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

ACUTE

acute presentation

1st line – antiplatelet therapy

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ACUTE
|
acute presentation
1st line – 

antiplatelet therapy

Aspirin is indicated immediately for all patients suspected of having an acute coronary syndrome (ACS) unless contraindicated or already taken.[2]​​​ Healthcare personnel providing prehospital emergency services should give a single loading dose of aspirin to patients presenting with chest pain, suspected of having ACS unless contraindicated or already taken by the patient.[2]​​​ High-dose aspirin is associated with an increased risk of bleeding when compared with low-dose aspirin and in the absence of improved outcomes.[2]

All patients should be given dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. If the patient is intolerant of aspirin or it is otherwise contraindicated, a P2Y12 inhibitor can be given alone, but two different P2Y12 inhibitors should not be given together. P2Y12 inhibitors can reduce mortality and morbidity, but they may be associated with increased bleeding risk.[115][116]​​​ Ticagrelor and prasugrel are associated with reduced ischemic events compared to clopidogrel, and recommended in patients undergoing percutaneous coronary intervention (PCI), although there is also an increased bleeding risk with these drugs.[2][117][118][119][120][121][122][123]​​​ Ticagrelor is recommended for patients on either invasive or noninvasive strategies.[2][5]​​​ Prasugrel is recommended only for patients on an invasive strategy.[2][5][124]​​​​ Clopidogrel is recommended for patients who cannot receive ticagrelor or prasugrel, and in older patients (≥70 years).[5][125]​​​ Prasugrel is contraindicated in patients with a history of ischemic stroke or transient ischemic attack, and its use is not recommended in patients ≥75 years of age 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.​[97][126][127][128]

Routine pretreatment with a P2Y12 inhibitor is not recommended if early invasive management is planned and coronary anatomy is not known.[5][132]​ For patients receiving chronic clopidogrel therapy prior to presentation, there is some evidence to suggest decreased periprocedural MI with clopidogrel reloading at the time of PCI.[133]

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

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

Consider – oxygen

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ACUTE
|
acute presentation
Consider – 

oxygen

Treatment recommended for SOME patients in selected patient group

All patients require oxygen saturation measurement using pulse oximetry.[2] Guidelines recommend supplemental oxygen therapy only in patients with an arterial oxygen saturation <90%, respiratory distress, or other high-risk features for hypoxemia.[2][5]

Plus – pain relief

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ACUTE
|
acute presentation
Plus – 

pain relief

Treatment recommended for ALL patients in selected patient group

Pain relief is indicated in the initial management of all patients.

Sublingual nitroglycerin reduces myocardial oxygen demand and enhances myocardial oxygen delivery. Nitroglycerin is contraindicated if there is hypotension, marked bradycardia or tachycardia, known severe aortic stenosis, right ventricular infarction, and/or a history of recent phosphodiesterase-5 inhibitor use (e.g., sildenafil, tadalafil, vardenafil, avanafil) for erectile dysfunction in the last 24-48 hours.[5]​ Intravenous nitroglycerin is indicated if 3 doses of sublingual nitroglycerin have not relieved the pain.

Morphine should be added early if nitroglycerin is not sufficient. Morphine, in addition to its analgesic and anxiolytic properties, has hemodynamic effects that are potentially beneficial in unstable angina and non-ST-elevation myocardial infarction (NSTEMI).

Morphine causes vasodilation and may produce reductions in heart rate (through increased vagal tone) and systolic BP to further reduce myocardial oxygen demand.[88]​ If nitroglycerin is not effective or is contraindicated, morphine can be given as an alternative in the absence of any contraindications. Limited data (largely observational studies) investigate morphine use for NSTEMI with evidence of potential safety concerns, thus it should be used with caution.[134] One randomized, double-blind trial found that morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction.[135]

Primary options

nitroglycerin: 400-800 micrograms (1-2 sprays) every 5 minutes, maximum 3 doses

OR

nitroglycerin: 0.3 to 0.6 mg sublingually every 5 minutes, maximum 3 doses

Secondary options

nitroglycerin: 5 micrograms/min intravenously initially, increase by 5-20 micrograms/min increments every 3-5 minutes, maximum 200 micrograms/min

Tertiary options

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

and

nitroglycerin: 5 micrograms/min intravenously initially, increase by 5-20 micrograms/min increments every 3-5 minutes, maximum 200 micrograms/min

OR

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

Plus – beta-blocker

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ACUTE
|
acute presentation
Plus – 

beta-blocker

Treatment recommended for ALL patients in selected patient group

Oral beta-blockers should be started as soon as a patient with non-ST-elevation myocardial infarction is hemodynamically stable unless there are contraindications (e.g., heart block, active asthma), as they decrease infarct size and reduce mortality.[88]​[2]​​[138]

Treatment should begin within a few days of the event, if not initiated acutely, and should be continued indefinitely, especially in patients with reduced left ventricular function.

