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

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all patients

1st line – education and lifestyle modification

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all patients
1st line – 

education and lifestyle modification

All patients should be provided with individualized patient education and guideline-directed medical therapy with the goals of reducing the risk of future cardiovascular events and reducing anginal symptoms.

Patient education includes ongoing assessments and recommendations to help patients achieve weight management, increased physical activity, dietary modifications, lipid goals, and smoking cessation.[23][26]​​​​ [ Cochrane Clinical Answers logo ] [Evidence C]​ Cardiac rehabilitation, a multidisciplinary approach that combines assessment, education, assistance with lifestyle modification, psychosocial support, and supervised exercise is recommended after myocardial infarction (MI) and revascularization as well as for patients with stable angina.[23][26]​​[137] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

Additionally, helping patients understand their medication regimens is a key component of patient education and medication adherence.[26]​​

Plus – antiplatelet ± anticoagulant therapy

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all patients
Plus – 

antiplatelet ± anticoagulant therapy

Treatment recommended for ALL patients in selected patient group

All patients should be started on aspirin and this should be continued indefinitely. For patients with a contraindication to aspirin therapy, it is reasonable to use clopidogrel.[23][26]​​​[162][231][232]

After an episode of acute coronary syndrome or placement of cardiac stents, combination therapy with aspirin plus a P2Y12 inhibitor is indicated. Duration of dual therapy depends on the bleeding risk and antithrombotic benefit; minimum durations are particularly important to prevent thrombosis within cardiac stents.

For selected patients who are at high-risk of ischemic events and low-risk of bleeding who do not have a separate indication for anticoagulation, the addition of low-dose rivaroxaban to aspirin monotherapy can reduce a combined cardiovascular outcome. The benefit is primarily reduced stroke and peripheral arterial disease rather than MI and comes at the cost of increased bleeding.[26][168]

Primary options

aspirin: 75-100 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

OR

aspirin: 75-100 mg orally once daily

and

clopidogrel: 75 mg orally once daily

OR

aspirin: 75-100 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

Plus – high-intensity statin

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all patients
Plus – 

high-intensity statin

Treatment recommended for ALL patients in selected patient group

High-intensity statins are the mainstay of lipid pharmacotherapy and appropriate for all patients with chronic coronary disease (unless clearly contraindicated), regardless of baseline low-density lipoprotein.[26][63][99]​​​

Primary options

atorvastatin: high intensity: 40-80 mg orally once daily

OR

rosuvastatin: high intensity: 20-40 mg orally once daily

Consider – revascularization

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all patients
Consider – 

revascularization

Treatment recommended for SOME patients in selected patient group

Coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) is recommended to relieve anginal symptoms in patients with continued unacceptable angina despite maximal medical therapy. Revascularization is also recommended in selected patients for whom it is thought to improve survival or other cardiac outcomes. This includes patients with significant stenosis of the left main coronary and, depending on the guideline, patients with other anatomy, reduced ejection fraction (EF) or large ischemic burden.[26]​​[210][212][213]

Some European guidelines suggest a less restrictive approach to revascularization of lesions that are functionally significant on invasive or noninvasive testing, although evidence for this approach is limited.[23] It is recommended that a multidisciplinary team of general cardiologists, interventional cardiologists, and cardiac surgeons - a "heart team" - assemble to discuss and make recommendations on the optimal management strategy. This may include guideline-directed medical therapy, PCI, CABG, or a combination of all three.

Revascularization does not obviate the need for aggressive risk-factor modification to reduce risk of future MI.

Plus – sublingual nitroglycerin

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all patients
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with anginal symptoms
Plus – 

sublingual nitroglycerin

Treatment recommended for ALL patients in selected patient group

Sublingual nitroglycerin is the preferred therapy to terminate acute episodes of angina or for prophylaxis before activities known to induce anginal symptoms.

