MI MANAGEMENT: ACS Guideline Review. Ben Ochoa BS, RCIS, RCS

Transcription

1 MI MANAGEMENT: ACS Guideline Review en Ochoa S, RCIS, RCS

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3 Objectives Discuss management of patients with Non-ST-Elevation Acute Coronary Syndromes. Discuss management of patients with ST-Elevation Acute Coronary Syndromes Discuss Hemodynamic management considerations with ACS patients. Discuss Drug management with ACS patients.

4 Guideline Overview

5 ACS Overview Refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction due to an abrupt reduction in coronary blood flow

6 ACS Overview Presentation Ischemic Discomfort ACS Working Dx ECG No ST Elevation NSTE-ACS ST Elevation Cardiac iomarker UA NSTEMI* STEMI* Final Dx Unstable Angina Myocardial Infarction NQMI QwMI Noncardiac Etiologies

7 NSTEMI Management

8 NSTEMI Management Initial Evaluation/Management Early Hospital Care Myocardial Revascularization Special Patient Recommendations

9 Initial Evaluation/Management General Patients with suspected ACS should be risk stratified based on the likelihood of ACS and adverse outcome(s) to decide on the need for hospitalization and assist in the selection of treatment options. I

10 Initial Evaluation/Management Emergency Department or Outpatient Facility Presentation Patients with suspected ACS and high-risk features such as continuing chest pain, severe dyspnea, syncope/presyncope, or palpitations should be referred immediately to the ED and transported by emergency medical services when available. Patients with less severe symptoms may be considered for referral to the ED, a chest pain unit, or a facility capable of performing adequate evaluation depending on clinical circumstances. I IIb C C

11 Initial Evaluation/Management Prognosis: Early Risk Stratification In patients with chest pain or other symptoms suggestive of ACS, a 12-lead ECG should be performed and evaluated for ischemic changes within 10 minutes of the patient s arrival at an emergency facility. If the initial ECG is not diagnostic but the patient remains symptomatic and there is a high clinical suspicion for ACS, serial ECGs (e.g., 15- to 30-minute intervals during the first hour) should be performed to detect ischemic changes. Serial cardiac troponin I or T levels (when a contemporary assay is used) should be obtained at presentation and 3 to 6 hours after symptom onset all patients who present with symptoms consistent with ACS to identify a rising and/or falling pattern of values. I A I I C C

12 Initial Evaluation/Management Prognosis: Early Risk Stratification Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponin levels on serial examination when I A changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS. Risk scores should be used to assess prognosis in patients with NSTE-ACS. I A Risk-stratification models can be useful in management. IIa

13 Initial Evaluation/Management TIMI Risk Scor e Prognosis: Early Risk Stratification Thrombolysis in Myocardial Infarction (TIMI) Risk Score All-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 d After Randomization, %

14 Initial Evaluation/Management Prognosis: Early Risk Stratification GRACE ACS Risk and Mortality

15 Initial Evaluation/Management Prognosis: Early Risk Stratification It is reasonable to obtain supplemental electrocardiographic leads V 7 to V 9 in patients whose initial ECG is nondiagnostic and who are at IIa intermediate/high risk of ACS. Continuous monitoring with 12-lead ECG may be a reasonable alternative in patients whose initial ECG is nondiagnostic and who are at intermediate/high risk IIb of ACS. Measurement of -type natriuretic peptide or N- terminal pro -type natriuretic peptide may be considered to assess risk in patients with suspected ACS. IIb

16 Initial Evaluation/Management Cardiac iomarkers: Diagnosis Cardiac-specific troponin (troponin I or T when a contemporary assay is used) levels should be measured at presentation and 3 to 6 hours after symptom onset in all patients who present with symptoms consistent with ACS to identify a rising and/or falling pattern. Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponins on serial examination when electrocardiographic changes and/or clinical presentation confer an intermediate or high index of suspicion for ACS. If the time of symptom onset is ambiguous, the time of presentation should be considered the time of onset for assessing troponin values. With contemporary troponin assays, creatine kinase myocardial isoenzyme (CK-M) and myoglobin are not useful for diagnosis of ACS. I I I III: No enefit A A A A

17 Initial Evaluation/Management Cardiac iomarkers: Prognosis The presence and magnitude of troponin elevations are useful for short- and long-term prognosis. I It may be reasonable to remeasure troponin once on day 3 or day 4 in patients with MI as an index of infarct size and dynamics of necrosis. Use of selected newer biomarkers, especially -type natriuretic peptide, may be reasonable to provide additional prognostic information. IIb IIb

18 Early Hospital Care Standard Medical Therapies Oxygen Recommendation Class Level Supplemental oxygen should be administered to patients with NSTE-ACS with arterial oxygen saturation less than 90%, respiratory distress, or other high-risk features of hypoxemia. I C

