Approach

A 12-lead ECG should be obtained and interpreted within 10 minutes of initial presentation.[1][77]​​​ Until the results of cardiac biomarkers are known further management will be dictated by ECG findings of ST-elevation (see ST-elevation myocardial infarction [STEMI]), or a working diagnosis of non-ST-elevation acute coronary syndrome (NSTE-ACS) which would include both non-ST-elevation myocardial infarction (NSTEMI; classically ST-segment depression, with elevated cardiac biomarkers, see non-ST-elevation myocardial infarction) or UA (unstable angina; history and ECG changes suggestive of NSTEMI with normal cardiac biomarkers).

All patients should be given a single loading dose of aspirin as soon as possible, unless they have significant bleeding risk or hypersensitivity to aspirin. Pain relief with nitrates should be offered as soon as possible. Morphine can be added if nitrates are ineffective.[1][2]

Initial treatment

In cases where a cardiac etiology is suspected, early management interventions should be started while further results are still pending.[1]​ The aims of treatment in NSTE-ACS are to alleviate pain and anxiety and to prevent recurrence of ischemia in any patient with UA, and to modify risk factors for cardiovascular disease (CVD) and offer support for lifestyle changes.[2][106]

Monitoring

Patients with suspected UA should be triaged to high acuity and be immediately placed on cardiac monitoring with an available defibrillator.[1][2]​​ Patients should be monitored for 24-48 hours depending on symptomatology and angiographic findings. The duration of cardiac monitoring is generally dictated by the clinical condition, symptoms, presence of ischemia, and arrhythmias.In general, rhythm monitoring up to 24 hours or to percutaneous coronary intervention (PCI; whichever comes first) is recommended for patients at low risk for cardiac arrhythmias and for >24 hours is recommended in patients at increased risk for cardiac arrhythmias.[1]​ After PCI, the duration of cardiac monitoring depends on the presence or absence of ongoing ischemia, and hemodynamic or electrical instability. In general, after successful revascularization of all ischemic lesions, monitoring should be continued for 12-24 hours and in cases without revascularization, it should be continued for 24-48 hours.[107]

Risk assessment

The early estimation of risk is based on the Thrombolysis in Myocardial Infarction (TIMI) risk score and the Global Registry of Acute Coronary Events (GRACE) risk model.[2] [ Thrombolysis in Myocardial Infarction (TIMI) Score for Unstable Angina Non ST Elevation Myocardial Infarction Opens in new window ] ​​​​​ [ GRACE Score for Acute Coronary Syndrome Prognosis Opens in new window ] ​​​​​ The TIMI risk score and GRACE score both identify patients who would benefit from early invasive therapy, and use of these scores is recommended to guide the timing of coronary angiography.[93]​ See diagnosis section for more information on risk stratification.

In older patients, the presence of comorbid conditions, variable preexisting functional status and patient preferences regarding goals of care make disease management more complex. An individualized and patient-centered approach is recommended.[108]

Oxygen

Supplemental oxygen should be given to patients with NSTE-ACS with arterial saturation <90%, respiratory distress, or other high-risk features of hypoxemia.[2]

Pain relief

Pain relief with sublingual nitrates should be offered as soon as possible. Intravenous nitrates should be considered for all patients who continue to have chest pain. There are no large-scale randomized placebo-controlled trials of nitrate use in UA. However, in multiple small open-label studies, intravenous nitrates have been very useful for relief of angina and symptomatic relief.[109]​ The main contraindication for their use is hypotension. The major therapeutic benefit is related to the venodilator effects that lead to decrease in myocardial preload and left ventricular end diastolic volume, resulting in a decrease in myocardial oxygen consumption. Nitrates also dilate coronary vessels and improve collateral flow. The dose should be titrated up until desired effects are achieved or adverse effects, notably headache or hypotension, develop. Following stabilization, an oral formulation can be started. Morphine can be added if nitrates are ineffective; there may be some situations where morphine may be used alone (e.g., nitrates are contraindicated).[2]

Beta-blockers

Beta-blockers are recommended as front-line antianginal drugs.[2]​ Beta-blockers should be initiated within the first 24 hours for patients who do not have one or more of the following: signs of heart failure, evidence of a low output state, increased risk for cardiogenic shock, or other relative contraindications to beta-blockade (e.g., heart block, active asthma).[2]​ Intravenous administration is recommended in the emergency department when there is ongoing chest pain.[110]​ In other cases, oral treatment is sufficient.