The mechanism of action is to reduce left ventricular wall stress and associated myocardial oxygen demand through systemic vasodilation. Coronary blood flow is also increased by coronary vasodilation. Onset of action is within minutes.[233]

Failure to resolve anginal symptoms with a reduction in physical activity and a trial of sublingual nitroglycerin should prompt emergency evaluation for an ACS (unstable angina or MI).[23]​​

Concurrent use of phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, or vardenafil) is contraindicated as the combination may result in a precipitous drop in blood pressure (BP).[26]

Primary options

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

Plus – beta-blocker ± calcium-channel blocker ± long-acting nitrate

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all patients
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with anginal symptoms
Plus – 

beta-blocker ± calcium-channel blocker ± long-acting nitrate

Treatment recommended for ALL patients in selected patient group

Primary therapies for patients with chronic anginal symptoms may include beta-blockers (e.g., metoprolol, nadolol, bisoprolol), calcium-channel blockers (e.g., nifedipine, amlodipine), and long-acting nitrates.

Guidelines generally recommend either a beta-blocker or a calcium-channel blocker first-line; choice of agent may be affected by the patient's baseline pulse, BP, and comorbidities including systolic dysfunction.[23][26]​​​[210]

Primary options

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

or

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

or

nadolol: 40-80 mg orally once daily

or

bisoprolol: 5-20 mg orally once daily

-- AND / OR --

nifedipine: 30-90 mg orally (extended-release) once daily

or

amlodipine: 5-10 mg orally once daily

-- AND / OR --

isosorbide mononitrate: 20 mg orally (immediate-release) twice daily

or

isosorbide dinitrate: 5-40 mg orally (immediate-release) two to three times daily

or

nitroglycerin transdermal: 0.2 to 0.8 mg/hour for 12 hours once daily, with a patch-free interval of 12 hours each day

Consider – other antianginal therapies

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all patients
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with anginal symptoms
Consider – 

other antianginal therapies

Treatment recommended for SOME patients in selected patient group

Other antianginal therapies, such as ranolazine, may be considered for angina that persists despite use of primary therapies.

Primary options

ranolazine: 500-1000 mg orally twice daily

Consider – antihypertensive therapy

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all patients
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with hypertension
Consider – 

antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

The US guidelines now recommend that patients with CCD and hypertension be treated to a target below 130/80 mmHg.[190]​ European guidelines recommend 120-130 mmHg systolic for most patients with CCD and 130-140 mmHg for those over 65 years old.[23]

Beta-blockers and ACE inhibitors or angiotensin-II receptor antagonists are indicated regardless of BP for some CCD patients (i.e., those with LVD, MI in the past 3 years, or stable angina) and these agents may also be considered as treatments for hypertension in other patients with CCD, although beta-blockers are generally less potent and therefore less preferred in the absence of another indication.[26]

Calcium-channel blockers also have antianginal properties and may be used in conjunction with beta-blockers. Additional medications, including diuretics, may be required to achieve BP targets.

Atenolol and beta-blockers with intrinsic sympathomimetic activity are inferior to other beta-blockers, especially in older patients. Consider alternatives to atenolol, labetalol, acebutolol, or pindolol. Lifestyle modification, including physical activity, the Dietary Approach to Stop Hypertension (DASH) or mediterranean diet pattern, reduced dietary sodium and alcohol, and weight reduction, is recommended for patients with CCD and elevated BP (120 to 129/<80mmHg).[190][191]

Primary options

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

or

metoprolol succinate: 50-200 mg orally (extended-release) once daily

or

nadolol: 40-120 mg orally once daily

or

bisoprolol: 2.5 to 10 mg orally once daily

or

carvedilol: 6.25 to 25 mg orally (immediate-release) twice daily; 20-80 mg orally (extended-release) once daily