19 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: Analgesic Therapy In the absence of contraindications, it may be reasonable to administer morphine sulfate intravenously to patients with NSTE-ACS if there is continued ischemic chest pain despite treatment with IIb maximally tolerated anti-ischemic medications. Nonsteroidal anti-inflammatory drugs (NSAIDs) (except aspirin) should not be initiated and should be discontinued during hospitalization for NSTE-ACS because of the increased risk of MACE associated with their use. III: Harm

20 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: eta-adrenergic lockers Oral beta-blocker therapy should be initiated within the first 24 hours in patients who do not have any of the following: 1) signs of HF, 2) evidence of low-output state, 3) increased risk for cardiogenic shock, or 4) other contraindications to beta blockade (e.g., PR interval >0.24 second, second- or thirddegree heart block without a cardiac pacemaker, active asthma, or reactive airway disease). In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function, it is recommended to continue beta-blocker therapy with 1 of the 3 drugs proven to reduce mortality in patients with HF: sustained-release metoprolol succinate, carvedilol, or bisoprolol. I I A C

21 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: eta-adrenergic lockers Patients with documented contraindications to beta blockers in the first 24 hours of NSTE-ACS should be reevaluated I C to determine their subsequent eligibility. It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS. IIa C Administration of intravenous beta blockers is III: potentially harmful in patients with NSTE-ACS who have Harm risk factors for shock.

22 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: Calcium Channel lockers In patients with NSTE-ACS, continuing or frequently recurring ischemia, and a contraindication to beta blockers, a nondihydropyridine calcium channel blocker (CC) (e.g., verapamil or diltiazem) should be given as initial therapy in the absence of clinically significant LV dysfunction, increased risk for cardiogenic shock, PR interval greater than 0.24 second, or second- or thirddegree atrioventricular block without a cardiac pacemaker. I Oral nondihydropyridine calcium antagonists are recommended in patients with NSTE-ACS who have recurrent ischemia in the absence of contraindications, after appropriate use of beta blockers and nitrates. I C

23 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: Calcium Channel lockers CCs are recommended for ischemic symptoms when beta blockers are not successful, are I C contraindicated, or cause unacceptable side effects. Long-acting CCs and nitrates are recommended in patients with coronary artery spasm. I C Immediate-release nifedipine should not be III: administered to patients with NSTE-ACS in the absence Harm of beta-blocker therapy.

24 Early Hospital Care Standard Medical Therapies Anti-Ischemic and Analgesic Medications: Cholesterol Management High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and no I A contraindications to its use. It is reasonable to obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. IIa C

25 Early Hospital Care Inhibitors of Renin-Angiotensin-Aldosterone System ACE inhibitors should be started and continued indefinitely in all patients with LVEF less than 0.40 and in those with hypertension, diabetes mellitus, or stable I A CKD (Section 7.6), unless contraindicated. ARs are recommended in patients with HF or MI with LVEF less than 0.40 who are ACE inhibitor intolerant. I A Aldosterone blockade is recommended in patients post MI without significant renal dysfunction (creatinine >2.5 mg/dl in men or >2.0 mg/dl in women) or hyperkalemia (K >5.0 meq/l) who are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF 0.40 or less, diabetes mellitus, or HF. I A

26 Early Hospital Care Inhibitors of Renin-Angiotensin-Aldosterone System ARs are reasonable in other patients with cardiac or other vascular disease who are ACE inhibitor intolerant. IIa ACE inhibitors may be reasonable in all other patients with cardiac or other vascular disease. IIb

27 Algorithm for Management of Patients With Definite or Likely NSTE-ACS

28 Algorithm for Management of Patients With Definite or Likely NSTE-ACS NSTE-ACS: Definite or Likely Ischemia-Guided Strategy Early Invasive Strategy Initiate DAPT and Anticoagulant Therapy 1. ASA (Class I; LOE: A) 2. P2Y 12 inhibitor (in addition to ASA) (Class I; LOE: ) : Clopidogrel or Ticagrelor 3. Anticoagulant: UFH (Class I; LOE: ) or Enoxaparin (Class I; LOE: A) or Fondaparinux (Class I; LOE: ) Initiate DAPT and Anticoagulant Therapy 1. ASA (Class I; LOE: A) 2. P2Y 12 inhibitor (in addition to ASA) (Class I; LOE: ): Clopidogrel or Ticagrelor 3. Anticoagulant: UFH (Class I; LOE: ) or Enoxaparin (Class I; LOE: A) or Fondaparinux (Class I; LOE: ) or ivalirudin (Class I; LOE: ) Can consider GPI in addition to ASA and P2Y 12 inhibitor in high-risk (e.g., troponin positive) pts (Class IIb; LOE: ) Eptifibatide Tirofiban Medical therapy chosen based on cath findings