Antiplatelet agents

All patients with suspected NSTE-ACS should be given a single loading dose of aspirin as soon as possible, unless they have significant bleeding risk or hypersensitivity to aspirin.

An oral P2Y12 inhibitor (e.g., clopidogrel, ticagrelor, prasugrel) is recommended, in addition to aspirin, for 12 months, unless there are contraindications such as excessive risk of bleeding.[1][2]​ Ticagrelor and prasugrel are associated with reduced ischemic events compared to clopidogrel, though there is also an increased bleeding risk with these agents.[111][112][113][114]

Ticagrelor is recommended, in the absence of contraindications, for all patients at moderate to high risk of ischemic events (e.g., elevated cardiac troponins) regardless of initial treatment strategy.[1][2]

Clopidogrel is recommended for patients who cannot receive ticagrelor or prasugrel. An increased loading dose of clopidogrel (or a supplementary dose at PCI following an initial dose) is recommended for patients scheduled for an invasive strategy when ticagrelor or prasugrel is not an option.[1]

Prasugrel is recommended in patients who are proceeding to PCI if there are no contraindications.[1][2][115]​ Prasugrel is contraindicated in patients with a history of ischemic stroke or transient ischemic attack, and its use is not recommended in patients ages >75 years or in patients with low body weight (<60 kg) due to increased bleeding risk (though dose reductions may mitigate this risk); therefore, ticagrelor is often more widely used.[1][93]​​[116]​​​[117][118]

Cangrelor is an intravenous adenosine triphosphate analog that binds reversibly to the platelet P2Y12 receptor and has a short half-life (<10 minutes).[1][119]​ It has been shown to reduce periprocedural death, myocardial infarction (MI), ischemia-driven revascularization, and stent thrombosis when compared with clopidogrel in patients undergoing PCI.[119][120]​​​ It is a second-line treatment option, although it may be used first-line in patients who are unable to take oral drug (i.e., sedated, unconscious, or vomiting).

P2Y12 inhibitors have a fast onset of action, allowing a loading dose administration after coronary angiography and directly before PCI. However, pretreatment with a P2Y12 inhibitor may be considered in selected cases and according to the bleeding risk, when the patient cannot undergo an early invasive strategy. In general, routine pretreatment with a P2Y12 receptor inhibitor, in addition to aspirin, is not recommended as it may be deleterious in patients who may have other causes of chest pain, such as aortic dissection. It is also not recommended if early invasive management is planned and coronary anatomy is not known.[1]​

Numerous trials of NSTE-ACS have shown benefit of glycoprotein IIb/IIIa inhibitors in reducing mortality and cardiovascular events, both in patients treated medically and in those who underwent PCI.[2]​ However, most, if not all, of the trials were conducted before P2Y12 inhibitors became routine therapy. Glycoprotein IIb/IIIa inhibitors reduce composite ischemic end-points, but increase the risk of bleeding.[2] [ Cochrane Clinical Answers logo ] ​ With no significant benefit of upstream use of a glycoprotein IIb/IIIa inhibitor in an invasive strategy, it is reasonable to withhold it until after invasive coronary angiography. A glycoprotein IIb/IIIa inhibitor (eptifibatide or tirofiban) can be administered to patients with NSTEMI and high-risk features (e.g., elevated troponin levels) who are not adequately pretreated with clopidogrel or ticagrelor, at the time of PCI.[2]​ In patients undergoing PCI and receiving clopidogrel, prasugrel, or ticagrelor, glycoprotein IIb/IIIa inhibitor use is recommended if there is a large thrombus burden, evidence of a no-reflow, or slow flow.[1][93][121]

Indications for invasive strategies

Acute MI should be suspected if the patient is clinically unstable. Emergent input from a cardiologist is needed to arrange emergent invasive coronary angiography (with the intent to perform revascularization); this is unlikely to be a feature of UA. See ST-elevation myocardial infarction and Non-ST-elevation myocardial infarction.