-- AND / OR --

benazepril: 10-40 mg/day orally given in 1-2 divided doses

or

captopril: 12.5 to 150 mg/day orally given in 2-3 divided doses

or

enalapril: 5-40 mg/day orally given in 1-2 divided doses

or

fosinopril: 10-40 mg orally once daily

or

lisinopril: 10-40 mg orally once daily

or

perindopril erbumine: 4-16 mg/day orally given in 1-2 divided doses

or

quinapril: 10-80 mg/day orally given in 1-2 divided doses

or

ramipril: 2.5 to 20 mg/day orally given in 1-2 divided doses

or

trandolapril: 1-4 mg orally once daily

or

losartan: 50-100 mg/day orally given in 1-2 divided doses

or

telmisartan: 20-80 mg orally once daily

or

olmesartan medoxomil: 20-40 mg orally once daily

or

azilsartan medoxomil: 40-80 mg orally once daily

Consider – additional lipid-lowering therapy

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all patients
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with persistently elevated LDL-C and/or fasting triglyceride level despite maximally-tolerated statin
Consider – 

additional lipid-lowering therapy

Treatment recommended for SOME patients in selected patient group

The evidence supporting statin therapy in CCD far exceeds that of other lipid-lowering medications. However, for patients unable to take statins, or who have a less than expected reduction in low-density lipoprotein (LDL) despite adherence at the highest tolerated dose, ezetimibe monotherapy or combination therapy with ezetimibe and a statin may be considered.[26][44]

For patients at very high risk with persisting elevations in LDL, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor (e.g., alirocumab, evolocumab) may be added (although cost may remain a barrier).

Newer nonstatin therapies are approved (e.g., bempedoic acid, inclisiran); however, evidence-based guidelines do not recommend their use as yet, and you should consult your local protocols.[173]​ See Emerging treatments.

In patients with a persistent high fasting triglyceride level (150 to 499 mg/dL [1.7 to 5.6 mmol/L]) after modification of lifestyle factors and management of LDL, the US guidelines suggest a possible role for icosapent ethyl.[26]

The decision to add nonstatin therapies should be shared between patient and clinician following a discussion on the risks and benefits, and taking into account patient preferences. Lifestyle modifications should be optimized, in addition to reviewing adherence to statins.

Primary options

ezetimibe: 10 mg orally once daily

Secondary 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

OR

icosapent ethyl: 2 g orally twice daily

Plus – sodium-glucose transporter-2 (SGLT2) inhibitor and/or glucagon-like peptide-1 (GLP-1) receptor agonist

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all patients
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with type 2 diabetes
Plus – 

sodium-glucose transporter-2 (SGLT2) inhibitor and/or glucagon-like peptide-1 (GLP-1) receptor agonist

Treatment recommended for ALL patients in selected patient group

For patients with CCD and type 2 diabetes, use of either a SGLT2 inhibitor (e.g., empagliflozin, dapagliflozin, canagliflozin) or a GLP-1 receptor agonist (e.g., liraglutide, dulaglutide) is recommended independent of A1c.[26][198]

Both SGLT2 inhibitors and GLP-1 receptor agonists have shown significant cardiovascular benefits beyond their effects on glycemia.[40][193][194][195][196][197]

Use of both an SGLT2 inhibitor and a GLP-1 receptor agonist may be considered when needed for additional glycemic control but the additional cardiovascular benefits of the combination have not been defined.

Primary options

empagliflozin: 10-25 mg orally once daily

or

dapagliflozin: 10 mg orally once daily

or

canagliflozin: 100-300 mg orally once daily

-- AND / OR --

liraglutide: 0.6 to 1.8 mg subcutaneously once daily

or

dulaglutide: 0.75 to 4.5 mg subcutaneously once weekly

Plus – ACE inhibitor or angiotensin-II receptor antagonist

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all patients
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with type 2 diabetes
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

ACE inhibitors (or angiotensin-II receptor antagonists) are recommended in the US and European guidelines for patients with CCD and diabetes mellitus to reduce risk of cardiovascular events.[23][26]

