cTn-preferably hs cTn).  The following are instituted: I,A  Aspirin (300mg) if not taken prior to arrival.124,125  Oxygen is administered in patients with hypoxemia.134-137 I,A SpO2 ≤ 90% IIa,B SpO2 > 90 - ≤ 95%  In the presence of ongoing chest pain, GTN sublingual tablet (0.3- 0.6 mg) I,C or spray (0.4-0.8 mg) should be administered every 5 minutes for up to three doses if no contraindications exists (such as hypotension). Nitrates only help with symptom relief.  If symptoms are unrelieved: Serial ECGs should be taken every 10-15minutes until the patient is pain free and compared with pre-existing ECGs to look for changes of STEMI. Assess the need for i.v. GTN and/or i.v. morphine at 2-5 mg by slow bolus injection every 5-15 minutes as necessary. Watch for adverse events - hypotension and respiratory depression. Antiemetic (i.v. metoclopramide 10 mg or promethazine 25mg) should be given with morphine and 8-hourly as necessary. Morphine should be used cautiously.138 i.v. fentanyl 50mcg in titrated doses may also be considered. 67 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021 I,A  s.c. LMWH or s.c. fondaparinux should be given.139-143  In the presence of ongoing chest pains and/or hemodynamic instability, I,B urgent coronary angiography with view to revascularization should be considered if facilities are available.107,144-150 In patients with chest pain not due to ACS, other important clinical conditions should also be considered. Some of these can be life threatening. Non-ischemic cardiovascular causes of chest pain  Aortic dissection  Pulmonary embolism  Pericarditis and myocarditis Non-cardiovascular causes of chest pain  Gastrointestinal causes (e.g. gastro-esophageal reflux, oesophageal spasm, peptic ulcer, pancreatitis, biliary disease)  Musculoskeletal causes (e.g. costochondritis, cervical radiculopathy, fibrositis)  Pulmonary (e.g. pneumonia, pleuritis, pneumothorax)  Other etiologies (e.g. herpes zoster, panic attack) Key Recommendations 7:  Patients with NSTE-ACS should be given:  Aspirin 300 mg stat (if not given earlier)  And Oxygen if oxygen saturation < 95%  And GTN for ongoing or recurrent chest pains  And i.v. morphine with i.v. anti-emetics or fentanyl for ongoing chest pains  And s.c. low molecular weight heparin or fondaparinux  In the presence of ongoing chest pains and/or hemodynamic instability, urgent coronary angiography with view to revascularization should be considered.  In patients with recurrent/ ongoing chest pain not due to ACS, other important clinical conditions should also be considered. 7.2 Level of Care Following risk stratification as outlined in section 5.2, page 60 the patient may be admitted to:  Coronary care unit (CCU) - Very high risk and High-risk individuals  High dependency Unit - Moderate risk individuals  General ward - Low risk individuals Stable, low-risk NSTE-ACS may be managed appropriately on telemetry wards and result in a reduction in hospital costs and critical care capacity.151 68 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021 7.3. Pharmacotherapy In NSTE-ACS the commonest pathophysiology (Type 1 MI) is a ruptured or fissured plaque with superadded thrombosis leading to varying degrees of occlusion of the vessel. Thus, anti-thrombotic therapy (both antiplatelet and anticoagulant) plays a more important role in management than anti-ischemic agents. In Type 2 MI, the underlying etiology needs to be addressed. Anti-ischemic agents play a more important role than antiplatelets and antithrombotic agents. 7.3.1 Antiplatelet therapy 7.3.1.1 Acetylsalicylic acid (ASA/Aspirin)  Recommended loading dose: 300mg. This should be chewed or I,A crushed.124,125 Enteric-coated aspirin is not recommended as an initial loading dose because of its slow onset of action.  Maintenance dose: 75-100mg daily lifelong regardless of treatment strategy.152-154 III,B  An aspirin dose of 300-325mg daily is associated with an increased risk of gastrointestinal bleeding without greater efficacy.153,154 This was seen when aspirin was used alone and in combination with a P2Y12 inhibitor such a clopidogrel.155  For patients taking ticagrelor, the aspirin maintenance dose should be ≤100mg daily.156,157  Proton pump inhibitors (PPI) in combination with DAPT should be IIa,A considered for patients who are at high risk of gastrointestinal bleeds (i.e. history of gastrointestinal ulcer/haemorrhage, anticoagulant therapy, chronic NSAID/corticosteroid use or two or more of the following: age ≥65 years, dyspepsia, gastro-esophageal reflux disease, Helicobacter pylori infection, chronic alcohol use)158,159  In those patients allergic to aspirin, the available options include:  More potent P2Y12 inhibitors (ticagrelor or prasugrel) alone  Cilostazol with clopidogrel 160  Triflusal with clopidogrel 161,162  Aspirin desensitisation 163,164 69 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021 7.3.1.2 P2Y12 inhibitors (Appendix VII, page 99) These may be given as: I,A  A substitute to patients who are intolerant or allergic to aspirin.  