AUTHORS: George H. Nasr, MD and Pranav M. Patel, MD, FACC, FAHA, FSCAI
Acute coronary syndrome (ACS) represents a spectrum of clinical disorders that results from a sudden and unpredictable decrease of blood flow to the myocardium. ACS is a life-threatening disorder that incurs high, and in some cases immediate, mortality. This syndrome is usually due to interaction of vulnerable atherosclerotic plaque in the coronary arteries with that of activated clotting factors and platelets in the systemic circulation. In the modern era, management of ACS involves highly protocolized and systematic care of both procedural and medical therapies guided toward restoring blood flow to the heart. The spectrum of ACS is predominated by two important subtypes: ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). The third category of ACS is called unstable angina (UA) and falls within the NSTEMI subtype. The type of ACS dictates the timing of reperfusion, with STEMI being the most severe and always emergent. In this spectrum, UA and NSTEMI are represented by an abnormal ECG without the presence of ST-segment elevation in the appropriate clinical setting (i.e., chest discomfort). NSTEMI is additionally characterized by positive cardiac biomarkers. STEMI is characterized by ST-segment elevation on ECG in the appropriate clinical setting.1 With the advent and widespread use of the high-sensitivity troponin, the diagnosis of UA has changed to NSTEMI in almost all patients formerly diagnosed with UA. This is in part due to patients previously diagnosed with UA having abnormally elevated high-sensitivity troponin levels.2 Thus ACS should be thought of as a continuous spectrum as UA will often progress to a myocardial infarction (MI) if left untreated (Table 1). Because of this continuum, the 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines have grouped UA and NSTEMI into a single category called non-ST-elevation ACS (NSTE-ACS).3
TABLE 1 Acute Coronary Syndromes
Spectrum of Acute Coronary Syndrome | |||
---|---|---|---|
Unstable Angina | NSTEMI | STEMI | |
Chest discomfort | 1 | 1 | 1 |
Cardiac biomarkers | 2 | 1 | 1 |
ECG changes | TWI and/or ST depression | TWI and/or ST depression | ST elevation or presumed new left bundle branch block |
Pathophysiology | Partial/transient thrombotic occlusion | Partial/transient thrombotic occlusion | Complete thrombotic occlusion |
ECG, Electrocardiogram; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment myocardial infarction; TWI, T-wave inversion.
|
In the U.S., cardiovascular disease accounts for approximately 640,000 deaths each year. The estimated annual incidence of heart attacks in the U.S. is 600,000 new attacks and 200,000 recurrent attacks.4 Approximately 70% of MIs are listed as NSTEMI, with the remainder being listed as STEMI. Patients presenting with NSTE-ACS have worse long-term prognosis than patients presenting with STEMI. This is due to the higher comorbidity profile of patients presenting with NSTE-ACS (i.e., significantly older population, higher burden of comorbidities, and frequent history of coronary artery disease [CAD]). The underlying etiology, atherosclerotic CAD, remains the number one cause of mortality.4
In the U.S., the median age at ACS presentation is 68 yr old (interquartile range 56 to 79), and the male:female ratio is approximately 3:2. In a 2005 to 2011 study sponsored by National Heart, Lung, and Blood Institute, the average age-adjusted first MI or fatal coronary heart disease rates per 1000 population in patients age 35 to 84 yr of age were 3.7 for white men, 5.9 for black men, 2.1 for white women, and 4.0 for black women.4 As noted in this study, heart disease affects African Americans disproportionately. Heart disease is also the leading cause of death in women, surpassing all forms of cancer.4
Hypertension, diabetes mellitus, dyslipidemia, tobacco use, and family history of premature CAD (CAD in a male first-degree relative younger than 55 yr or a female younger than 65 yr of age) are all associated risk factors for CAD. There are also female-specific risk factors for CAD, including disorders of pregnancy and early onset of menopause. Refer to the topic Angina Pectoris for an extensive list of risk factors. Presence of these risk factors cause damage to the vascular endothelium and progression of atherosclerotic coronary artery plaques.
