Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

presumed cardiac chest pain

1st line – nitrate and/or morphine ± oxygen

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INITIAL
|
presumed cardiac chest pain
1st line – 

nitrate and/or morphine ± oxygen

All patients with signs/symptoms of acute coronary syndrome (ACS) without ST-elevation on ECG should be treated as a presumed diagnosis of non-ST-elevation acute coronary syndrome (NSTE-ACS) until the results of cardiac biomarkers are known.

Pain relief with a sublingual nitrate 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 unstable angina. 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]

Supplemental oxygen should be given to patients with non-ST-elevation acute coronary syndromes with arterial saturation <90%, respiratory distress, or other high-risk features of hypoxemia.[2]

Primary options

nitroglycerin: 0.3 to 0.6 mg (tablets) sublingually every 5 minutes when required, maximum 3 doses in 15 minutes; or 400-800 micrograms (1-2 sprays) sublingually every 3-5 minutes when required, maximum 3 doses in 15 minutes

and/or

morphine sulfate: 2-5 mg intravenously every 5-30 minutes when required

Secondary options

nitroglycerin: 5 micrograms/minute intravenous infusion initially, increase by 5 micrograms/minute increments every 3-5 minutes according to response up to 20 micrograms/minute, if no response may increase by 10-20 micrograms/minute every 3-5 minutes, maximum 100 micrograms/minute

and/or

morphine sulfate: 2-5 mg intravenously every 5-30 minutes when required

Plus – beta-blocker

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INITIAL
|
presumed cardiac chest pain
Plus – 

beta-blocker

Treatment recommended for ALL patients in selected patient group

Beta-blockers are front-line anti-anginal 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]

Intravenous administration is recommended in the emergency department when there is ongoing chest pain.[110] In other cases, oral treatment is sufficient.

Primary options

metoprolol succinate: 100-400 mg orally (extended-release) once daily

OR

metoprolol tartrate: 50-200 mg orally (immediate-release) twice daily; 2.5 to 5 mg intravenously every 10 minutes when required, maximum 15 mg/total dose

OR

bisoprolol: 5-20 mg orally once daily

OR

carvedilol: 12.5 to 50 mg orally twice daily

Plus – antiplatelet therapy

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INITIAL
|
presumed cardiac chest pain
Plus – 

antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

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.

A P2Y12 inhibitor (e.g., ticagrelor, prasugrel, clopidogrel) is recommended, in addition to aspirin, for 12 months, unless there are contraindications such as excessive risk of bleeding.[1][2]​

Ticagrelor is recommended, in the absence of contraindications, for 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 percutaneous coronary intervention [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, an intravenous adenosine triphosphate analog that binds reversibly to the platelet P2Y12 receptor and has a short half-life (<10 minutes), may be considered in P2Y12 inhibitor-naive patients undergoing PCI.[1][119]​ It has been shown to reduce periprocedural death, myocardial infarction, 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 medication (i.e., sedated, unconscious, or vomiting).

Primary options

conservative strategy

aspirin: 162-325 mg orally as a loading dose

and

ticagrelor: 180 mg orally as a loading dose

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose

-- AND --

prasugrel: 60 mg orally as a loading dose

or

ticagrelor: 180 mg orally as a loading dose

Secondary options

conservative strategy

aspirin: 162-325 mg orally as a loading dose

and

clopidogrel: 300 mg orally as a loading dose

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose

and

clopidogrel: 600 mg orally as a loading dose (or 300 mg prior to PCI and 300 mg at time of PCI)

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose

and

cangrelor: 30 micrograms/kg intravenously initially (before PCI), followed immediately by 4 micrograms/kg/minute infusion for at least 2 hours or the duration of PCI (whichever is longer)

