High risk non st segment elevation acute coronary syndrome

Definition

Table of Contents Show

• General Principles
• Epidemiology
• Etiology and Pathophysiology
• Clinical Presentation
• Physical Examination
• Diagnostic Testing
• Electrocardiography
• Laboratories
• Medications
• Revascularization
• Monitoring/Follow-Up
• What is high risk non ST
• What is a high risk NSTEMI?
• What is treatment for ACS without ST elevation?
• What are the 3 types of acute coronary syndrome?

• NSTEMI and UA are closely related conditions whose pathogenesis and clinical presentations are similar but differ in severity.
• If coronary flow is not severe enough or the occlusion does not persist long enough to cause myocardial necrosis (as indicated by positive cardiac biomarkers), the syndrome is labeled UA.
• NSTEMI is defined by an elevation of cardiac biomarkers and the absence of ST-segment elevation on the ECG.
• NSTEMI, like STEMI, can lead to cardiogenic shock.
• AHA/ACC guidelines provide a more thorough overview of NSTEMI/UA.1

Epidemiology

• The annual incidence of acute coronary syndrome (ACS) is >780,000 events, with 70% being NSTEMI/UA.
• Among patients with ACS, approximately 60% have UA and 40% have MI (one-third of MIs present with an acute STEMI).
• At 1 year, patients with UA/NSTEMI are at considerable risk for death (∼6%), recurrent MI (∼11%), and need for revascularization (∼50%–60%). It is important to note that although the short-term mortality of STEMI is greater than that of NSTEMI, the long-term mortality is similar.1
• Patients with NSTEMI/UA tend to have more comorbidities, both cardiac and noncardiac, than STEMI patients.
• Women with NSTEMI/UA have worse short-term and long-term outcomes and more complications compared to men. Much of this has been attributed to delays in recognition of symptoms and underutilization of guideline-directed medical therapy and invasive management.2

Etiology and Pathophysiology

• Myocardial ischemia results from decreased myocardial oxygen supply and/or increased demand. In the majority of cases, NSTEMI is due to a sudden decrease in blood supply via partial occlusion of the affected vessel. In some cases, markedly increased myocardial oxygen demand may lead to NSTEMI (demand ischemia), as seen in severe anemia, hypertensive crisis, acute decompensated HF, surgery, or any other significant physiologic stressor.
• UA/NSTEMI most often represents severe coronary artery narrowing or acute atherosclerotic plaque rupture/erosion and superimposed thrombus formation. Alternatively, it may also be due to progressive mechanical obstruction from advancing atherosclerotic disease, in-stent restenosis, or bypass graft disease.
• Plaque rupture may be triggered by local and/or systemic inflammation as well as shear stress. Rupture allows exposure of lipid-rich subendothelial components to circulating platelets and inflammatory cells, serving as a potent substrate for thrombus formation. A thin fibrous cap (thin-cap fibroatheroma) is felt to be more vulnerable to rupture and is most frequently represented as only moderate stenosis on angiography.
• Less common causes include dynamic obstruction of the coronary artery due to vasospasm (Prinzmetal angina, cocaine), coronary artery dissection (more common in women), coronary vasculitis, and embolus.

Clinical Presentation

Diagnostic Testing

Medications

• Patients presenting with UA/NSTEMI should receive medications that reduce myocardial ischemia through reduction in myocardial oxygen demand, improvement in coronary perfusion, and prevention of further thrombus formation.
• This approach should include antiplatelet, anticoagulant, and antianginal medications.
• Supplemental oxygen should be provided if the patient is hypoxemic (<90%) or having difficulty in breathing. Routine use of oxygen is not needed and possibly harmful.10,11
• Antiplatelet therapy
  • Table 4-13 summarizes available agents and dosing recommendations for use in ACS.

    Table 4-13: Antiplatelet Agents in UA/NSTEMI

    aInfusion doses should be decreased by 50% in patients with a GFR <30 mL/min and avoided in patients on HD.

    bAbciximab may be used in patients with ESRD because it is not cleared by the kidney.

    ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CVA, cerebrovascular accident; ESRD, end-stage renal disease; FDA, the Food and Drug Administration; GFR, glomerular filtration rate; HD, hemodialysis; MI, myocardial infarction; NSTEMI, non–ST-segment elevation myocardial infarction; UA, unstable angina.