TABLE 2 Grading of Angina Pectoris According to CCS Classification
Class | Description of Stage | ||
---|---|---|---|
I | Ordinary physical activity does not cause angina, such as walking or climbing stairs. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. | ||
II | Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly; walking uphill; walking or stair climbing after meals; in cold, in wind, or under emotional stress; or only during the few hours after awakening. Angina occurs on walking 0.2 blocks on the level and climbing 0.1 flight of ordinary stairs at a normal pace and under normal conditions. | ||
III | Marked limitations of ordinary physical activity. Angina occurs on walking 1-2 blocks on the level and climbing one flight of stairs under normal conditions and at a normal pace. | ||
IV | Inability to carry on any physical activity without discomfort-anginal symptoms may be present at rest. |
Adapted with permission from Campeau L: Grading of angina pectoris (letter), Circulation 54:522-523, 1976. © 1976, American Heart Association, Inc.From Braunwald E et al: ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina), J Am Coll Cardiol 36:970-1062, 2000.
The hallmark of ACS is vulnerable atherosclerotic plaque, which typically has a thin fibrous cap and a large lipid core. This vulnerable plaque can spontaneously rupture, which leads to platelet activation and aggregation and a systemic inflammatory cascade, leading to thrombus formation. STEMI typically results from complete thrombotic occlusion of a coronary artery, whereas NSTE-ACS often has partial occlusion. Angiographically, it is often the intermediate coronary artery lesions (30% to 50% diameter vessel stenosis) that lead to subtotal or total vessel occlusion in two thirds of STEMI cases.
Chest pain mimicking ACS may be the result of various underlying disorders, some of which are also accompanied by ECG changes and/or cardiac biomarker release. Examples include acute pulmonary embolism, acute aortic dissection, pericarditis, myocarditis, costochondritis, pneumonia, tension pneumothorax, perforating ulcer, or esophageal perforation (i.e., Boerhaave syndrome). Refer to topics Angina Pectoris, Coronary Artery Syndrome, and Myocardial Infarction for extensive differential diagnoses of chest pain.
Focused history and physical examination, 12-lead ECG, cardiac biomarkers, and chest radiograph (CXR) are the cornerstone of initial chest pain workup. Initial biomarkers may not be positive early in the disease process. Conventional troponin levels are often drawn every 6 to 8 h for a total of three sets for the purposes of ruling out MI or until peak to determine the severity of an established MI, but with the advent of the high-sensitivity troponin, the time to rule in MI can be done in as little as 3 h from initial presentation.1 Echocardiogram may reveal new regional wall motion abnormalities or newly depressed left ventricular (LV) function or aneurysm formation. Fig. 1 summarizes the evaluation of patients for ACS.
Figure 1 Evaluation of patients for acute coronary syndrome (ACS).
CAD, Coronary artery disease; CP, chest pain; CRI, chronic renal insufficiency; ECG, electrocardiogram; ED, emergency department; h/o, history of; LBBB, left bundle branch block; NSTE, non-ST-segment elevation; NSTEMI, non-ST-segment elevation myocardial infarction; PCP, primary care physician; PVD, peripheral vascular disease; STE, ST-segment elevation; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina.
From Adams JG et al: Emergency medicine: clinical essentials, ed 2, Philadelphia, 2013, Elsevier.
Figure E2 Timing of release of cardiac biomarkers in acute coronary syndrome.
HTN, Hypertension; LBBB, left bundle branch block; MI, myocardial infarction; STE, ST elevation; ULN, upper limit of normal.
Modified from Shapiro BP, Jaffe AS: Cardiac biomarkers. In Murphy JG, Lloyd MA [eds]: Mayo Clinic cardiology: concise textbook, ed 3, Rochester, MN: Mayo Clinic Scientific Press and New York, 2007, Informa Healthcare USA, pp 773-780; and Anderson JL et al: J Am Coll Cardiol 50:e1-e157, 2007, Fig. 5.
Risk models and scores such as TIMI (see Risk Assessment in Myocardial Infarction topic), PURSUIT, HEART, and GRACE based on clinical, ECG, risk factors, and laboratory data at presentation help to discriminate patients at high risk versus low risk for short- and intermediate-term adverse outcomes (Fig. E2, C).6 These risk stratification models are helpful in determining the timing and strategy of treatment.