OR

aspirin-allergic patients

ticagrelor: conservative strategy or PCI planned: 180 mg orally as a loading dose

or

clopidogrel: conservative strategy: 300 mg orally as a loading dose; PCI planned: 600 mg orally as a loading dose (or 300 mg prior to PCI and 300 mg at time of PCI)

or

prasugrel: PCI planned: 60 mg orally as a loading dose

or

cangrelor: PCI planned: 30 micrograms/kg intravenously initially (before PCI), followed immediately by 4 micrograms/kg/minute infusion for at least 2 hours or the duration of PCI (whichever is longer)

ACUTE

non-ST-elevation acute coronary syndrome

1st line – early coronary catheterization ± revascularization

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ACUTE
|
non-ST-elevation acute coronary syndrome
1st line – 

early coronary catheterization ± revascularization

General recommendations for invasive coronary angiogram with or without revascularization in NSTE-ACS include the two strategies below.[1]​​ [ Cochrane Clinical Answers logo ]

Strategy 1: an immediate invasive strategy (<2 hours) is recommended 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; acute left ventricular failure, presumed secondary to ongoing myocardial ischemia; a life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation); mechanical complications such as new-onset mitral regurgitation.[1]

Strategy 2: an early invasive strategy (<24 hours) is recommended in patients with at least one of the following high-risk criteria: confirmed diagnosis of non-ST-elevation myocardial infarction (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; Global Registry of Acute Coronary Events (GRACE) score >140.[1]

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]

Patients with UA have a significantly lower risk of death compared with those with NSTEMI and get less benefit from an immediate 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 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.

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 on coronary computed tomography angiography.

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]

Plus – antiplatelet therapy

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ACUTE
|
non-ST-elevation acute coronary syndrome
Plus – 

antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

Aspirin is recommended for all UA/NSTEMI patients without contraindications.[1]

A P2Y12 inhibitor (e.g., ticagrelor, prasugrel, clopidogrel) is recommended, in addition to aspirin, for 12 months, unless there are contraindications such as excessive risk of bleeding.[1][2]

Ticagrelor is recommended, in the absence of contraindications, for 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, an intravenous adenosine triphosphate analog that binds reversibly to the platelet P2Y12 receptor and has a short half-life (<10 minutes), may be considered in P2Y12 inhibitor-naive patients undergoing PCI.[1][119]​ It has been shown to reduce periprocedural death, 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 medication (i.e., sedated, unconscious, or vomiting).

P2Y12 inhibitors have a fast onset of action, allowing a loading dose administration following 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.

Primary options

conservative strategy

aspirin: 162-325 mg orally as a loading dose, followed by 81-162 mg once daily

and

ticagrelor: 180 mg orally as a loading dose, followed by 90 mg twice daily

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose, followed by 81-162 mg once daily

-- AND --

prasugrel: 60 mg orally as a loading dose, followed by 10 mg once daily

or

ticagrelor: 180 mg orally as a loading dose, followed by 90 mg twice daily

Secondary options

conservative strategy

aspirin: 162-325 mg orally as a loading dose, followed by 81-162 mg once daily

and

clopidogrel: 300 mg orally as a loading dose, followed by 75 mg once daily

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose, followed by 81-162 mg once daily

and

clopidogrel: 600 mg orally as a loading dose (or 300 mg prior to PCI and 300 mg at time of PCI), followed by 75 mg once daily

OR

PCI planned

aspirin: 162-325 mg orally as a loading dose, followed by 81-162 mg once daily

and

cangrelor: 30 micrograms/kg intravenously initially (before PCI), followed immediately by 4 micrograms/kg/minute infusion for at least 2 hours or the duration of PCI (whichever is longer)

OR

aspirin-allergic patients

ticagrelor: conservative strategy or PCI planned: 180 mg orally as a loading dose, followed by 90 mg twice daily

or

clopidogrel: conservative strategy: 300 mg orally as loading dose, followed by 75 mg once daily; PCI planned: 600 mg orally as a loading dose (or 300 mg prior to PCI and 300 mg at time of PCI), followed by 75 mg once daily

or

prasugrel: PCI planned: 60 mg orally as a loading dose, followed by 10 mg once daily

or

cangrelor: PCI planned: 30 micrograms/kg intravenously initially (before PCI), followed immediately by 4 micrograms/kg/minute infusion for at least 2 hours or the duration of PCI (whichever is longer)