29 Factors Associated With Appropriate Selection of Early Invasive Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS Immediate invasive (within 2 h) Ischemiaguided strategy Early invasive (within 24 h) Delayed invasive (within h) Refractory angina Signs or symptoms of HF or new or worsening mitral regurgitation Hemodynamic instability Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy Sustained VT or VF Low-risk score (e.g., TIMI [0 or 1], GRACE [<109]) Low-risk Tn-negative female patients Patient or clinician preference in the absence of high-risk features None of the above, but GRACE risk score >140 Temporal change in Tn (Section 3.4) New or presumably new ST depression None of the above but diabetes mellitus Renal insufficiency (GFR <60 ml/min/1.73 m²) Reduced LV systolic function (EF <0.40) Early postinfarction angina PCI within 6 mo Prior CAG GRACE risk score ; TIMI score 2

30 Early Hospital Care Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy Non enteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients with NSTE-ACS without contraindications as soon as possible after I A presentation, and a maintenance dose of aspirin (81 mg/d to 162 mg/d) should be continued indefinitely. In patients with NSTE-ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered. I

31 Early Hospital Care Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy A P2Y 12 inhibitor (either clopidogrel or ticagrelor) in addition to aspirin should be administered for up to 12 months to all patients with NSTE-ACS without contraindications who are treated with either an early invasive or ischemia-guided strategy. Options include: Clopidogrel: 300-mg or 600-mg loading dose, then 75 mg daily Ticagrelor : 180-mg loading dose, then 90 mg twice daily I

32 Early Hospital Care Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTE-ACS Treated With an Initial Invasive or Ischemia-Guided Strategy It is reasonable to use ticagrelor in preference to clopidogrel for P2Y 12 treatment in patients with NSTE- ACS who undergo an early invasive or ischemiaguided IIa strategy. In patients with NSTE-ACS treated with an early invasive strategy and dual antiplatelet therapy (DAPT) with intermediate/high-risk features (e.g., positive troponin), a GP IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy. Preferred options are eptifibatide or tirofiban. IIb

33 Early Hospital Care Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include: Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with creatinine clearance [CrCl] <30 ml/min), continued for the duration of hospitalization or until PCI is performed. An initial intravenous loading dose is 30 mg. I A

34 Early Hospital Care Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS ivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic angiography or PCI, with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT. Fondaparinux: 2.5 mg SC daily, continued for the duration of hospitalization or until PCI is performed. I

35 Early Hospital Care Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-iia activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis. UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed. In patients with NSTE-ACS (i.e., without ST elevation, true posterior MI, or left bundle-branch block not known to be old), intravenous fibrinolytic therapy should not be used. I III: Harm A

36 Early Hospital Care Early Invasive and Ischemia: Guided Strategies An urgent/immediate invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in patients (men and women) with NSTE-ACS who have I A refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures). An early invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in initially stabilized patients with NSTE-ACS (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events. I

37 Early Hospital Care Early Invasive and Ischemia: Guided Strategies It is reasonable to choose an early invasive strategy (within 24 hours of admission) over a delayed invasive strategy (within 25 to 72 hours) for initially stabilized high-risk patients with NSTE-ACS. For those not at high/intermediate risk, a delayed invasive approach is reasonable. In initially stabilized patients, an ischemia-guided strategy may be considered for patients with NSTE-ACS (without serious comorbidities or contraindications to this approach) who have an elevated risk for clinical events. IIa IIb The decision to implement an ischemia-guided strategy in initially stabilized patients (without serious comorbidities or contraindications to this approach) may be reasonable after considering clinician and patient preference. IIb C

38 Early Hospital Care Early Invasive and Ischemia: Guided Strategies An early invasive strategy (i.e., diagnostic angiography with intent to perform revascularization) is not recommended in patients with: Extensive comorbidities (e.g., hepatic, renal, pulmonary failure, cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization. Acute chest pain and a low likelihood of ACS III: No enefit C C who are troponin-negative, especially women.

39 Algorithm for Management of Patients With Definite or Likely NSTE-ACS Therapy Effective Therapy Ineffective PCI With Stenting Initiate/continue antiplatelet and anticoagulant therapy 1. ASA (Class I; LOE: ) 2. P2Y 12 Inhibitor (in addition to ASA) : Clopidogrel (Class I; LOE: ) or Prasugrel (Class I; LOE: ) or Ticagrelor (Class I; LOE: ) 3. GPI (if not treated with bivalirudin at time of PCI) High-risk features, not adequately pretreated with clopidogrel (Class I; LOE: A) High-risk features adequately pretreated with clopidogrel (Class IIa; LOE: ) 4. Anticoagulant: Enoxaparin (Class I; LOE: A) or ivalirudin (Class I; LOE: ) or Fondaparinux as the sole anticoagulant (Class III: Harm; LOE: ) or UFH (Class I; LOE: ) CAG Initiate/continue ASA therapy and discontinue P2Y 12 and/or GPI therapy 1. ASA (Class I; LOE: ) 2. Discontinue clopidogrel/ticagrelor 5 d before, and prasugrel at least 7 d before elective CAG 3. Discontinue clopidogrel/ticagrelor up to 24 h before urgent CAG (Class I; LOE: ). May perform urgent CAG <5 d after clopidogrel/ticagrelor and <7 d after prasugrel discontinued 4. Discontinue eptifibatide/tirofiban at least 2-4 h before, and abciximab 12 h before CAG (Class I; LOE: ) Late Hospital/Posthospital Care 1. ASA indefinitely (Class I; LOE: A) 2. P2Y 12 inhibitor (clopidogrel or ticagrelor), in addition to ASA, up to 12 mo if medically treated (Class I; LOE: ) 3. P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor), in addition to ASA, at least 12 mo if treated with coronary stenting (Class I; LOE: )