Primary options

benazepril: 10-40 mg/day orally given in 1-2 divided doses

OR

captopril: 12.5 to 150 mg/day orally given in 2-3 divided doses

OR

enalapril: 5-40 mg/day orally given in 1-2 divided doses

OR

fosinopril: 10-40 mg orally once daily

OR

lisinopril: 10-40 mg orally once daily

OR

perindopril erbumine: 4-16 mg/day orally given in 1-2 divided doses

OR

quinapril: 10-80 mg/day orally given in 1-2 divided doses

OR

ramipril: 2.5 to 20 mg/day orally given in 1-2 divided doses

OR

trandolapril: 1-4 mg orally once daily

OR

losartan: 50-100 mg/day orally given in 1-2 divided doses

OR

telmisartan: 20-80 mg orally once daily

OR

olmesartan medoxomil: 20-40 mg orally once daily

OR

azilsartan medoxomil: 40-80 mg orally once daily

Plus – ACE inhibitor or angiotensin-II receptor antagonist

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all patients
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with chronic kidney disease (CKD)
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

ACE inhibitors (or angiotensin-II receptor antagonists) are recommended in the US and European guidelines for patients with CCD and CKD to reduce risk of cardiovascular events.[23][26]​ Choice of drug and the appropriate dose depends on the severity of renal impairment, and you should consult your local drug information source or a specialist for further guidance.

Consider – weight loss program (pharmacologic therapy or bariatric surgery)

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all patients
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with obesity
Consider – 

weight loss program (pharmacologic therapy or bariatric surgery)

Treatment recommended for SOME patients in selected patient group

For those with overweight or obesity, counseling on weight loss, with goals including reducing body weight with diet and physical activity, is advised.[23][26]​ Guidelines further advise consideration of pharmacologic therapy and bariatric surgery in selected patients.[26]

Although weight loss interventions improve cardiovascular risk factors (including weight, BP, lipids, insulin resistance) there is limited evidence of improved cardiovascular outcomes in weight loss trials.[48]​ Given the imperfections of body mass index as a risk marker, the limited efficacy of even multicomponent lifestyle interventions in promoting sustained weight loss, and concern for weight stigma as a barrier to care, providers might also focus on physical activity and cardiorespiratory fitness rather than weight per se as a treatment goal.

See Obesity in adults.

Plus – guideline-directed management and therapy

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all patients
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with heart failure (HF)
Plus – 

guideline-directed management and therapy

Treatment recommended for ALL patients in selected patient group

Patients with CCD and HF with reduced EF or HF with preserved EF should receive treatment as per current HF guidelines.[229][230]

In selected patients with coronary artery disease and HF with left ventricular EF ≤35% and suitable coronary anatomy, surgical revascularization in addition to GDMT for HF may improve symptoms, cardiovascular hospitalizations, and long-term all-cause mortality.[26][229][230]

See Heart failure with reduced ejection fraction, and Heart failure with preserved ejection fraction.

Plus – anticoagulant therapy

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all patients
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with atrial fibrillation (AF)
Plus – 

anticoagulant therapy

Treatment recommended for ALL patients in selected patient group

In patients with CCD and AF, long-term anticoagulant therapy is recommended for reduction of ischemic stroke and other ischemic events.[23]​ Oral anticoagulant monotherapy (preferably with a direct oral anticoagulant [DOAC]) without antiplatelet is recommended for many patients with stable CCD.[23][26]​ For select patients at higher risk (either chronically or temporarily following an event or procedure) combination of a DOAC and single antiplatelet agent may be appropriate.

Use of triple therapy (a DOAC plus dual antiplatelet therapy [DAPT]) confers a very high bleeding risk but may be indicated for up to 1 month after PCI, followed by a single antiplatelet agent plus a DOAC for 6-12 months.[26]​

See Established atrial fibrillation.

Consider – psychologic and pharmacologic interventions

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all patients
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with depression
Consider – 

psychologic and pharmacologic interventions

Treatment recommended for SOME patients in selected patient group

Depression is common in patients with CCD, particularly after acute infarction. It is associated with worse health behaviors and possibly worse cardiovascular outcomes.[149]​ Evidence on the cardiac effects of depression treatment is limited, but it is reasonable to screen patients and treat as indicated.[23][26][150]

See Depression in adults.

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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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