The overall goal for patients with ACS is to relieve myocardial ischemia and to prevent recurrent cardiovascular events. This is achieved by targeting both vulnerable coronary plaque and activated clotting factors and platelets in the blood. Revascularization, whether it is chemical (i.e., thrombolysis) or mechanical (i.e., percutaneous coronary intervention [PCI]), is needed to prevent further events and improve flow within the coronary artery lumen. In the modern era, PCI has improved outcomes for patients presenting with ACS.8 For patients with STEMI, time from onset of ischemia to revascularization guides the reperfusion strategy. STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 min of first medical contact (Figs. 3 and 4). At non-PCI-capable hospitals where the first medical contact to PCI is more than 120 min, thrombolytic therapy should be given to eligible patients within the first 12 h after symptom onset; thrombolytics should not be administered 24 h after initial diagnosis of STEMI (Table 3).8 In patients who receive thrombolytic agents, coronary angiography can be done at a receiving hospital as soon as possible but not within the first 2 to 3 h after administration of a fibrinolytic agent. Thrombolytic agents come in two forms, fibrin specific (alteplase, reteplase, tenecteplase, staphylokinase) and nonfibrin specific (streptokinase, anistreplase, urokinase). Absolute contraindications to thrombolytic therapy include the following: History of intracranial hemorrhage, known structural cerebral vascular lesion, known intracranial neoplasm, ischemic stroke within 3 mo, suspected aortic dissection, active bleeding, head trauma within 3 mo, or intracranial surgery within 2 mo. Relative contraindications include ischemic stroke more than 3 mo prior, dementia, major surgery within 3 wk, current oral anticoagulant therapy, and traumatic or prolonged CPR.9 Antithrombotic therapy is needed to reduce thrombus burden, prevent further thrombosis, and improve coronary artery flow.
TABLE 3 Reperfusion Strategies
Anticipated time from FMC to PCI | >120 min | <120 min |
and | or | |
Symptom duration? | <12 h | <24 h |
and | or | |
Thrombolytic eligible? | YES | NO |
Reperfusion strategy | Thrombolytics and transfer | Primary PCI |
FMC, First medical contact; PCI, percutaneous coronary intervention.
TABLE 10 Indications and Cautions for Adjunctive Medical Therapies for Patients With ST-Elevation Myocardial Infarction
Therapy | Indications | Cautions |
---|---|---|
Beta-adrenergic receptor-blocking agents | Oral: All patients without contraindication IV: Patients with refractory hypertension or ongoing ischemia without contraindication | Signs of congestive heart failure Low-output state Increased risk for cardiogenic shock Prolonged first-degree or high-grade atrioventricular block Reactive airways disease |
Angiotensin-converting enzyme (ACE) inhibitors | Anterior myocardial infarction and LVEF ≤0.40 or congestive heart failure All patients without contraindication | Hypotension Renal failure Hyperkalemia |
Angiotensin receptor-blocking agents (ARBs) | Intolerant of ACE inhibitors | Hypotension Renal failure Hyperkalemia |
Statins | All patients without contraindications | With drugs metabolized via CYP3A4, fibrates Monitor for myopathy, hepatotoxicity Adjust dose for lipid targets |
Nitroglycerin | Ongoing chest pain Hypertension and congestive heart failure | Suspected right ventricular infarction SBP <90 (or 30 mm Hg below baseline) Recent use of a type 5 PDE inhibitor |
Oxygen | Clinically significant hypoxemia (SpO2 <90) Congestive heart failure Dyspnea | Chronic obstructive pulmonary disease and CO2 retention |
Morphine | Pain Anxiety Pulmonary edema | Lethargic or moribund patient Hypotension Bradycardia Known hypersensitivity |
IV, Intravenous; LVEF, left ventricular ejection fraction; PDE, phosphodiesterase; SBP, systolic blood pressure.
From Zipes DP: Braunwalds heart disease: a textbook of cardiovascular medicine, ed 11, Philadelphia, 2019, Elsevier.