  • Early dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor is strongly recommended for patients with NSTEMI/UA without a contraindication (e.g., uncontrolled severe bleeding, recent neuraxial surgery or trauma, recent hemorrhagic stroke, or intra-cranial or spinal metastases).
  • DAPT should ideally be continued for 12 months from the index ACS event, regardless of whether revascularization is performed or not. See the 2016 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease for specific recommendations tailored to stent type, bleeding risk, and other considerations.18
  • Aspirin blocks platelet aggregation within minutes.
    • A chewable 162–325-mg dose of ASA should be administered immediately at symptom onset or at first medical contact, unless a contraindication exists. This should be followed by ASA 81 mg daily indefinitely.
    • If an ASA allergy is present, clopidogrel may be substituted. An allergy consultation should be obtained for possible desensitization, preferably before the need for a coronary stent.
    • After PCI, ASA 81 mg is the current recommended dose in the setting of DAPT.
  • Clopidogrel is a prodrug whose metabolite blocks the P2Y12 receptor and inhibits platelet activation and aggregation by blocking the adenosine diphosphate receptor site on platelets.
    • The addition of clopidogrel to ASA reduced cardiovascular mortality and recurrent MI both acutely and at 11 months of follow-up.12
    • A loading dose of 600 mg should always be given in naïve patients.
    • In patients unable to take oral medications or unable to absorb oral medications because of ileus, rectal administration is unproven but has been reported. Alternatively, parenteral agents (e.g., cangrelor or eptifibatide), may be considered.
    • It can be used as part of the protocol in both the ischemia-driven and routinely invasive strategies.
  • Prasugrel is also a prodrug that blocks the P2Y12 adenosine receptor; its conversion to its active metabolite occurs faster and to a greater extent than clopidogrel.
    • It results in faster, greater, and more uniform platelet inhibition compared to clopidogrel at the expense of higher risk of bleeding.14
    • It decreases risk of CVD death, MI, CVA, and acute stent thrombosis as compared to clopidogrel in ACS patients, including STEMI patients.
    • It should be used with caution or avoided in patients older than 75 years and who weigh less than 60 kg. It is contraindicated in those with prior stroke or transient ischemic attack.
    • It is used only in the invasive approach of ACS and only after coronary anatomy is known and PCI is planned. There is no benefit over clopidogrel when tested before the initiation of PCI.
  • Ticagrelor is not a prodrug and blocks the P2Y12 adenosine receptor directly.
    • It reduces the risk of death, MI, CVA, and stent thrombosis as compared to clopidogrel in ACS patients, including STEMI patients.13
    • After the loading dose of ASA, the maintenance dose of ASA must be <100 mg.
    • It can be used as part of the protocol in both the ischemia-driven and early invasive strategies.
    • Barring any contraindication, ticagrelor is the preferred P2Y12 inhibitor of choice because of the mortality advantage over medications in this class.
    • The relative contraindications include baseline bradycardia, severe reactive airways disease, and prior hemorrhagic stroke.
  • Cangrelor is a parenteral, direct, and reversible inhibitor of the P2Y12 adenosine receptor.
    • It has a uniquely rapid onset (<2 minutes), potency (>90% platelet inhibition), and short duration of action after cessation (normal platelet function after 1 hour).
    • It reduces the risk of death, MI, urgent revascularization, or stent thrombosis among patients undergoing PCI.19
    • The FDA approved it only for patients undergoing PCI and is currently very expensive. Thus, it is not yet recommended for routine use in either ischemia-guided or invasive strategy. Thus, we recommend consulting a cardiologist before the use of cangrelor.
    • It is sometimes used as a bridging strategy in patients who have had recent PCI and require surgery where DAPT is prohibited. This approach is of unproven benefit.
  • Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists (abciximab, eptifibatide, or tirofiban) block the interaction between platelets and fibrinogen, thus targeting the final common pathway for platelet aggregation.
    • GPIIb/IIIa inhibitors play a limited role in ACS management with the introduction of more potent oral antiplatelet agents.
    • The routine use of GPIIb/IIIa antagonists on initial presentation, before angiography, in patients undergoing the invasive approach should be avoided because of increased risk of major bleeding and a lack of improvement in outcomes.
    • GPIIb/IIIa agents may be considered in scenarios of worsening ischemia despite DAPT, complex PCI, or bridging strategy in patients with an indication for DAPT (e.g., recent PCI) but require surgery.
    • Thrombocytopenia, which can be severe, is an uncommon complication of these agents and should prompt discontinuation.
  • Other concerns with antiplatelet agents
    • Timing of CABG
      • Owing to the increased risk of bleeding, it is currently recommended that clopidogrel be withheld for at least 5 days before CABG, prasugrel 7 days prior, ticagrelor 5 days prior, and cangrelor 1–6 hours prior.
      • Cangrelor or GPIIb/IIIa antagonists can be used as an alternative to clopidogrel, ticagrelor, and prasugrel in appropriate patients with UA/NSTEMI who are known to require surgical revascularization.
      • In general, DAPT should not be withheld during the initial management of ACS (i.e., before angiography) out of concern for the potential need for surgical revascularization. There is a larger risk of withholding beneficial therapy to patients in this setting than causing harm by delaying surgical revascularization.
    • Proton pump inhibitors (PPIs)
      • PPIs should be used in patients on DAPT with a prior history of gastrointestinal bleeding or increased risk of bleeding (e.g., elderly, known ulcers or Helicobacter pylori infection, or coprescribed warfarin, steroids, or NSAIDs).20
      • Pharmacologic studies have raised concerns about the potential of PPIs to blunt the efficacy of clopidogrel. However, in a prospective randomized trial, no apparent cardiovascular interaction was noted between PPIs and clopidogrel.19
    • Triple Therapy
      • Many patients requiring DAPT after PCI have a pre-existing indication for oral anticoagulation (OAC), such as atrial fibrillation or recent venous thromboembolism.
      • The use of DAPT and OAC (triple therapy) leads to higher bleeding risk, but recent trials suggest that triple therapy may not significantly reduce ischemic events any more than single antiplatelet therapy (SAPT; e.g., aspirin or clopidogrel) plus OAC.21,22
      • The most recent guidelines have not yet made specific recommendations, but they generally support tailoring selection of triple therapy (DAPT plus OAC) or SAPT plus OAC to the patient by comparing the risk of bleeding to the risk of ischemic events.18
      • In patients with an average risk of bleeding and average risk of ischemic events, we recommend triple therapy (e.g., aspirin, clopidogrel, and warfarin) for 4 weeks followed by SAPT plus OAC (e.g., clopidogrel and warfarin) for at least 1 year.
      • In patients with either high risk of bleeding or high risk of ischemic events, we recommend consultation with a cardiologist to tailor therapy.
• Anticoagulant therapy
  • See Table 4-14 for recommended use and dosing in ACS.