40 Myocardial Revascularization Percutaneous Coronary Intervention Considerations Recommendation Class Level A strategy of multivessel PCI, in contrast to culprit lesion only PCI, may be reasonable in patients undergoing coronary revascularization as part of treatment for NSTE-ACS. IIb

41 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents Patients already taking daily aspirin before PCI should take 81 mg to 325 mg non enteric-coated aspirin I before PCI. Patients not on aspirin therapy should be given non enteric-coated aspirin 325 mg as soon as possible I before PCI. After PCI, aspirin should be continued indefinitely at a dose of 81 mg to 325 mg daily. I

42 Myocardial Revascularization PCI-Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents A loading dose of a P2Y 12 receptor inhibitor should be given before the procedure in patients undergoing PCI with stenting. Options include: A Clopidogrel: 600 mg or Prasugrel #: 60 mg or Ticagrelor : 180 mg I

43 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) not adequately pretreated with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI. I A

44 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents In patients receiving a stent (bare-metal stent or drugeluting stent [DES]) during PCI for NSTE-ACS, P2Y 12 inhibitor therapy should be given for at least 12 months. Options include Clopidogrel: 75 mg daily or Prasugrel #: 10 mg daily or Ticagrelor : 90 mg twice daily I

45 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents It is reasonable to choose ticagrelor over clopidogrel for P2Y 12 inhibition treatment in patients with NSTE-ACS treated with an early invasive strategy and/or coronary stenting. IIa It is reasonable to choose prasugrel over clopidogrel for P2Y 12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk of bleeding complications. In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) treated with UFH and adequately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban) at the time of PCI. IIa IIa

46 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Oral and Antiplatelet Agents After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses. If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y 12 inhibitor therapy after stent implantation, earlier discontinuation (e.g., <12 months) of P2Y 12 inhibitor therapy is reasonable. Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implantation. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack. IIa IIa IIb III: Harm C C

47 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: GP IIb/IIIa Inhibitors In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) and not adequately pretreated with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI. In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) treated with UFH and adequately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, doublebolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI. I IIa A

48 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Anticoagulant Therapy in Patients Undergoing PCI An anticoagulant should be administered to patients with NSTE-ACS undergoing PCI to reduce the risk of I C intracoronary and catheter thrombus formation. Intravenous UFH is useful in patients with NSTE-ACS undergoing PCI. I C ivalirudin is useful as an anticoagulant with or without prior treatment with UFH in patients with NSTE-ACS undergoing PCI. I

49 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Anticoagulant Therapy in Patients Undergoing PCI An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg SC) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PCI. If PCI is performed while the patient is on fondaparinux, an additional 85 IU/kg of UFH should be given intravenously immediately before PCI because of the risk of catheter thrombosis (60 IU/kg IV if a GP IIb/IIIa inhibitor used with UFH dosing based on the target-activated clotting time). In patients with NSTE-ACS, anticoagulant therapy should be discontinued after PCI unless there is a compelling reason to continue such therapy. I I I C

50 Myocardial Revascularization Antiplatelet and Anticoagulant Therapy: Anticoagulant Therapy in Patients Undergoing PCI In patients with NSTE-ACS undergoing PCI who are at high risk of bleeding, it is reasonable to use bivalirudin monotherapy in preference to the combination of UFH IIa and a GP IIb/IIIa receptor antagonist. Performance of PCI with enoxaparin may be reasonable in patients treated with upstream subcutaneous enoxaparin for NSTE-ACS. IIb Fondaparinux should not be used as the sole anticoagulant to support PCI in patients with NSTE-ACS due to an increased risk of catheter thrombosis. III: Harm