TABLE 9 Pharmacologic Characteristics of Parenteral Anticoagulants Commonly Used in the Management of Patients With Acute Coronary Syndrome
Unfractionated Heparin | Enoxaparin | Bivalirudin | Fondaparinux | |
---|---|---|---|---|
Route of administration | IV | SC (first dose IVa) | IV | SC (first dose IVa) |
Frequency of dosing | Continuous IV infusion | Twice daily; once daily if CrCl <30 ml/min | Continuous IV infusion | Once-daily injection |
Clearance | Primarily nonrenal | Renal | Renal, proteolytic cleavage | Renal |
Use in ACS patients with moderate renal impairment | Yes | Yes (dose reduction) | Yes (dose reduction) | Yesb |
Use in ACS patients undergoing dialysis | Yes | No experience | Yes (dose reduction) | No experiencec |
Routine laboratory monitoring | Yes | No | Nod | No |
Dose | Adjust dose according to the results of the aPTT | Fixed weight adjusted | Fixed weight adjusted | Fixed |
Accumulation in renal failure | No | Yes | Yes | Yes |
Nonanticoagulant side effects | Allergy, HIT | HIT (rare) | - | - |
Nonbleeding contraindications | Allergy, immune HIT | Allergy, immune HIT | Allergy | Allergy |
Antidote | Protamine sulfate | Protamine sulfate partially reverses | No | No |
ACS, Acute coronary syndromes; aPTT, activated partial thromboplastin time; CrCl, creatinine clearance; HIT, heparin-induced thrombocytopenia; IV, intravenous; SC, subcutaneous.
a The first dose of enoxaparin was given by the intravenous route in the TIMI-11B (Thrombolysis In Myocardial Infarction 11B) and EXTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment, Thrombolysis in Myocardial Infarction 25) studies. The first dose of fondaparinux was given by the intravenous route in the OASIS-6 (Optimal Antiplatelet Strategy for Interventions 6) trial.
b Acute coronary syndrome patients with creatinine up to 265 μmol/L were eligible for inclusion in the OASIS-5 and -6 trials (equivalent to an estimated creatinine clearance of 15-20 ml/min in a 70-kg patient who is 70 yr of age).
c Fondaparinux is contraindicated in patients with venous thromboembolism who have severe renal impairment.
d Monitoring and dose adjustment required in patients with creatinine clearance below 30 ml/min.
From Hoffman R et al: Hematology: basic principles and practice, ed 7, Philadelphia, 2018, Elsevier.
TABLE 8 Pharmacologic Characteristics of Intravenous Antiplatelet Drugs Used in the Management of Acute Coronary Syndrome
Characteristic | Gp Iib/Iiia Inhibitors | ADP RECEPTOR ANTAGONISTS | ||
---|---|---|---|---|
Abciximab | Eptifibatide | Tirofiban | Cangrelor | |
Class | Fab fragment | Nonpeptide | Cyclic heptapeptide | Nonthienopyridine |
Onset | Rapid | Rapid | Rapid | Rapid |
Drug half-life | 10-30 min | 2 h | 2.5 h | 3-6 min |
Reversibility of platelet inhibition | Slow | Rapid | Rapid | Rapid |
Excretion | Unknown | 40%-70% renal | 50% renal | Dephosphorylation |
ADP,Adenosine diphosphate; GP, glycoprotein.
From Hoffman R et al: Hematology: basic principles and practice, ed 7, Philadelphia, 2018, Elsevier.
TABLE 7 Pharmacologic Characteristics of Oral Antiplatelet Drugs Commonly Used in the Management of Acute Coronary Syndrome
Characteristic | Aspirin | ADP Receptor Antagonists | ||
---|---|---|---|---|
Clopidogrel | Prasugrel | Ticagrelor | ||
Class | COX inhibitor | Thienopyridine (second generation) | Thienopyridine (third generation) | Cyclopentyl triazolopyrimidine |
Target | COX-1 | P2Y12 | P2Y12 | P2Y12 |
Dose | 162- to 325-mg loading dose; 75-325 mg/day maintenance dose | 300- to 600-mg loading dose; 75 mg/day maintenance dose | 60-mg loading dose; 10 mg/day maintenance dose | 180-mg loading dose; 90 mg bid maintenance dose |
Prodrug | No | Yes | Yes | No |
Time to effecta | <1 h | 4-6 hb | <1 h | <1 h |
Drug half-life | 20 min | Min | Min | 12 hr |
Reversible | No | No | No | Yes |
ADP, Adenosine diphosphate; bid, twice daily; COX, cyclooxygenase.
b Increased antithrombotic benefit was seen after the first hour in patients enrolled in the COMMIT trial who did not receive a loading dose, but maximum effect is not seen until after 4-6 h.