Plus – anticoagulation

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ACUTE
|
non-ST-elevation acute coronary syndrome
Plus – 

anticoagulation

Treatment recommended for ALL patients in selected patient group

Anticoagulation is recommended for all patients, in addition to antiplatelet therapy, irrespective of the initial treatment strategy.[1][2]

Options for anticoagulation include unfractionated heparin, a low molecular weight heparin (LMWH; e.g., enoxaparin), 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 LMWH (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 (a selective factor Xa inhibitor) 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 agents, heparin, and glycoprotein IIb/IIIa inhibitors) is typically used in high-risk patients.[2]

Primary options

heparin: 60 units/kg (maximum 5000 units) intravenous bolus initially, followed by 12 units/kg/hour (maximum 1000 units/hour) intravenous infusion, adjust dose to target aPTT, continue for at least 48 hours or until hospital discharge or PCI is performed

OR

enoxaparin: 1 mg/kg subcutaneously every 12 hours, continue for at least 48 hours or until hospital discharge or PCI is performed

OR

bivalirudin: consult specialist for guidance on dose

Secondary options

fondaparinux: 2.5 mg subcutaneously once daily, continue until hospital discharge

Plus – beta-blocker and/or calcium-channel blocker and/or nitrate

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ACUTE
|
non-ST-elevation acute coronary syndrome
Plus – 

beta-blocker and/or calcium-channel blocker and/or nitrate

Treatment recommended for ALL patients in selected patient group

Beta-blockers are front-line anti-anginal 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]

Intravenous administration is recommended in the emergency department when there is ongoing chest pain.[110] In other cases, oral treatment is sufficient.

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-ST-elevation myocardial infarction. 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 myocardial infarction [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 coronary artery disease.[130]

Oral nitrates (preferably long-acting nitrates, such as isosorbide mononitrate) can be used 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, 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.

Primary options

metoprolol succinate: 100-400 mg orally (extended-release) once daily

OR

metoprolol tartrate: 50-200 mg orally (immediate-release) twice daily; 2.5 to 5 mg intravenously every 10 minutes when required, maximum 15 mg/total dose

OR

bisoprolol: 5-20 mg orally once daily

OR

carvedilol: 12.5 to 50 mg orally twice daily

Secondary options

diltiazem: 180-360 mg/day orally (immediate-release) given in 3-4 divided doses; 120-480 mg (extended-release) once daily

OR

verapamil: 80-120 mg orally (immediate-release) three times daily, maximum 480 mg/day

Tertiary options

isosorbide mononitrate: 20 mg orally (immediate-release) twice daily; 30-120 mg orally (extended-release) once daily in the morning

More

Consider – glycoprotein IIb/IIIa inhibitor

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ACUTE
|
non-ST-elevation acute coronary syndrome
Consider – 

glycoprotein IIb/IIIa inhibitor

Treatment recommended for SOME patients in selected patient group

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.[93][121]

Primary options

eptifibatide: 180 micrograms/kg (maximum 22.6 mg) intravenous bolus initially, followed by 2 micrograms/kg/minute (maximum 15 mg/hour) intravenous infusion, a second bolus dose of 180 micrograms/kg (maximum 22.6 mg) should be administered 10 minutes after the first bolus, continue infusion for up to 18-24 hours after PCI

OR

tirofiban: 25 micrograms/kg intravenous bolus initially, followed by 0.15 micrograms/kg/minute intravenous infusion for up to 18 hours

Consider – ACE inhibitor

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ACUTE
|
non-ST-elevation acute coronary syndrome
Consider – 