General recommendations for invasive coronary angiogram with or without revascularization in NSTE-ACS include:[1][2][93]​​ [ Cochrane Clinical Answers logo ]

  • An immediate invasive strategy (<2 hours) in patients with at least one of the following very high-risk criteria:

    • Ongoing or recurrent pain despite treatment

    • Hemodynamic instability (low blood pressure [BP] or shock) or cardiogenic shock; see  Shock

    • Recurrent dynamic ECG changes

    • Acute left ventricular failure, presumed secondary to ongoing myocardial ischemia; see  Acute heart failure

    • A life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation) or cardiac arrest after presentation; see  Sustained ventricular tachycardias

    • Mechanical complications such as new-onset mitral regurgitation

  • An early invasive strategy (<24 hours) in patients with at least one of the following high-risk criteria:

    • A confirmed diagnosis of NSTEMI based on current recommended high-sensitivity cardiac troponin (hs-cTn) algorithms

    • Dynamic ST- or T-wave changes (symptomatic or silent)

    • Transient ST-segment elevation

    • GRACE score >140

Patients who have no recurrence of symptoms and have none of the high- or very high-risk features are considered to be at low risk for acute ischemic events and can be managed by a selective invasive strategy.[1][106]​ Patients with UA have a significantly lower risk of death compared with those with NSTEMI and get less benefit from an emergent invasive approach.[94]​ An inpatient invasive strategy (coronary angiography within 72 hours of admission, with follow-on PCI if indicated) is generally recommended for patients with a working diagnosis of NSTE-ACS and a high index of suspicion for UA, particularly for those who have an intermediate or higher risk of adverse cardiovascular events.[1]

Patients who are on optimal medical therapy and are still having symptoms should be considered for cardiac catheterization; the exact timing of this is individualized, based on acuity and chronicity of symptoms. A noninvasive test for ischemia (preferably with imaging) is recommended in patients with none of the above-mentioned risk criteria and no recurrent symptoms, before deciding on an invasive evaluation.[1]

Following a selective invasive strategy, a coronary angiogram is usually carried out for recurring symptoms, objective evidence of ischemia on noninvasive testing, or detection of obstructive coronary artery disease (CAD) on coronary computed tomography angiography.[77]

The benefit of early revascularization in NSTE-ACS depends on the finding of a culprit lesion or coronary obstruction responsible for the clinical presentation. In more than one third of NSTE-ACS patients undergoing coronary angiography as part of an invasive strategy, no culprit lesion or target for revascularization is found.[122]

Ongoing medical treatment

The management of UA uses agents that stabilize the coronary plaque and prevent thrombus formation in an effort to avert or limit myocardial damage. The goal of pharmacologic anti-ischemic therapy is to decrease myocardial oxygen demand and to increase myocardial oxygen supply.

Anticoagulation

In patients with NSTE-ACS, anticoagulation is recommended for all patients, in addition to antiplatelet therapy, irrespective of the initial treatment strategy.[1][2]​​​ The options for anticoagulation include unfractionated heparin, a low molecular weight heparin (LMWH; e.g., enoxaparin), a selective factor Xa inhibitor (e.g., fondaparinux), or a direct thrombin inhibitor (e.g., bivalirudin).[1][2]​​​ Bivalirudin is a reasonable alternative to unfractionated heparin for patients undergoing PCI.[93]​ In aspirin-treated patients, short-term unfractionated heparin or LMHW (for up to 7 days) reduced the risk of MI, but there was a trend toward more major bleeds in the heparin studies compared with control studies.[123][124]​​​ Some studies have shown a benefit from short-term treatment in terms of mortality, although others have not.[123][124]​​​ For patients undergoing PCI, fondaparinux alone is no longer recommended due to a higher incidence of guiding-catheter thrombosis.[93][125][126]​​​

The intensity of antithrombotic treatment should be tailored to individual situations and risk of complications.[127]​ Triple therapy (antiplatelet agent, anticoagulation, and a glycoprotein IIb/IIIa inhibitor) is typically used in high-risk patients.[2]