51 Dosing of Parenteral Anticoagulants During PCI Drug* Myocardial Revascularization In Patients Who Have Received Prior Anticoagulant Therapy Enoxaparin For prior treatment with enoxaparin, if last SC dose was administered 8 12 h earlier or if <2 therapeutic SC doses of enoxaparin have been administered, an IV dose of enoxaparin 0.3 mg/kg should be given If the last SC dose was administered within prior 8 h, no additional enoxaparin should be given ivalirudin For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusion For patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI In Patients Who Have Not Received Prior Anticoagulant Therapy 0.5 mg/kg 0.75 mg/kg IV loading dose 0.75 mg/kg loading dose, 1.75 mg/kg/h IV infusion

52 Dosing of Parenteral Anticoagulants During PCI Drug* Myocardial Revascularization In Patients Who Have Received Prior Anticoagulant Therapy Fondaparinux For prior treatment with fondaparinux, administer additional IV treatment with anticoagulant possessing anti-iia activity, considering whether GPI receptor antagonists have been administered In Patients Who Have Not Received Prior Anticoagulant Therapy N/A UFH IV GPI planned: additional UFH as needed (e.g., 2,000 5,000 U) to achieve ACT of s No IV GPI planned: additional UFH as needed (e.g., 2,000 5,000 U) to achieve ACT of s for HemoTec, s for Hemochron IV GPI planned: U/kg loading dose to achieve ACT of s No IV GPI planned: U/kg loading dose to achieve target ACT of s for HemoTec, s for Hemochron

53 Myocardial Revascularization Timing of Urgent CAG in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents Non enteric-coated aspirin (81 mg to 325 mg daily) should be administered preoperatively to patients I undergoing CAG. In patients referred for elective CAG, clopidogrel and ticagrelor should be discontinued for at least 5 days before surgery I and prasugrel for at least 7 days before surgery. In patients referred for urgent CAG, clopidogrel and ticagrelor should be discontinued for at least 24 hours to reduce major bleeding. I C

54 Myocardial Revascularization Timing of Urgent CAG in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents In patients referred for CAG, short-acting intravenous GP IIb/IIIa inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before surgery I and abciximab for at least 12 hours before to limit blood loss and transfusion. In patients referred for urgent CAG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontinued. IIb C

55 Special Patient Groups NSTE-ACS in Older Patients Older patients (**Those 75 years of age) with NSTE- ACS should be treated with GDMT, an early invasive I A strategy, and revascularization as appropriate. Pharmacotherapy in older patients with NSTE-ACS should be individualized and dose adjusted by weight and/or CrCl to reduce adverse events caused by agerelated changes in pharmacokinetics/dynamics, I A volume of distribution, comorbidities, drug interactions, and increased drug sensitivity. Management decisions for older patients with NSTE- ACS should be patient centered, considering patient preferences/goals, comorbidities, functional and cognitive status, and life expectancy. I

56 Special Patient Groups NSTE-ACS in Older Patients ivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older patients with NSTE-ACS, both initially and at PCI, given similar efficacy but less IIa bleeding risk. It is reasonable to choose CAG over PCI in older patients ** with NSTE-ACS who are appropriate candidates, particularly those with diabetes mellitus or complex 3-vessel CAD (e.g., SYNTAX score >22), with or without involvement of the proximal left anterior descending artery, to reduce cardiovascular disease events and readmission and to improve survival. IIa

57 Special Patient Groups Heart Failure and Cardiogenic Shock Patients with a history of HF and NSTE-ACS should be treated according to the same risk stratification guidelines and recommendations for patients without I HF. Selection of a specific revascularization strategy should be based on the degree, severity, and extent of CAD; associated cardiac lesions; the extent of LV I dysfunction; and the history of prior revascularization procedures. Early revascularization is recommended in suitable patients with cardiogenic shock due to cardiac pump failure after NSTE-ACS. I

58 Special Patient Groups Diabetes Mellitus Recommendation Class Level Medical treatment in the acute phase of NSTE-ACS and decisions to perform stress testing, angiography, and revascularization should be similar in patients with and without diabetes mellitus. I A

59 Special Patient Groups Post-CAG Recommendation Class Level Patients with prior CAG and NSTE-ACS should receive antiplatelet and anticoagulant therapy according to GDMT and should be strongly considered for early invasive strategy because of their increased risk. I

60 Special Patient Groups Perioperative NSTE-ACS Related to Noncardiac Surgery Patients who develop NSTE-ACS following noncardiac surgery should receive GDMT as recommended for patients in the general population but with the I C modifications imposed by the specific noncardiac surgical procedure and the severity of NSTE-ACS. In patients who develop NSTE-ACS after noncardiac surgery, management should be directed at the underlying cause. I C

61 Special Patient Groups Chronic Kidney Disease CrCl should be estimated in patients with NSTE-ACS, and doses of renally cleared medications should be adjusted according to the pharmacokinetic data for I specific medications. Patients undergoing coronary and LV angiography should receive adequate hydration. I C An invasive strategy is reasonable in patients with mild (stage 2) and moderate (stage 3) CKD. IIa