ACE inhibitor

Treatment recommended for SOME patients in selected patient group

Indicated if hypertension persists despite treatment with nitrates or beta-blockers or calcium-channel blockers, or in patients with left ventricular systolic dysfunction or congestive heart failure.[2]

ACE inhibitors are beneficial in high-risk patients (known history of coronary artery disease, 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]

Primary options

perindopril erbumine: 4-16 mg orally once daily

OR

ramipril: 2.5 to 20 mg orally once daily

OR

enalapril: 10-20 mg orally once daily

OR

captopril: 25-50 mg orally three times daily

OR

lisinopril: 5-40 mg orally once daily

ONGOING

poststabilization: confirmed UA (nonelevated cardiac biomarkers)

1st line – antithrombotic therapy

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ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
1st line – 

antithrombotic therapy

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

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. Prasugrel may be used in these patients treated with a stent.

Duration of long-term antiplatelet therapy: for UA/non-ST-elevation myocardial infarction (non-STEMI) patients treated medically without stenting, aspirin should be given indefinitely and clopidogrel or ticagrelor should 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 percutaneous coronary intervention, 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]

In patients who are event-free after 3-6 months of dual antiplatelet therapy (DAPT) and who are not high ischemic risk, single 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 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]

Primary options

Without stenting

aspirin: 81-325 mg orally once daily

More

-- AND --

clopidogrel: 75 mg orally once daily

or

ticagrelor: 90 mg orally twice daily

OR

With stenting

aspirin: 81-325 mg orally once daily

More

-- AND --

clopidogrel: 75 mg orally once daily

or

prasugrel: 10 mg orally once daily

or

ticagrelor: 90 mg orally twice daily

OR

Aspirin-allergic patients without stenting

clopidogrel: 75 mg orally once daily

or

ticagrelor: 90 mg orally twice daily

OR

Aspirin-allergic patients with stenting

clopidogrel: 75 mg orally once daily

or

prasugrel: 10 mg orally once daily

or

ticagrelor: 90 mg orally once daily

Secondary options

aspirin: 75-100 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

Plus – statin

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ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

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.[133]

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], myocardial infarction 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 percutaneous intervention, 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]

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. In patients older than 75 years, moderate- or high-intensity statin therapy should be considered.[133]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

Secondary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – ezetimibe

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ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

For patients at very high risk of future events, and those up to 75 years of age and not at very high risk, ezetimibe may be added if the patient is on maximal statin therapy and LDL-cholesterol level remains ≥55 mg/dL (≥1.4 mmol/L).[1][133][134][135]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

In patients at very high risk of future events, a PCSK9 inhibitor monoclonal antibody may be added to maximal statin and ezetimibe therapy if LDL-cholesterol level remains ≥55 mg/dL (≥1.4 mmol/L).[1][133][134][135]

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Consider – beta-blocker

Back
ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Consider – 

beta-blocker

Treatment recommended for SOME patients in selected patient group

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.

Primary options

metoprolol succinate: 100-400 mg orally (extended-release) once daily

OR

metoprolol tartrate: 50-200 mg orally (immediate-release) twice daily

OR

bisoprolol: 5-20 mg orally once daily

OR

carvedilol: 12.5 to 50 mg orally twice daily

Consider – ACE inhibitor

Back
ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Consider – 

ACE inhibitor

Treatment recommended for SOME patients in selected patient group

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]

Primary options

perindopril erbumine: 4-16 mg orally once daily

OR

ramipril: 2.5 to 20 mg orally once daily

OR

enalapril: 10-20 mg orally once daily

OR

captopril: 25-50 mg orally three times daily

OR

lisinopril: 5-40 mg orally once daily

Consider – anti-ischemic therapy

Back
ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Consider – 

anti-ischemic therapy

Treatment recommended for SOME patients in selected patient group

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 artery disease.

Plus – cardiac rehabilitation

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ONGOING
|
poststabilization: confirmed UA (nonelevated cardiac biomarkers)
Plus – 

cardiac rehabilitation

Treatment recommended for ALL patients in selected patient group

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]​​

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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