Evidence suggests that a beta-blocker may reduce the short-term risk of a reinfarction and the long-term risk of all‐cause mortality and cardiovascular mortality in patients with acute myocardial infarction (MI).[139][140][141]​ Randomized trials with threatened or evolving MI have shown lower rates of progression to MI with beta-blocker treatment.[142][143]​​ Comparative studies between the various beta-blockers in the acute setting are lacking. However, beta-blockers without intrinsic sympathomimetic activity (e.g., metoprolol, propranolol, and atenolol) are preferred for initial management.

Selection of a long-term beta-blocker often depends on the clinician's familiarity with the agent. The goal resting heart rate is 50-60 bpm.[88]​​[187]

Primary options

metoprolol tartrate: 50-100 mg orally (regular-release) twice daily

OR

atenolol: 50-100 mg/day orally

OR

propranolol hydrochloride: 180-320 mg/day orally (immediate-release) given in 3-4 divided doses

Consider – calcium-channel blocker

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ACUTE
|
acute presentation
Consider – 

calcium-channel blocker

Treatment recommended for SOME patients in selected patient group

Calcium-channel blockers can be given to patients with continuing or recurrent ischemic symptoms after being given adequate nitrate and beta-blocker therapy, or those who cannot tolerate beta-blockers.[88]​ Although they are often used, they are no more effective than control at reducing mortality or myocardial infarction rates in people with unstable angina.

Patients treated acutely with a calcium-channel blocker for acute angina do not need to continue these drugs, provided there is no recurrent angina on drug cessation or another indication for these drugs (i.e., hypertension). These drugs can be tapered after 24 hours at the discretion of the clinician.

Short-acting dihydropyridines (e.g., nifedipine) should be avoided in the absence of adequate beta-blocker therapy because they may be associated with adverse outcomes.[88]

Verapamil or diltiazem should be avoided in severe left ventricular dysfunction.[88]

Primary options

diltiazem: 30-90 mg orally (immediate-release) four times daily

OR

verapamil: 80-120 mg orally (immediate-release) three times daily

OR

amlodipine: 5-10 mg orally once daily

Plus – assess need for invasive or conservative approach

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ACUTE
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acute presentation
Plus – 

assess need for invasive or conservative approach

Treatment recommended for ALL patients in selected patient group

Urgent and immediate angiography is indicated if the patient is clinically unstable or has any very high-risk features: ongoing or recurrent pain despite treatment, hemodynamic instability (low blood pressure or shock) or cardiogenic shock, recurrent dynamic ECG changes suggestive of ischemia, a life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation) or cardiac arrest after presentation, or mechanical complications such as new onset mitral regurgitation.[2][5][97]

In the absence of very high-risk features or clinical instability, the decision to pursue an invasive approach or medical management is made on an individual basis.[2][86][188]​​ Guidelines recommend an early invasive approach leading to revascularization in patients who are at intermediate or high risk of ischemic events, and a routine invasive or selective invasive approach with further risk stratification in patients with low risk of further adverse cardiac events.[2]​ High-risk patients should undergo early (12-24 hours) coronary angiography and angiographically directed revascularization if possible unless patients have serious comorbidities, including cancer or end-stage liver disease, or clinically obvious contraindications, including acute or chronic (chronic kidney disease 4 or higher) renal failure, multiorgan failure, or medical frailty.[2][86]​​[89]​​[145]

General recommendations for invasive coronary angiogram and revascularization in non-ST-elevation acute coronary syndromes include the following three approaches.[5][97] [ Cochrane Clinical Answers logo ]

1) An immediate invasive strategy (<2 hours) in patients with at least one of the following very high-risk criteria: ongoing or recurrent chest pain despite treatment; hemodynamic instability (low blood pressure) or cardiogenic shock; recurrent dynamic ECG changes or ongoing chest pain refractory to medical treatment; acute left ventricular failure, presumed secondary to ongoing myocardial ischemia; life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation) or cardiac arrest after presentation; or mechanical complications such as new onset or worsening mitral regurgitation or acute pulmonary edema.