    Table 4-14: Anticoagulant Medications

    aLMWH should be given at reduced dose (50%) in patients with a serum creatinine >2 mg/dL or GFR <30 mL/min.

    bBivalirudin requires dosage adjustment in patients with a GFR less than 30 mL/min or those on hemodialysis.

    aPTT, activated partial thromboplastin time; ASA, aspirin; GFR, glomerular filtration rate; GP, glycoprotein; LMWH, low–molecular-weight heparin; MI, myocardial infarction; UFH, unfractionated heparin.

  • Anticoagulation accompanied by DAPT is required for all UA/NSTEMI patients, whether along the early invasive or conservative pathway.
  • Unfractionated heparin (UFH) works by binding antithrombin III, which catalyzes the inactivation of thrombin and other clotting factors.
    • Most commonly used and easily monitored but also most inconsistent in its anticoagulation and metabolism.
    • Heparin-induced thrombocytopenia (HIT) is a concern with prior use.
    • Easily reversed in the event of a severe hemorrhagic complication.
    • Always requires aggressive bolus dosing and anticoagulation monitoring in the setting of ACS.
    • Is a recommended anticoagulant to be used in the setting of ACS.
  • Low–molecular-weight heparin (LMWH) inhibits mostly factor Xa but also affects thrombin activity and offers an ease of administration (weight-based, twice-daily subcutaneous dose). The risk of HIT is lower but not absent.
    • As compared to UFH, LMWH has a more predictable anticoagulant effect.
    • It has a similar efficacy as UFH but is associated with a higher risk of postprocedural bleeding.25
    • LMWH must be adjusted for renal dysfunction and should be avoided in patients with severe impairments.
    • Enoxaparin 0.3 mg/kg IV should be administered at the time of PCI in patients who have received less than two therapeutic doses or if the last dose was received more than 8 hours before PCI.
  • Fondaparinux is a synthetic polysaccharide that selectively inhibits factor Xa and can be subcutaneously administered on a daily routine.
    • It is associated with an increased risk of thrombosis during PCI and should not be used without additional antithrombin anticoagulation; as such, it is not recommended for the routine management of ACS.
    • In patients not undergoing invasive management, fondaparinux may significantly reduce bleeding and improve outcomes compared to LMWH.28
  • Bivalirudin is a direct thrombin inhibitor given as a continuous IV infusion and requires partial thromboplastin time (PTT) monitoring when used for >4 hours.
    • It does not cause HIT and is used in the treatment of patients who develop HIT or patients with ACS who have history of HIT.
    • Bivalirudin can be given in conjunction with ASA and clopidogrel in patients presenting with UA/NSTEMI who will undergo a routine invasive strategy.
    • Bivalirudin alone compared to UFH/LMWH + GPIIb/IIIa inhibitor was associated with less bleeding.27
    • Recent evidence has shown that in ACS without significant GPIIb/IIIa inhibitor use, bivalirudin is associated with increased risk of stent thrombosis and target lesion revascularization.29
    • Caution should be taken with routine use of bivalirudin in ACS unless there is a high risk of bleeding.
• Anti-ischemic therapy (please also refer to Treatment section of stable angina)
  • Nitroglycerin
    • Treatment can be initiated at the time of presentation with sublingual nitroglycerin. NOTE: 40% of patients with chest pain not due to CAD will get relief with nitroglycerin (see Table 4-10).30
    • Patients with ongoing ischemic symptoms or those who require additional agents to control significant hypertension can be treated with IV nitroglycerin until pain relief, hypertension control, or both are achieved.
    • Rule out right ventricular (RV) infarct before administration of nitrates because this can precipitate profound hypotension.