As part of DAPT I,A The different P2Y12 inhibitors each have their own special characteristics that may prompt one being favoured over another in various circumstances. Recognising the characteristic differences in the agents can help with the choice of the best agent for individual patients. (Appendix VII, page 99) Both ticagrelor and prasugrel have similar efficacy and bleeding rates when used as part of DAPT at 7 days, 1 month and 1 year.165-168 A recent study found prasugrel to be superior to ticagrelor in reduction of death, MI or stroke without an increase in major bleeding.169 7.3.1.2.1 Clopidogrel I,A  Loading dose: 300 to 600mg, maintenance dose: 75mg daily.152,170  The benefits of long term clopidogrel when added to aspirin was seen in I,A NSTE-ACS patients treated medically, those undergoing PCI or coronary artery bypass grafting.152,171,172  Clopidogrel versus prasugrel. In ACS patients:  undergoing PCI, prasugrel significantly reduced MACE but there was an increase in severe bleeding complications when compared to clopidogrel.173  who are medically managed, MACE and severe bleeding rates were similar between prasugrel and clopidogrel groups.174  Clopidogrel versus ticagrelor. In ACS patients:  with or without PCI, ticagrelor significantly reduced MACE compared to clopidogrel and severe bleeding rates were similar.156  The use of clopidogrel for up to a year as part of a strategy of DAPT was IIa,B found to be cost effective.175 7.3.1.2.2 Prasugrel  Prasugrel may be considered as a second antiplatelet agent after the I,B coronary angiogram has been performed. (No pre-treatment)  Loading dose: 60mg, maintenance dose: 10mg/day.173,176  It is not recommended due to a higher risk of major bleeding in patients III,A who are:173,176  > 75 years old or,  < 60kg weight or,  have prior history of transient ischemic attack or stroke.  It should be considered in patients who present with stent thrombosis IIa,B despite compliance with clopidogrel therapy.177 70 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021 7.3.1.2.3 Ticagrelor I,B  Loading dose: 180mg, maintenance dose: 90mg twice daily.156,178  When compared to clopidogrel, ticagrelor resulted in a significant reduction in cardiac end points in patients undergoing an early invasive or medically treated strategy.156,178  Potential drawback is dyspnoea and transient ventricular pauses during the first week. This was rarely associated with symptoms or need for a pacemaker. Caution should be exercised in patients with heart block. 7.3.1.3 Timing of Initiation of DAPT  When given as part of DAPT, the timing of initiation of the second antiplatelet agent is not clear. There are a few randomised trials directly comparing pre-treatment with initiation at the time of angiography.179  Unlike in STEMI, NSTE-ACS patients are a heterogenous group and include patients with multivessel disease who may be more suitable for coronary artery bypass surgery or maybe even have normal coronaries.  Although most Guidelines advocate pre-treatment, no recommendation for or against pre-treatment with these agents can be formulated because of the lack of trial data. I,C  The exact timing is left to the clinical judgement of the attending physician. 7.3.1.4 Duration of DAPT  In NSTE-ACS patients, with or without PCI, DAPT is recommended for I,A up to 12 months unless there are contraindications such as excessive risk of bleeds.152,171,180-182  In ACS patients who underwent PCI and at high risk of bleeding, DAPT I,B maybe continued for 3 to 6 months.181,182  Continuing DAPT for more than 12 months significantly reduces MACE IIb,B at the expense of an increase in major bleeding. 183,184 7.3.1.5 Switching a potent P2Y12 to clopidogrel  In patients with NSTE-ACS undergoing PCI, ticagrelor or prasugrel is usually preferred to clopidogrel.  