2) An early invasive strategy (<24 hours) in patients with at least one of the following high-risk criteria: a confirmed diagnosis of non-ST-elevation myocardial infarction based on current recommended high-sensitive troponin assays algorithms; dynamic ST- or T-wave changes (symptomatic or silent); transient ST-elevation, Global Registry of Acute Coronary Events (GRACE) score >140 or steeply rising Tn values on serial testing despite optimized medical therapy.

3) Patients with no recurrence of symptoms and none of the high or very high-risk features are considered at low risk for acute ischemic events and can be managed by a selective invasive strategy which may be reasonable to perform prior to hospital discharge.[2][5][146]​ Patients who are on optimal medical therapy and are still having symptoms and/or those with large areas of ischemia (>10% of left ventricular myocardium) should be considered for revascularization.[146]​ 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.[5]

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.

Plus – percutaneous coronary intervention (PCI)

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ACUTE
|
acute presentation
|
invasive approach planned
Plus – 

percutaneous coronary intervention (PCI)

Treatment recommended for ALL patients in selected patient group

PCI involves angioplasty, alone or in combination with placement of a stent, capable of relieving coronary narrowing or occlusion.[97] Radial artery access is preferred when possible as it decreases procedural site complications.[2][97][155]​​

Complications of PCI include PCI-induced myocardial infarction; coronary perforation, dissection, or rupture; cardiac tamponade; malignant arrhythmias; cholesterol emboli; and bleeding from the access site. At experienced high-volume sites, radial artery access is preferred due to decreased access site complications.[155]

Contrast-induced nephropathy is a common and potentially serious complication, especially in patients with baseline impaired renal function.[156] Stent thromboses (early and late) are a catastrophic complication.

In patients with multivessel disease who are undergoing immediate invasive treatment and in cardiogenic shock, routine PCI of a nonculprit artery should not be performed due to the increased risk of kidney failure or death.[2]

Plus – anticoagulation

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ACUTE
|
acute presentation
|
invasive approach planned
Plus – 

anticoagulation

Treatment recommended for ALL patients in selected patient group

Anticoagulation treatment should be added to antiplatelet therapy at the earliest recognition (or suspicion) of non-ST-elevation myocardial infarction. This can be with subcutaneous low-molecular-weight heparin (LMWH) (e.g., enoxaparin, dalteparin), intravenous unfractionated heparin (UFH), or bivalirudin, and therapy can be continued throughout hospitalization or until the time of percutaneous coronary intervention (PCI).[137] Although UFH has traditionally been the preferred anticoagulant to support PCI, intravenous enoxaparin may be considered as an alternative.[2]​ Fondaparinux alone is no longer recommended due to a higher incidence of guiding-catheter thrombosis.[97] Bivalirudin is a reasonable alternative to unfractionated heparin for patients undergoing PCI.[97]​ The anticoagulant is used in conjunction with antiplatelet therapy already started.[2][5]​​​ Anticoagulation should not be given if there are contraindications: namely, major bleeding, or history of adverse drug reaction or heparin-induced thrombocytopenia.

The antiplatelet and anticoagulation regimens should be started before the diagnostic angiogram (i.e., upstream).

UFH and LMWH are thrombin inhibitors. Like heparin, their mechanism of action involves binding to antithrombin III to increase its anticoagulant activity.

UFH and LMWH are contraindicated in patients with major bleeding, history of adverse drug reaction, or heparin-induced thrombocytopenia.

Creatinine clearance should be assessed before administering enoxaparin. Patients with severe renal impairment (creatinine clearance <30 mL/minute) should be considered for UFH over enoxaparin, or a dose reduction may be required in these patients.

Primary options

heparin: 60 units/kg intravenous bolus initially, followed by 12 units/kg/hour infusion, adjust dose to target aPTT of 50-75 seconds

OR

enoxaparin: 30 mg intravenous bolus initially, followed by 1 mg/kg subcutaneously every 12 hours

OR

dalteparin: 120 units/kg subcutaneously every 12 hours, maximum 10,000 units twice daily

OR

bivalirudin: 0.1 mg/kg intravenous bolus, followed by 0.25 mg/kg/hour intravenous infusion until diagnostic angiography or PCI is performed

Consider – glycoprotein IIb/IIIa inhibitor

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ACUTE
|
acute presentation
|
invasive approach planned
Consider – 

glycoprotein IIb/IIIa inhibitor

Treatment recommended for SOME patients in selected patient group

Addition of a glycoprotein IIb/IIIa inhibitor is recommended if there is a large thrombus burden, evidence of a no-reflow, or slow flow at percutaneous coronary intervention.[97]​ Glycoprotein IIb/IIIa inhibitors block platelet binding of fibrinogen to the glycoprotein IIb/IIIa receptor.​​ This is the final stage before platelet aggregation and the formation of thrombus.