62 Special Patient Groups Women Women with NSTE-ACS should be managed with the same pharmacological therapy as that for men for acute care and for secondary prevention, with attention to weight and/or renallycalculated doses of antiplatelet and anticoagulant agents to reduce bleeding risk. I Women with NSTE-ACS and high-risk features (e.g., troponin positive) should undergo an early invasive strategy. I A Myocardial revascularization is reasonable in pregnant women with NSTE-ACS if an ischemia-guided strategy is ineffective for management of life-threatening complications. IIa C Women with NSTE-ACS and low-risk features (see Section in the full-text CPG) should not undergo early invasive treatment because of the lack of benefit and the possibility of harm. III: No enefit

63 Special Patient Groups Anemia, leeding, and Transfusion All patients with NSTE-ACS should be evaluated for the risk of bleeding. I C Anticoagulant and antiplatelet therapy should be weight-based where appropriate and should be adjusted when necessary for CKD to decrease the risk of bleeding in patients with NSTE-ACS. I A strategy of routine blood transfusion in III: No hemodynamically stable patients with NSTE-ACS and enefi hemoglobin levels greater than 8 g/dl is not t recommended.

64 Special Patient Groups Cocaine and Methamphetamine Users Patients with NSTE-ACS and a recent history of cocaine or methamphetamine use should be treated in the same manner as patients without cocaine- or methamphetaminerelated NSTE-ACS. The only exception is in patients with signs I C of acute intoxication (e.g., euphoria, tachycardia, and/or hypertension) and beta-blocker use, unless patients are receiving coronary vasodilator therapy. enzodiazepines alone or in combination with nitroglycerin are reasonable for management of hypertension and tachycardia in patients with NSTE-ACS and signs of acute cocaine or methamphetamine intoxication. IIa C eta blockers should not be administered to patients with ACS with a recent history of cocaine or methamphetamine use who demonstrate signs of acute intoxication due to the risk of potentiating coronary spasm. III: Harm C

65 Special Patient Groups Vasospastic (Prinzmetal) Angina CCs alone or in combination with long-acting nitrates are useful to treat and reduce the frequency of I vasospastic angina. Treatment with HMG-CoA reductase inhibitor, cessation of tobacco use, and additional atherosclerosis risk factor modification are useful in I patients with vasospastic angina. Coronary angiography (invasive or noninvasive) is recommended in patients with episodic chest pain accompanied by transient ST elevation to rule out severe obstructive CAD. I C

66 Special Patient Groups Vasospastic (Prinzmetal) Angina Provocative testing during invasive coronary angiography may be considered in patients with suspected vasospastic angina when clinical criteria and noninvasive testing fail to establish the diagnosis. IIb

67 Special Patient Groups ACS With Angiographically Normal Coronary Arteries Recommendation Class Level If coronary angiography reveals normal coronary arteries and endothelial dysfunction is suspected, invasive physiological assessment such as coronary flow reserve measurement may be considered. IIb

68 Special Patient Groups Stress (Takotsubo) Cardiomyopathy Stress (Takotsubo) cardiomyopathy should be considered in patients who present with apparent ACS I C and nonobstructive CAD at angiography. Imaging with ventriculography, echocardiography, or magnetic resonance imaging should be performed to confirm or exclude the diagnosis of stress (Takotsubo) I cardiomyopathy. Patients should be treated with conventional agents (ACE inhibitors, beta blockers, aspirin, and diuretics) as I C otherwise indicated if hemodynamically stable. Anticoagulation should be administered in patients who develop LV thrombi. I C

69 Special Patient Groups Stress (Takotsubo) Cardiomyopathy It is reasonable to use catecholamines for patients with symptomatic hypotension if outflow tract obstruction is IIa C not present. The use of an intra-aortic balloon pump is reasonable for patients with refractory shock. IIa C It is reasonable to use beta blockers and alphaadrenergic agents in patients with outflow tract IIa C obstruction. Prophylactic anticoagulation may be considered to inhibit the development of LV thrombi. IIb C

70 STEMI Management

71 STEMI Management Early Risk Assessment Onset of MI Reperfusion at a PCI-Capable Hospital Reperfusion at a Non PCI-Capable Hospital Delayed Invasive Management CAG in STEMI patients

72 Early Risk Assessment

73 Onset of MI Patient Related Delays and Initial Treatment Patient delay times are often longer in women, blacks, the elderly, and Medicaid-only recipients and are shorter for Medicare recipients (compared with privately insured patients) and patients who are taken directly to the hospital by emergency medical services (EMS) transport Mode of Transport to Hospital Patients with STEMI often do not call EMS or and are not transported to the hospital by ambulance. Patients with possible ischemic symptoms should be transported to the hospital by ambulance rather than by friends or relatives

74 Onset of MI Reperfusion Therapy for Patients with STEMI *Patients with cardiogenic shock or severe heart failure initially seen at a non PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: ). Angiography and revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.