  • β-Adrenergic blockers (BBs) (please also refer to the Treatment section for stable angina)
    • Oral therapy should be started early in the absence of contraindications.
    • Treatment with an IV preparation should be reserved for treatment of arrhythmia, ongoing chest pain, or advanced hypertension rather than routine use.
    • Routine use of IV BBs is associated with increased risk of cardiogenic shock and should be avoided.
    • Contraindications to BB therapy include advanced AV block, active bronchospasm, decompensated HF, cardiogenic shock, hypotension, and bradycardia.
  • Morphine 2–4 mg IV may be used as an adjunct to BB, nitrates, and calcium channel blockers. Care must be taken on not to mask further clinical evaluation by heavy use of narcotic medications.
• Adjunctive medical therapy
  • ACE inhibitors (refer to Treatment section for stable angina) are effective antihypertensive agents and have been shown to reduce mortality in patients with CAD and LV systolic dysfunction. ACE inhibitors should be used in patients with LV dysfunction (EF <40%), hypertension, or diabetes presenting with ACS. ARBs are appropriate in patients who cannot tolerate ACEIs.
  • Aldosterone antagonists should be added, if there are no contraindications (potassium >5 mEq/L or creatinine clearance [CrCl] <30 mL/min), after initiation of ACE inhibitors in patients with diabetes or an LVEF <40%.
  • 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors (statins) are potent lipid-lowering agents that reduce the incidence of ischemia, MI, and death in patients with CAD. High-intensity statins should be routinely administered within 24 hours of presentation in patients presenting with ACS. A lipid profile should be obtained in all patients.
    • Statin therapy reduces adverse outcomes through lipid lowering and potentially through pleiotropic effects (anti-inflammatory/atherosclerotic plaque–stabilizing effects).
    • Aggressive statin therapy reduces the risk of recurrent ischemia, MI, and death in patients presenting with ACS.31
    • A reduction in adverse CVD outcomes following early initiation of a high-dose statin with achievement of an LDL <70 mg/dL can be seen as early as 30 days following initial presentation with ACS.32 Aggressive LDL lowering also reduces the incidence of periprocedural MI following PCI.33
    • Patients who cannot achieve LDL <70 mg/dL after the use of a high-intensity statin should be evaluated for adjunctive PCSK9 inhibitors or ezetimibe.34,35 (Please refer to “Treatment” section for stable angina)
  • NSAIDs are associated with an increased risk of death, MI, myocardial rupture, hypertension, and HF in large meta-analyses.36 Adverse outcomes have been observed for both nonselective and cyclooxygenase-2 (COX-2) selective agents. NSAIDs should be discontinued in patients presenting with UA/NSTEMI.
  • Blood glucose should not be tightly controlled in diabetic patients who have suffered ACS because it may increase mortality. Goal is <180 mg/dL while avoiding hypoglycemia at all costs.

Revascularization

• PCI
  • Please see “Revascularization” section under Stable Angina for invasive management strategies.
• CABG
  • The indications for PCI versus CABG in patients with UA/NSTEMI are similar to those for individuals with chronic stable angina (please see section on “Revascularization” under Stable Angina).
  • The urgency of revascularization should weigh heavily in the decision for CABG; patients in cardiogenic shock may benefit from PCI and mechanical support compared to emergency cardiac surgery.
  • NSTEMI in the setting of critical left main CAD should prompt urgent surgical revascularization and consideration of intra-aortic balloon pump (IABP) for stabilization before the induction of anesthesia.