Tirofiban or eptifibatide are the preferred options if glycoprotein IIb/IIIa inhibitor administration is planned.[153][154]​ 

Primary options

eptifibatide: 180 micrograms/kg intravenous bolus initially at time of percutaneous coronary intervention, followed by 2 micrograms/kg/min infusion for up to 18-24 hours and a second bolus of 180 micrograms/kg/dose 10 minutes after the initial bolus

OR

tirofiban: 0.4 micrograms/kg/min intravenous infusion for 30 minutes, followed by 0.1 micrograms/kg/min

Plus – anticoagulation

Back
ACUTE
|
acute presentation
|
invasive approach not planned
Plus – 

anticoagulation

Treatment recommended for ALL patients in selected patient group

Anticoagulation therapy can be with subcutaneous low molecular weight heparin (LMWH) (e.g., enoxaparin, dalteparin), or intravenous unfractionated heparin (UFH), or fondaparinux, and therapy can be continued throughout hospitalization or until the time of percutaneous coronary intervention, if this is subsequently planned.[137]​ The anticoagulant is used in conjunction with antiplatelet therapy already started.[2][5]

Anticoagulation should not be given if there are contraindicated: namely, major bleeding or history of adverse drug reaction or heparin-induced thrombocytopenia.

UFH and LMWH are thrombin inhibitors. Like heparin, their mechanism of action involves binding to antithrombin III to increase its anticoagulant activity. UFH and LMWH are contraindicated in patients with major bleeding, history of adverse drug reaction, or heparin-induced thrombocytopenia.

Creatinine clearance should be assessed before administering enoxaparin. Patients with severe renal impairment (creatinine clearance <30 mL/minute) should be considered for UFH over enoxaparin, or a dose reduction may be required in these patients.

If the treatment program changes and percutaneous coronary intervention is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis.[2]

Primary options

heparin: 60 units/kg intravenous bolus initially, followed by 12-15 units/kg/hour infusion, adjust dose to target aPTT of 50-75 seconds

OR

enoxaparin: 30 mg intravenous bolus initially, followed by 1 mg/kg subcutaneously every 12 hours

OR

dalteparin: 120 units/kg subcutaneously every 12 hours, maximum 10,000 units twice daily

OR

fondaparinux: 2.5 mg subcutaneously once daily for up to 8 days

ONGOING

post-stabilization

1st line – cardiac rehabilitation

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ONGOING
|
post-stabilization
1st line – 

cardiac rehabilitation

The aims of cardiac rehabilitation are to increase functional capacity; stop cigarette smoking; modify lipids and lipoproteins; decrease body weight and fat stores; reduce blood pressure; improve psychosocial wellbeing; prevent progression and promote plaque stability; induce regression of underlying atherosclerosis; and restore and maintain optimal physical, psychological, emotional, social, and vocational functioning.[158][160]​​​​

Cardiac rehabilitation should be started on discharge and after clearance by an outpatient physician.[158]​ The basic prescription should include aerobic and weight-bearing exercise 4 to 5 times per week for >30 minutes. There is a risk of triggering a recurrent myocardial infarction with physical activity. However, this is minimal and reduced by using a structured program to minimize (and treat) this risk.[160]

Plus – continue antiplatelet therapy

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ONGOING
|
post-stabilization
Plus – 

continue antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

Aspirin should be continued indefinitely at a low dose if the patient is tolerant and not contraindicated. A P2Y12 inhibitor should be continued for up to 12 months. For patients with aspirin allergy, long-term P2Y12 inhibitor use is suggested.[2][5][161][162]

In selected patients who have had percutaneous coronary intervention, shorter-duration dual antiplatelet therapy (1-3 months) can be considered, with subsequent transition to P2Y12 inhibitor monotherapy to reduce the risk of bleeding events.[2][97]

Abbreviated dual antiplatelet therapy strategies and de-escalation of dual antiplatelet therapy can be considered in patients at high risk of bleeding.[5]

Primary options

aspirin-tolerant

aspirin: 81 mg orally once daily

-- AND --

clopidogrel: 75 mg orally once daily

or

ticagrelor: 90 mg orally twice daily

or

prasugrel: 10 mg orally once daily

OR

aspirin-intolerant

clopidogrel: 75 mg orally once daily

or

ticagrelor: 90 mg orally twice daily

or

prasugrel: 10 mg orally once daily

Plus – continue beta-blocker

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ONGOING
|
post-stabilization
Plus – 

continue beta-blocker

Treatment recommended for ALL patients in selected patient group

Indefinite use of oral beta-blockers has been shown to benefit patients with acute infarction and/or reduced left ventricular function.