From Hoffman R et al: Hematology: basic principles and practice, ed 7, Philadelphia, 2018, Elsevier.
TABLE 5 Summary of Recommendations for Antithrombotic Therapy
Recommendations | Dosing, Special Considerations | COR | LOE |
---|---|---|---|
Aspirin | |||
Nonenteric-coated aspirin to all patients promptly after presentation | 162-325 mg | I | A |
Aspirin maintenance dose continued indefinitely | 81-325 mg/day∗ | I | A |
P2Y12 Inhibitors | |||
Clopidogrel loading dose followed by daily maintenance dose in patients unable to take aspirin | 75 mg | I | B |
P2Y12 inhibitor, in addition to aspirin, for up to 12 mo for patients treated initially with either an early invasive or initial ischemia-guided strategy: | I | B | |
300- or 600-mg loading dose, then 75 mg/day | |||
180-mg loading dose, then 90 mg twice daily | |||
P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) continued for at least 12 mo in post-PCI patients treated with coronary stents | N/A | I | B |
Ticagrelor in preference to clopidogrel for patients treated with an early invasive or ischemia-guided strategy | N/A | IIa | B |
Glycoprotein (GP) IIb/IIIa Inhibitors | |||
GP IIb/IIIa inhibitor in patients treated with an early invasive strategy and DAPT with intermediate/high-risk features (e.g., positive troponin) | Preferred options are eptifibatide or tirofiban | IIb | B |
Parenteral Anticoagulant and Fibrinolytic Therapy | |||
SC enoxaparin for duration of hospitalization or until PCI is performed | 1 mg/kg SC every 12 h (reduce dose to 1 mg/kg/day SC in patients with CrCl <30 ml/min) Initial 30-mg IV loading dose in select patients | I | A |
Bivalirudin until diagnostic angiography or PCI is performed in patients with early invasive strategy only | Loading dose 0.10 mg/kg, followed by 0.25 mg/kg/h Only provisional use of GP IIb/IIIa inhibitor in patients also treated with DAPT | I | B |
SC fondaparinux for the duration of hospitalization or until PCI is performed | 2.5 mg/day SC | I | B |
Administer additional anticoagulant with antiIIa activity if PCI is performed while patient is on fondaparinux | N/A | I | B |
IV UFH for 48 hr or until PCI is performed | Initial loading dose 60 IU/kg (max 4000 IU) with initial infusion 12 IU/kg/h (max 1000 IU/h) Adjusted to therapeutic APTT range | I | B |
IV fibrinolytic treatment not recommended in patients with NSTE-ACS | N/A | III: Harm | A |
APTT, Activated partial thromboplastin time; COR, class of recommendation; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; IV, intravenous; LOE, level of evidence; max, maximum; N/A, not available; NSTE-ACS, non-ST-elevation acute coronary syndromes; PCI, percutaneous coronary intervention; SC, subcutaneous; UFH, unfractionated heparin.
∗The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg/day.
Modified from Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association task force on practice guidelines, J Am Coll Cardiol 64:e139-228, 2014, in Zipes DP: Braunwalds heart disease: a textbook of cardiovascular medicine, ed 11, Philadelphia, 2019, Elsevier.
TABLE 6 2014 Guideline Recommendations for Antithrombotic Agents in Patients With Non-ST-Elevation Acute Coronary Syndrome
Antiplatelet Therapy | |||
Nonenteric-coated, chewable aspirin (162-325 mg) should be given to all patients without contraindications on presentation, and a maintenance dose of aspirin (81-325 mg/day) continued indefinitely. In patients who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel (300 or 600 mg) followed by a daily maintenance dose of 75 mg should be substituted. Either clopidogrel or ticagrelor can be used initially with either an early invasive or ischemic guided strategy (COR I, LOE: B). Ticagrelor may be preferred over clopidogrel as the initial treatment (COR IIa, LOE: B). In patients treated with ticagrelor, the preferred aspirin maintenance dose is 81 mg/day. Use prasugrel only in patients receiving coronary stents (COR I, LOE: B). The use of glycoprotein IIb/IIIa receptor inhibitors is reserved mainly to the time of PCI in high-risk patients who were not adequately pretreated with P2Y12 inhibitors (COR I, LOE: A) or in those patients who were adequately pretreated with P2Y12 inhibitors but have a high-risk profile (COR IIa, LOE: B). Clopidogrel and ticagrelor should be discontinued at least 5 days (COR I, LOE: B) and prasugrel at least 7 days (COR I, LOE: C) before major surgery. | |||
Anticoagulant Therapy | |||
Enoxaparin is recommended at presentation (COR I, LOE: A); other options include unfractionated heparin (UFH) (COR I, B) and fondaparinux (COR I, LOE: B). If an early invasive strategy is planned, bivalirudin (COR I, LOE: B) is also an option. If fondaparinux is used initially, add UFH or bivalirudin just before or during PCI to prevent catheter-related thrombosis (COR I, LOE: B). Bivalirudin is preferred over UFH plus GP IIb/IIIa inhibitor in patients undergoing PCI who are at high risk of bleeding (COR IIa, LOE: B). It is reasonable to use enoxaparin during PCI if it was used as the initial anticoagulant (COR IIb, LOE: B). |
COR, Class of recommendation; LOE, level of evidence; PCI, percutaneous coronary intervention.