However, many patients may need to be switched to clopidogrel due to an increased risk of bleeding, other side effects (eg dyspnoea with ticagrelor) and costs. 165,185-188  The following approaches maybe considered:165,185-188  Those on ticagrelor: De-escalate to clopidogrel with a loading dose of 300-600mg followed by 75mg daily, to be initiated at the time of the next scheduled ticagrelor dose. 71 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021  Those on prasugrel:185 De-escalate directly to clopidogrel 75mg (without a loading dose) at the time of the next scheduled prasugrel dose. 7.3.1.6 Glycoprotein (GP) IIb/IIIa Inhibitors (Appendix VIII, page 100)  These agents are no longer used pre-procedure/ “upstream” because IIb,B studies have not found this practice to be superior to the provisional selective use after angiography. It is also associated with an increased risk of bleeding.189,190  Their main use is in patients who have been found to have a large thrombus burden at the time of coronary angiography.  These agents include:  Abciximab  Tirofiban  Eptifibatide 7.3.2 Anticoagulant Therapy (Appendix IX, page 101) I,A  In NSTE-ACS patients managed medically, parenteral anticoagulation is recommended as soon as possible after the diagnosis.139,140,191  The type of agent used may vary depending on whether the patient is managed by an early invasive or a conservative approach, issues of cost and local practice.  The duration of anticoagulant therapy in patients treated medically would vary between 2-8 days. 7.3.2.1 Heparin This includes:  Unfractionated heparin (UFH) I,B  For high risk NSTE-ACS patients undergoing an early invasive approach, UFH had similar efficacy to enoxaparin.192,193  Low Molecular Weight Heparin (LMWH) - Enoxaparin I,A  It is best used in NSTE-ACS patients treated conservatively.141,194,195  In patients > 75 years of age and with renal impairment (serum creatinine I,B (Scr) > 200 µmol/L in women and > 250 µmol/L in men), UFH is preferable to LMWH.196 72 CLINICAL PRACTICE GUIDELINES MANAGEMENT OF NON-ST ELEVATION MYOCARDIAL INFARCTION (NSTE-ACS) 3RD EDITION 2021 7.3.2.2 Anti-Xa inhibitors This includes:  Fondaparinux 142,143 I,B  It is best used in NSTE-ACS patients treated conservatively.  It is associated with an increase in catheter-related thrombus and III,A coronary angiographic complications. Thus, it is not recommended as the sole anticoagulant during PCI.  If used in patients with NSTE-ACS and the patient requires an invasive strategy, UFH should be given during the procedure.  In patients with NSTE-ACS, fondaparinux was found to be more cost effective and associated with less short and midterm bleeding events compared with enoxaparin.197-199 Presently newer oral anti-Xa inhibitors are undergoing evaluation for ACS. A IIb,B meta-analysis showed that the addition of Direct Oral Ant-Coagulants (DOAC) to DAPT in patients with NSTE-ACS did not show any significant treatment effect at the risk of increased bleeding.200 7.3.3 Anti-ischemic Drug Therapy These agents may be given either for relief of ischemia (symptoms) or for improvement of prognosis. 7.3.3.1 β-blockers (Appendix X, page 102)  There is limited randomised trials addressing the efficacy of β-blockers in NSTE-ACS.201,202  β-blockers should be given to patients with heart failure and/or LV I,A dysfunction (LVEF < 40%), continuing angina and/ or ischemia.203-207  There is limited evidence to administer it routinely in all patients.208-211 IIb,A  In the absence of contraindications, β-blockers may be administered after the patient has been stabilized and prior to hospital discharge.202  Relative contraindications for β-blockers include:  Patients with marked first-degree AV block (PR interval > 0.24s).  Second - or third-degree AV block.  History of bronchial asthma  Severe peripheral arterial disease  Acute decompensated LV dysfunction  Cardiogenic shock.  For patients who have LVEF 0.8 - medical therapy Key Messages 8#:  An early as opposed to a delayed invasive strategy is safe and associated with a lower risk of refractory ischemia and a shorter duration of hospital stay. Key Recommendations 10:  The selection of the optimal timing of invasive coronary angiography and revascularization should be guided by the individual’s risk for a MACE. (Table 2, page 38) Patients at:  Very high risk should undergo an immediate invasive strategy ( 70years had elevated troponins.285 The conventional cut-off value (99th percentile: 0.014 ng/mL) provided low specificity, particularly in older adults.286 80