Cardioselective beta-blockers are preferred in the initial management of non-ST-elevation myocardial infarction (NSTEMI), but guidelines recommend metoprolol, bisoprolol, or carvedilol for post-NSTEMI management in patients with stabilized heart failure and reduced systolic function.[88]​​[97]​ The decision to continue beta-blockers long term after revascularization should be made on an individualized basis.[97]

Primary options

metoprolol succinate: 25-200 mg orally (extended-release) once daily

OR

bisoprolol: 1.25 to 10 mg orally once daily

OR

carvedilol: 12.5 mg orally twice daily for 2 days, followed by 25 mg twice daily

Plus – statin

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ONGOING
|
post-stabilization
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

All patients with non-ST-elevation myocardial infarction should receive a high-intensity statin (moderate intensity if not candidate for high-intensity) in hospital regardless of cholesterol levels, and if there are no contraindications.[5][163][164]​​​ A high-intensity statin is defined as a daily dose that lowers low-density lipoprotein cholesterol (LDL-C) by approximately >50%, while a moderate-intensity statin daily dose lowers LDL-C by approximately 30% to 50%.

Statins inhibit the rate-limiting step in cholesterol synthesis. They may also reduce vascular inflammation, improve endothelial function, and decrease thrombus formation in addition to lowering LDL.[167]

For secondary prevention, treatment of patients who have atherosclerotic cardiovascular disease (ASCVD) depends on their risk of future ASCVD events.[163] 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 coronary intervention, diabetes mellitus, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-C [≥100 mg/dL] 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. In patients not at very high risk of future events, high-intensity statin therapy should be initiated and continued in those ages up to 75 years with the aim of achieving a 50% or greater reduction in LDL-C levels. Moderate-intensity statin therapy may be used (reducing LDL-C 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.[163]​ All patients should have a fasting lipid panel 4-8 weeks after statin initiation or dose adjustment of lipid-lowering therapy to assess both patient lipid level response and/or adherence to therapy.[2]

Patients should be monitored for jaundice, malaise, fatigue, and lethargy.[168]

Fractionated bilirubin should be used rather than alanine aminotransferase (ALT) or aspartate transaminase (AST) to detect liver dysfunction. If evidence of liver injury is found, the statin should be stopped. If ALT or AST exceeds 3 times the upper limit of normal, the levels can be repeated but there is no need to stop the statin.[168]

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

lovastatin: 40 mg orally 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

simvastatin: 20-40 mg orally once daily

More

OR

moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

moderate-intensity statin

pitavastatin: 2-4 mg orally once daily

Consider – ezetimibe

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ONGOING
|
post-stabilization
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

For patients at very high risk of future events, and those ages up to 75 years and not at very high risk, ezetimibe may be added if the patient is on maximal statin therapy and LDL-cholesterol levels suggest targets will not be met with statin therapy alone.[5]​​[52][163]​​[169]

It is reasonable in this high-risk population to further intensify lipid-lowering therapy with a non-statin agent, such as ezetimibe, if the LDL-C level is 55 to <70 mg/dL (1.4 to <1.8 mmol/L) and the patient is already on a maximally tolerated statin. The LDL-C lowering potential of ezetimibe is greatest when used in combination with a statin.[2]

Primary options

ezetimibe: 10 mg orally once daily

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

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ONGOING
|
post-stabilization
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

The addition of a PCSK9 inhibitor monoclonal antibody such as alirocumab and evolocumab to maximally tolerated statin and ezetimibe therapy may also be considered for patients at very high risk of future events if LDL-cholesterol level remains ≥70 mg/dL or non-HDL-cholesterol ≥100 mg/dL.[5][163]​​[171][172][173]​ 

Alirocumab is approved for use as adjunct therapy to diet and maximally tolerated statin therapy for adult patients with heterozygous familial hypercholesterolemia, or with clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL and also to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.