75 Onset of MI Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals All communities should create and maintain a regional system of STEMI care that includes assessment and continuous quality improvement of EMS and hospitalbased activities. Performance can be facilitated by I participating in programs such as Mission: Lifeline and the D2 Alliance. Performance of a 12-lead ECG by EMS personnel at the site of FMC is recommended in patients with symptoms consistent with STEMI.. I

76 Onset of MI Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours. I A Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators. I A EMS transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI with an ideal FMC-to-device time system goal of 90 minutes or less. I

77 Onset of MI Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals Immediate transfer to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI who initially arrive at or are I transported to a non PCI-capable hospital, with an FMC-to-device time system goal of 120 minutes or less. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes because of unavoidable delays I

78 Onset of MI Regional Systems of STEMI Care, Reperfusion Therapy, and Time-to-Treatment Goals When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival. I Reperfusion therapy is reasonable for patients with STEMI and symptom onset within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia. Primary PCI is the preferred strategy in this population. IIa

79 Onset of MI Evaluation and Management of Patients With STEMI and Out-of- Hospital Cardiac Arrest Therapeutic hypothermia should be started as soon as possible in comatose patients with STEMI and out-ofhospital cardiac arrest caused by VF or pulseless VT, I including patients who undergo primary PCI. Immediate angiography and PCI when indicated should be performed in resuscitated out-of-hospital cardiac arrest patients whose initial ECG shows STEMI. I

80 Reperfusion at a PCI- Capable Hospital Primary PCI in STEMI Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours duration. I A Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours duration who have contraindications to fibrinolytic therapy, I irrespective of the time delay from FMC. Primary PCI should be performed in patients with STEMI and cardiogenic shock or acute severe HF, irrespective of time delay from MI onset. I

81 Reperfusion at a PCI- Capable Hospital Primary PCI in STEMI Primary PCI is reasonable in patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia IIa between 12 and 24 hours after symptom onset. PCI of a noninfarct artery may be considered in selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure. IIb

82 Reperfusion at a PCI- Capable Hospital Aspiration Thrombectomy The usefulness of selective and bailout aspiration thrombectomy in patients undergoing primary PCI is not well established.. IIb C Routine aspiration thrombectomy before primary PCI is not useful III A

83 Reperfusion at a PCI- Capable Hospital Use of Stents in Patients With STEMI Placement of a stent (MS or DES) is useful in primary PCI for patients with STEMI. I A MS* should be used in patients with high bleeding risk, inability to comply with 1 year of DAPT, or anticipated invasive or surgical procedures in the next year. DES should not be used in primary PCI for patients with STEMI who are unable to tolerate or comply with a prolonged course of DAPT because of the increased risk of stent thrombosis with premature discontinuation of one or both agents. I III C *alloon angioplasty without stent placement may be used in selected patients.

84 Reperfusion at a PCI- Capable Hospital Adjunctive Antithrombotic Therapy for Primary PCI Aspirin 162 to 325 mg should be given before primary PCI. I After PCI, aspirin should be continued indefinitely I A A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI. Options include Clopidogrel 600 mg Prasugrel 60 mg Ticagrelor 180 mg P2Y12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (MS or DES) during primary PCI using the following maintenance doses: I Clopidogrel 75 mg daily I Prasugrel 10 mg daily Ticagrelor 90 mg twice a day.

85 Reperfusion at a PCI- Capable Hospital Adjunctive Antithrombotic Therapy for Primary PCI It is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses after primary PCI It is reasonable to begin treatment with an intravenous GP IIb/IIIa receptor antagonist such as abciximab IIa A High-bolus-dose tirofiban Doublebolus eptifibatide at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving unfractionated heparin(ufh). IIa

86 Reperfusion at a PCI- Capable Hospital Adjunctive Antithrombotic Therapy for Primary PCI It may be reasonable to administer intravenous GP IIb/IIIa receptor antagonist in the precatheterization laboratory setting (eg, ambulance, ED) to patients with STEMI for whom primary PCI is intended It may be reasonable to administer intracoronary abciximab to patients with STEMI undergoing primary PCI. Continuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES placement. IIb IIb IIb C Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic attack. III

87 Reperfusion at a PCI- Capable Hospital Anticoagulant Therapy to Support Primary PCI UFH, with additional boluses administered as needed to maintain therapeutic activated clotting time levels, taking into account whether a GP IIb/IIIa receptor antagonist has been administered; I C ivalirudin with or without prior treatment with UFH. I In patients with STEMI undergoing PCI who are at high risk of bleeding, it is reasonable to use bivalirudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor IIa antagonist. Fondaparinux should not be used as the sole anticoagulant to support primary PCI because of the risk of catheter thrombosis III