Modified from Eisen A, Giugliano RP: Antiplatelet and anticoagulation treatment in patients with non-ST-segment elevation acute coronary syndrome: comparison of the updated North American and European guidelines, Cardiol Rev 24:170-176, 2016; and Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 64: e139-228, 2014, in Zipes DP: Braunwalds heart disease: a textbook of cardiovascular medicine, ed 11, Philadelphia, 2019, Elsevier.
TABLE 4 Summary of Recommendations for Standard Medical Therapy in the Early Hospital Care Phase of Management of Patients With Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS)
Recommendations | COR | LOE |
---|---|---|
Oxygen | ||
Administer supplemental oxygen only with oxygen saturation <90%, respiratory distress, or other high-risk features for hypoxemia. | I | C |
Nitrates | ||
Administer sublingual NTG every 5 min ×3 for continuing ischemic pain and then assess need for IV NTG. | I | C |
Administer IV NTG for persistent ischemia, HF, or hypertension. | I | B |
Nitrates are contraindicated with recent use of a phosphodiesterase inhibitor. | III: Harm | B |
Analgesic Therapy | ||
IV morphine sulfate may be reasonable for continued ischemic chest pain despite maximally tolerated antiischemic medications. | IIb | B |
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 | B |
Beta-Adrenergic Blockers | ||
Initiate oral beta blockers within the first 24 h in the absence of HF, low-output state, risk for cardiogenic shock, or other contraindications to beta blockade. | I | A |
Use of sustained-release metoprolol succinate, carvedilol, or bisoprolol is recommended for beta-blocker therapy with concomitant NSTE-ACS, stabilized HF, and reduced systolic function. | I | C |
Reevaluate to determine subsequent eligibility in patients with initial contraindications to beta blockers. | I | C |
It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS. | IIa | C |
IV beta blockers are potentially harmful when risk factors for shock are present. | III: Harm | B |
Calcium Channel Blockers (CCBs) | ||
Administer initial therapy with nondihydropyridine CCBs with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval >0.24 sec, or second- or third-degree atrioventricular block without a cardiac pacemaker. | I | B |
Administer oral nondihydropyridine calcium antagonists with recurrent ischemia after use of beta blocker and nitrates in the absence of contraindications. | I | C |
CCBs are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effects.∗ | I | C |
Long-acting CCBs and nitrates are recommended for patients with coronary artery spasm. | I | C |
Immediate-release nifedipine is contraindicated in the absence of a beta-blocker. | III: Harm | B |
Cholesterol Management | ||
Initiate or continue high-intensity statin therapy in patients with no contraindications. | I | A |
Obtain a fasting lipid profile, preferably within 24 h. | IIa | C |
COR, Class of recommendation; HF, heart failure; IV, intravenous; LOE, level of evidence; LV, left ventricular; MACE, major adverse cardiovascular events; N/A, not available; NSAIDs, nonsteroidal antiinflammatory drugs; NTG, nitroglycerin.
∗Short-acting dihydropyridine calcium channel antagonists should be avoided.
From Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association task force on practice guidelines, J Am Coll Cardiol 64:e139-228, 2014 in Zipes DP: Braunwalds heart disease: a textbook of cardiovascular medicine, ed 11, Philadelphia, 2019, Elsevier.