Evolocumab is approved as an adjunct to diet and other lipid-lowering therapies (e.g., statins, ezetimibe) in patients with primary hyperlipidemia (including heterozygous hypercholesterolemia) and homozygous familial hypercholesterolemia to reduce LDL. It is now also approved to reduce the risk of myocardial infarction in patients with established cardiovascular disease, and may be used for this indication without adjunctive diet and lipid-lowering therapies.

Evolocumab and alirocumab may also be used as an alternative to statins if they are contraindicated or the patient is intolerant of statins.

Primary options

alirocumab: 75-150 mg subcutaneously once every two weeks, or 300 mg subcutaneously once monthly

OR

evolocumab: 140 mg subcutaneously once every two weeks, or 420 mg subcutaneously once monthly

Consider – ACE inhibitor or angiotensin-II receptor antagonist

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ONGOING
|
post-stabilization
Consider – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for SOME patients in selected patient group

ACE inhibitors should be used in all patients with left ventricle systolic dysfunction with reduced ejection fraction (<40%), hypertension, diabetes, and/or stable chronic kidney disease.[2][5]​​​​[176][189]​​ 

Angiotensin-II receptor antagonists may be used in cases of intolerance to ACE inhibitors.[178][179][180]

ACE inhibitors or angiotensin-II receptor antagonists may be started 24 hours post myocardial infarction.

Goal BP is at least <140/90 mmHg (including patients with chronic kidney disease or diabetes).[177]

Primary options

enalapril: 2.5 mg orally once daily for 48 hours, increase gradually to 10 mg twice daily

OR

lisinopril: 5 mg orally once daily for 48 hours, followed by 5-10 mg once daily

OR

captopril: 6.25 mg orally three times daily starting on day 3 post-MI, increase gradually to 50 mg three times daily

Secondary options

valsartan: 20 mg orally twice daily initially, increase gradually to 160 mg twice daily

OR

losartan: 50 mg orally once daily initially, increase gradually to 100 mg once daily

OR

candesartan cilexetil: 4 mg orally once daily initially, increase gradually to 32 mg once daily

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

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ONGOING
|
post-stabilization
Consider – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for SOME patients in selected patient group

An SGLT2 inhibitor (e.g., dapagliflozin, empagliflozin) should be given to patients with heart failure when they are clinically stable, regardless of their left ventricular ejection fraction.[190][191]​​[192]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

Consider – aldosterone antagonist

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ONGOING
|
post-stabilization
Consider – 

aldosterone antagonist

Treatment recommended for SOME patients in selected patient group

Aldosterone antagonists (e.g., eplerenone, spironolactone) should be used in all patients with left ventricular dysfunction (ejection fraction ≤40%), a history of diabetes mellitus, or evidence of congestive heart failure (S3 gallop, rales). They should be started in patients receiving target doses of an ACE inhibitor or angiotensin-II receptor antagonist. Aldosterone blockade should not be used in patients with serum creatinine >2.5mg/dL in men or >2.0mg/dL in women, as well as in patients with hyperkalemia (potassium >5.0mEq/L).[181]

Primary options

eplerenone: 25 mg orally once daily initially, increase gradually to 50 mg once daily within 4 weeks

OR

spironolactone: 12.5 to 25 mg orally once daily

Consider – anticoagulation

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ONGOING
|
post-stabilization
Consider – 

anticoagulation

Treatment recommended for SOME patients in selected patient group

Oral anticoagulation may be indicated at discharge in selected patients with non-ST-elevation myocardial infarction who are considered to be at high-risk for recurrent thrombosis (e.g., patients with atrial fibrillation, venous thromboembolism, prosthetic heart valve). While direct thrombin and factor Xa inhibitors may produce a modest reduction in ischemic events when added to antiplatelet therapy, results also suggest that they increase the risk of major bleeding, particularly when added to dual antiplatelet therapy with aspirin and clopidogrel.[182]​ Low-dose rivaroxaban has been demonstrated to reduce future cardiovascular events but causes an almost equivalent increase in major bleeding events.[183][184]​​​​​ 

In patients requiring continued oral anticoagulation, aspirin should be discontinued after 1-4 weeks of triple antithrombotic therapy, with continued use of a P2Y12 inhibitor (preferably clopidogrel) and an oral anticoagulant to reduce bleeding risk.[2]

Primary options

warfarin: consult specialist for guidance on dose

OR

rivaroxaban: consult specialist for guidance on dose

OR

apixaban: consult specialist for guidance on dose

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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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