88 Reperfusion at a Non-PCI- Capable Hospital

89 Reperfusion at a Non-PCI- Capable Hospital Fibrinolytic Therapy When There Is an Anticipated Delay to Performing Primary PCI Within 120 Minutes of FMC In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of FMC. In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability. Fibrinolytic therapy should not be administered to patients with ST depression except when a true posterior (inferobasal) MI is suspected or when associated with ST elevation in lead avr I IIa III A C

90 Reperfusion at a Non-PCI- Capable Hospital Adjunctive Antithrombotic Therapy With Fibrinolysis Aspirin (162- to 325-mg loading dose) and clopidogrel (300-mg loading dose for patients 75 years of age, 75-mg dose for patients >75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy. I A Aspirin should be continued. and clopidogrel (75 mg daily)should be continued for at least 14 days and up to 1 year in patients with STEMI who receive fibrinolytic therapy. It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy I IIa A A C

91 Reperfusion at a Non-PCI- Capable Hospital Adjunctive Anticoagulant Therapy With Fibrinolysis Patients with STEMI undergoing reperfusion with fibrinolytic therapy should receive anticoagulant therapy for a minimum of 48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization if performed. Recommended regimens include: A a.ufh administered as a weight-adjusted intravenous bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control, for 48 hours or until revascularization; b.enoxaparin administered according to age, weight, and creatinine clearance, given as an intravenous bolus, followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization, up to 8 days or until revascularization; or c.fondaparinux administered with initial intravenous dose, followed in 24 hours by daily subcutaneous injections if the estimated creatinine clearance is greater than 30 ml/min, for the duration of the index hospitalization, up to 8 days or until revascularization I C A

92 Reperfusion at a Non-PCI- Capable Hospital Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy Immediate transfer to a PCI-capable hospital for coronary angiography is recommended for suitable patients with STEMI who develop cardiogenic shock or acute severe HF, irrespective of the time delay from MI onset Urgent transfer to a PCI-capable hospital for coronary angiography is reasonable for patients with STEMI who demonstrate evidence of failed reperfusion or reocclusion after fibrinolytic therapy Transfer to a PCI-capable hospital for coronary angiography is reasonable for patients with STEMI who have received fibrinolytic therapy even when hemodynamically stable and with clinical evidence of successful reperfusion. Angiography can be performed as soon as logistically feasible at the receiving hospital, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy I IIa IIa

93 Delayed Invasive Management Coronary Angiography in Patients Who Initially Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion Cardiac catheterization and coronary angiography with intent to perform revascularization should be performed after STEMI in patients with any of the following: Cardiogenic shock or acute severe HF that develops after initial presentation; Intermediate- or high-risk findings on predischarge noninvasive ischemia testing; or I Myocardial ischemia that is spontaneous or provoked by minimal exertion during hospitalization. C

94 Delayed Invasive Management Coronary Angiography in Patients Who Initially Were Managed With Fibrinolytic Recommendations Therapy or Who Did Not Receive Reperfusion Class Level Coronary angiography with intent to perform revascularization is reasonable for patients with evidence of failed reperfusion or reocclusion after fibrinolytic therapy. Angiography can be performed as soon as logistically feasible. Coronary angiography is reasonable before hospital discharge in stable* patients with STEMI after successful fibrinolytic therapy. Angiography can be performed as soon as logistically feasible, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy. IIa IIa

95 Delayed Invasive Management PCI of an Infarct Artery in Patients Who Initially Were Managed With Fibrinolysis or Who Did Not Receive Reperfusion Therapy PCI of an anatomically significant stenosis in the infarct artery should be performed in patients with suitable anatomy and any of the following: Cardiogenic shock or acute severe HF; Intermediate- or high-risk findings on predischarge noninvasive ischemia testing; or Myocardial ischemia that is spontaneous or provoked by minimal exertion during hospitalization I C C Delayed PCI is reasonable in patients with STEMI and evidence of failed reperfusion or reocclusion after fibrinolytic therapy. PCI can be performed as soon as logistically feasible at the receiving hospital. IIa

96 Delayed Invasive Management PCI of an Infarct Artery in Patients Who Initially Were Managed With Fibrinolysis or Who Did Not Receive Reperfusion Therapy Delayed PCI of a significant stenosis in a patent infarct artery is reasonable in stable* patients with STEMI after fibrinolytic therapy. PCI can be performed as soon as logistically feasible at the receiving hospital, and ideally within 24 IIa hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy. Delayed PCI of a significant stenosis in a patent infarct artery greater than 24 hours after STEMI may be considered as part of an invasive strategy in stable* patients IIa Delayed PCI of a totally occluded infarct artery greater than 24 hours after STEMI should not be performed in asymptomatic patients with 1- or 2-vessel disease if they are hemodynamically and electrically stable and do not have evidence of severe ischemia. III