TABLE 11 Strategies Aimed at Minimizing the Risk of Bleeding in Patients Treated With Triple Therapy (Dual Antiplatelet Therapy and an Oral Anticoagulant)
Proposed Approach | Rationale | ||
---|---|---|---|
Aspirin maintenance dose ≤100 mg/day | Higher aspirin maintenance doses increase bleeding, and there is no evidence that they improve efficacy. | ||
PPI with a preference for agents that interfere less with CYP 2C19 (e.g., pantoprazole) | Much of the excess bleeding is from the GI tract. The use of acid-suppressive agents that interfere less with CYP 2C19 minimizes the potential for a negative interaction with clopidogrel. | ||
Preference for a nonvitamin K antagonist oral anticoagulant | Dabigatran 110 mg twice daily and apixaban 2.5 or 5.0 mg twice daily are associated with lower rates of bleeding than warfarin. | ||
For warfarin, use a target INR of 2-2.5 | Some evidence that a restricted target INR range reduces the risk of bleeding. | ||
Manage warfarin in a specialized anticoagulation clinic | Compared with usual care, specialist clinics achieve a higher TTR of the INR. | ||
Minimize duration of triple therapy | The risk of bleeding is highest during the first 30 days but remains elevated with long-term treatment. | ||
Avoid NSAIDs | NSAIDs are a common cause of upper GI bleeding. | ||
Avoid prasugrel and ticagrelor | Prasugrel and ticagrelor cannot be recommended because they are more potent than clopidogrel and cause more bleeding. |
CYP, Cytochrome P-450; GI, gastrointestinal; INR, international normalized ratio; NSAID, nonsteroidal antiinflammatory drug; PPI, proton pump inhibitor; TTR, time in therapeutic range.
From Hoffman R et al: Hematology: basic principles and practice, ed 7, Philadelphia, 2018, Elsevier.
TABLE 12 Pharmacologic Characteristics of Warfarin and New Oral Anticoagulants Evaluated in Phase III Trials for the Long-Term Management of Acute Coronary Syndrome
Characteristic | Warfarin | Rivaroxaban | Apixaban |
---|---|---|---|
Target | VKORC1 | Factor Xa | Factor Xa |
Prodrug | No | No | No |
Bioavailability (%) | 100 | 80 | 60 |
Dosing | Variable, once daily | Fixed, 2.5 or 5 mg twice dailya | Fixed, 5 mg twice daily (2.5 mg twice daily in selected patients) |
Half-life | Mean: 40 h (range: 20-60 h) | 7-11 h | 12 h |
Renal clearance (%) | Nil | 66b | 25 |
Routine coagulation monitoring | Yes (INR) | No | No |
Drug interactions | Multiple | Potent inhibitors of CYP3A4 and P-gpc | Potent inhibitors of CYP3A4 and P-gpc |
Antidote | Yes (vitamin K, PCC, FFP) | Yes (Andexanet alfa) | Yes (Andexanet alfa) |
Approved for ACS management | Yes | Yes, in Europe | No |
ACS, Acute coronary syndromes; CYP3A4, cytochrome P-450 3A4; FFP, fresh frozen plasma; fXa, activated factor X; INR, international normalized ratio; PCC, prothrombin complex concentrates; P-gp, P-glycoprotein; VKORC1, C1 subunit of vitamin K epoxide reductase. Strategies Aimed at Minimizing the Risk of Bleeding in Patients Treated With Triple Therapy (Dual Antiplatelet Therapy and an Oral Anticoagulant).
a A once-daily regimen was tested in atrial fibrillation.
b Half of renally cleared rivaroxaban is cleared as unchanged drug and half as inactive metabolites.
c Potent inhibitors of both CYP3A4 and P-glycoprotein include azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) and protease inhibitors, such as ritonavir. Potent inhibitors of CYP3A4 include azole antifungals, macrolide antibiotics (e.g., clarithromycin), and protease inhibitors (e.g., atazanavir).
From Hoffman R et al: Hematology: basic principles and practice, ed 7, Philadelphia, 2018, Elsevier.
Acute Coronary Syndrome (Patient Information)
Angina Pectoris (Related Key Topic)
Coronary Artery Disease (Related Key Topic)
Myocardial Infarction (Related Key Topic)
Hypertension (Related Key Topic)