Beta-blockers, calcium-channel blockers, nitrates

Beta-blockers are front-line antianginal drugs.[2]​ Beta-blockers should be initiated within the first 24 hours for patients who do not have one or more of the following: signs of heart failure, evidence of a low output state, increased risk for cardiogenic shock, or other relative contraindications to beta-blockade (e.g., heart block, active asthma).[1][2]

Nondihydropyridine calcium-channel blockers (i.e., diltiazem, verapamil) are recommended for symptom relief in patients with continuing chest pain or frequently recurring angina when beta-blockers are contraindicated and there is no left ventricular dysfunction.[2][110]​​​ There are only small randomized trials of calcium-channel blockers in non-STEMI. Generally they show efficacy in relieving symptoms, which seems to be equivalent to the efficacy of beta-blockers. However, calcium-channel blockers do not reduce mortality in unselected patients. Even so, both diltiazem and verapamil reduce combined end-points (long-term mortality and recurrent nonfatal MI) in patients with non-Q-wave MI without pulmonary congestion.[128] In patients without congestive heart failure who are undergoing thrombolysis for acute MI, the use of oral diltiazem did not reduce the cumulative occurrence of cardiac death, refractory ischemia, or nonfatal MI during 6 months' follow-up, but it did reduce the composite end point of nonfatal cardiac events, especially the need for myocardial revascularization.[129] Use of high-dose short-acting nifedipine (a dihydropyridine calcium-channel blocker) may have a detrimental effect on mortality in patients with CAD.[130]

Oral nitrates (preferably long-acting nitrates such as isosorbide mononitrate) can be used as second-line therapy for angina symptoms when calcium-channel blockers are contraindicated, poorly tolerated, or not achieving adequate symptomatic relief.[106]​ However, expert advice is that they are frequently used in clinical practice to provide continued symptomatic relief and prevention of angina.

Combination therapy is usually required in most patients (e.g., a beta-blocker plus a long-acting nitrate, or a calcium-channel blocker plus a long-acting nitrate). The combination of a beta-blocker and a dihydropyridine calcium-channel blocker is usually avoided in practice as using these agents together increases the risk of hypotension, bradycardia, atrioventricular (AV) block, and PR interval prolongation, and monitoring is required (e.g., BP, heart rate, ECG). Rarely, a combination of all three drug classes may be required with appropriate caution and monitoring.

ACE inhibitors

ACE inhibitors are indicated if hypertension persists despite treatment with nitrates, beta-blockers or calcium-channel blockers, or in patients with left ventricular systolic dysfunction or congestive heart failure.[2] They are beneficial in high-risk patients (those with a known history of CAD, stroke, peripheral vascular disease, or diabetes plus at least one other cardiovascular risk factor), including those with normal left ventricular function, and should be initiated 12-24 hours after presentation, in the absence of hypotension, hyperkalemia, and acute renal failure.[131]

Long-term management

Following stabilization in confirmed UA, patients should be started on long-term antianginal treatment.

Long-term antithrombotic therapy

  • Aspirin should be continued indefinitely. For patients with aspirin allergy, long-term ticagrelor or clopidogrel use is suggested, and in these patients, clopidogrel should also be continued indefinitely.

  • For UA/non-STEMI patients treated medically without stenting, aspirin should be given indefinitely and clopidogrel or ticagrelor should normally be prescribed for up to 12 months.[2]

  • For UA/non-STEMI patients treated with either bare metal stent (BMS) or drug-eluting stent (DES), aspirin should be continued indefinitely. Clopidogrel, prasugrel, or ticagrelor should be given for at least 12 months in patients with DES and up to 12 months in patients receiving BMS.[2]

    • In selected patients undergoing PCI, shorter-duration dual antiplatelet therapy (1–3 months) is reasonable, with subsequent transition to P2Y12 inhibitor monotherapy to reduce the risk of bleeding events.[93]

  • For patients with coronary artery disease, use of low-dose rivaroxaban (a direct oral anticoagulant) may be considered in combination with low-dose aspirin for 12 months.[1][132]

  • In patients who are event-free after 3-6 months of dual antiplatelet therapy (DAPT) and who are not high ischemic risk, single agent antiplatelet therapy (preferably with a P2Y12 receptor inhibitor) can be considered.[1]​ In patients with a high bleeding risk, monotherapy with aspirin or P2Y12 receptor inhibitor may be considered after 1 month of DAPT.[1]

    • De-escalation of P2Y12 receptor inhibitor treatment (e.g., with a switch from prasugrel/ticagrelor to clopidogrel) may also be considered as an alternative DAPT strategy to reduce bleeding risk.[1]

    • De-escalation of antiplatelet therapy is not recommended in the first 30 days after an ACS event.[1]

  • For patients with CAD, use of low-dose rivaroxaban (a direct oral anticoagulant) may be considered in combination with low-dose aspirin for 12 months.[1][132]

Long-term management of lipids

  • In the absence of contraindications, high-intensity statin therapy (i.e., statin regimens that reduce low-density lipoprotein [LDL] cholesterol by ≥50%) should be started as soon as possible after admission in all NSTE-ACS patients.[1]

  • For secondary prevention, treatment of patients who have atherosclerotic cardiovascular disease (ASCVD) depends on their risk of future ASCVD events.[1][133][134][135]

    • Patients are considered to be at very high risk of future events if they have a history of multiple major ASCVD events (recent acute coronary syndrome [within the past 12 months], MI other than the recent acute coronary syndrome, ischemic stroke, symptomatic peripheral arterial disease [claudication with ankle brachial index <0.85, previous revascularization or amputation]) or one major ASCVD event and multiple high risk conditions (age ≥65 years, heterozygous family history, history of previous coronary artery bypass graft or PCI, diabetes mellitus, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-cholesterol [≥100 mg/dL {≥2.6 mmol/L}] despite maximally tolerated therapy, history of congestive heart failure). Patients at very high risk of future events should receive high-intensity statin therapy or maximal statin therapy.[133] Ezetimibe may be added if the patient is on maximal statin therapy and LDL-cholesterol level remains ≥55 mg/dL (≥1.4 mmol/L). 

    • A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibody (e.g., evolocumab, alirocumab) may be added to maximal statin and ezetimibe therapy if LDL-cholesterol level continues to remain ≥55 mg/dL (≥1.4 mmol/L).

    • In patients not at very high risk of future events, high-intensity statin therapy should be initiated and continued in those up to 75 years of age, with the aim of achieving a 50% or greater reduction in LDL-cholesterol levels. Moderate-intensity statin therapy may be used (reducing LDL-cholesterol by 30% to <50%) if high-intensity statin therapy is not tolerated. Ezetimibe may be added if the patient is on maximal statin therapy and LDL-cholesterol level remains ≥55 mg/dL (≥1.4 mmol/L). In patients older than 75 years, moderate- or high-intensity statin therapy should be considered.

Beta-blockers

  • Unless contraindicated, beta-blockers should be continued indefinitely in patients with reduced left ventricular function, with or without symptoms of heart failure.[1] In other patients, beta-blockers may be useful, but evidence of their long-term benefit is less well established.

ACE inhibitors

  • Unless contraindicated, long-term use of ACE inhibitors is indicated in patients with a left ventricular ejection fraction of 40% or less and also in patients with diabetes mellitus, hypertension, or chronic kidney disease.[1]

  • ACE inhibitors should be considered for all other patients to prevent recurrence of ischemic events.[2]

Long-term anti-ischemic therapy

  • Long-term anti-ischemic therapy in patients with stable ischemic heart disease should be individualized based on patient characteristics and clinical factors (e.g., heart rate, blood pressure, left ventricular function) and preferences.

  • Anti-ischemic treatment options include beta-blockers, nitrates, calcium-channel blockers, ivabradine, and ranolazine.[106]

See Chronic coronary disease.

Cardiac rehabilitation

In addition to adequate control of hypertension, diabetes mellitus, and hyperlipidemia, risk-factor intervention is recommended.[1] This includes lifestyle modifications (smoking cessation; regular physical activity, with 30 minutes of moderate-intensity aerobic activity at least 5 times/week; a healthy diet based on low salt intake, a decreased intake of saturated fats, and a regular intake of fruit and vegetables; and weight reduction).[26][106][136]​​

Use of this content is subject to our disclaimer