Chronic Coronary Syndromes Management

The first step in the management of patients suspected of chronic coronary syndromes is a general clinical evaluation focusing on assessment of signs and symptoms of chronic coronary syndromes, differentiating non-cardiac causes of chest pain and excluding acute coronary syndrome.  

Rule Out Unstable Angina 

Unstable angina is defined as angina of new onset, increases in frequency, intensity or duration, or occurring at rest. The presence of unstable angina predicts a higher short-term risk of acute coronary event. Moderate- to high-risk patients should be promptly evaluated and treated in the emergency department because of the higher risk of coronary artery plaque rupture and death. Low-risk patients are comparable to those patients with stable angina and their evaluation can be performed safely and expeditiously in an outpatient setting.  

Please see Acute Coronary Syndromes without Persistent ST-Segment Elevation disease management chart for further information. 

In patients with stable chest pain, it is recommended to optimize guideline-directed medical therapy in those with obstructive coronary artery disease and to optimize preventive therapies in those with non-obstructive coronary artery disease. The optimization of a guideline-directed medical therapy is recommended in patients with chronic coronary syndromes to reduce major adverse cardiovascular events. Both antianginal therapy and treatment to reduce the incidence of adverse cardiac events should be administered. The selection of treatment should consider the patient’s preferences and expectations, costs and possible complications from medications or procedures. Routine assessment for social determinants of health including assessment of mental health, psychosocial stressors, health literacy, sociocultural influences, financial strain, transportation, insurance status, barriers to adherence to a heart healthy diet, neighborhood or environmental exposures, viable options for regular physical activity and social support, is recommended for patient-centered treatment decisions and lifestyle change recommendations.  

The goals of therapy for chronic coronary syndromes are to relieve anginal symptoms and reduce ischemia; improve chest pain-free exertion capacity; reduce atherosclerosis progression; prevent subsequent acute myocardial infarction (AMI), unstable angina and cardiac death; and improve quality of life and life expectancy. 

RISK FACTOR MODIFICATION  

Treat Dyslipidemia  

The goals in treating dyslipidemia are: Low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL (<1.4 mmol/L) and ≥50% LDL-C reduction from baseline in very high-risk patients (patients with established ASCVD); for patients with ASCVD who had a second vascular event within 2 years (not necessarily of the same type as the first) while on maximally tolerated statin-based therapy, an even lower low-density lipoprotein cholesterol target level of <40 mg/dL (<1.0 mmol/L) may be considered; high-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL (≥1.6 mmol/L) (negative risk factor); and triglyceride (TG) <150 mg/dL (<1.7 mmol/L). Assess the fasting lipid profile in all patients and within 24 hours of hospitalization for those patients who present with an acute event if not previously done. Lifestyle modifications which include daily physical activity and weight management are strongly recommended for all ischemic heart disease patients. It is recommended to add plant stanol/sterols at 2 g/day and/or viscous fiber >10 g/day to further lower low-density lipoprotein cholesterol.  







High-dose statin therapy that results in ≥50% reduction in low-density lipoprotein cholesterol levels is recommended in the absence of contraindications or adverse effects in addition to lifestyle modifications. Consider combination with Ezetimibe if target goals are not achieved with a maximally tolerated dose of statin. An addition of Bempedoic acid is recommended in chronic coronary syndromes patients who are statin-intolerant and when targets are not achieved on Ezetimibe. An addition of Bempedoic acid may be considered in chronic coronary syndromes patients when targets are not achieved with a maximally tolerated dose of statin and Ezetimibe. Consider combination with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for very high-risk patients who did not achieve target goals on maximally tolerated dose of statin and Ezetimibe combination therapy. An addition of Bempedoic acid or Inclisiran instead of PCSK9 inhibitor should be considered in chronic coronary syndrome patients with a maximally tolerated statin dose who have low-density lipoprotein cholesterol level ≥70 mg/dl (≥1.8 mmol/L) and in whom Ezetimibe and PCSK9 inhibitor are not tolerated or insufficient. The use of moderate-intensity statins is recommended in patients with intolerance or contraindications to high-intensity statins with the aim of achieving a 30-49% reduction in low-density lipoprotein cholesterol levels to reduce the risk of major adverse cardiovascular events. High-dose statins reduce major vascular events by 15% compared to moderate-dose statins irrespective of the age of the patient.  

Bile acid sequestrants, Niacin or Ezetimibe are alternative agents for patients who cannot tolerate statins. Therapy can be started soon after admission and continued on discharge if the patient has been hospitalized. In patients with TG ≥500 mg/dL (≥13 mmol/L), Niacin or fibrate should be initiated before low-density lipoprotein cholesterol-lowering therapy. Icosapent ethyl may be considered in chronic coronary syndrome patients on a maximally tolerated statin dose with LDL-C <100 mg/dL (<2.6 mmol/L) and a persistent fasting TG level of 150-499 mg/dL (1.7-5.6 mmol/L) after identifying and managing secondary causes to reduce the risk of major adverse cardiovascular events and cardiovascular death.  

Please see Dyslipidemia disease management chart for further information. 

Treat Hypertension  

The goal is a blood pressure of <130/80 mmHg in patients with uncomplicated hypertension, diabetes mellitus and chronic renal disease*. Blood pressure monitoring and lifestyle modification are recommended in all patients with ischemic heart disease.   

Antihypertensive therapy should be initiated in addition to or after a trial of lifestyle modifications. The choice of antihypertensive drugs is based on patient characteristics, indications for specific classes of drugs and comorbid illnesses. It may include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and/ or beta-blockers, with addition of other drugs such as thiazide diuretics or calcium channel blockers if necessary to achieve optimal blood pressure control. It is recommended to give beta-blockers and renin-angiotensin system blockers to post-MI hypertensive patients and beta-blockers and/or calcium channel blockers to patients with symptomatic angina. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should always be included because of the renal protective effects.

*Recommendations for blood pressure goals may vary between countries. Please refer to available guidelines from local health authorities.  

Please see Hypertension disease management chart for further information. 

Treat Diabetes Mellitus (DM)  

The goal in the treatment of diabetes mellitus should be individualized. For most adults, the recommended HbA1c goal is <7%. Diabetes management includes lifestyle modification and pharmacological therapy to achieve the target HbA1c.   

For patients with diabetes mellitus and cardiovascular disease, sodium-glucose linked transporter/co-transporter 2 (SGLT2) inhibitors and GLP-1 receptor agonists are recommended. Sodium-glucose linked transporter/co-transporter 2 inhibitors are also recommended for chronic coronary syndrome patients with heart failure (LVEF ≤40%) with or without diabetes to reduce the risk of cardiovascular death and heart failure hospitalization and improve quality of life. Treatment of other modifiable risk factors that accompany diabetes mellitus, such as hypertension and dyslipidemia results in a substantial decrease in cardiovascular risk.  

Please see Diabetes Mellitus disease management chart for further information.

REDUCTION OF INCIDENCE OF ADVERSE CARDIAC EVENTS  

Antiplatelet Agents  

Continuity of antiplatelet therapy after bleeding during treatment should be based on the bleeding severity and the proximity of the bleeding episode to the index ischemic event or percutaneous coronary intervention. To minimize ischemic risk, continue antiplatelet therapy if bleeding is within 1 month of the index event. Consider reducing the dose of antiplatelet, changing to less potent antiplatelets or using 1 antiplatelet agent in patients with bleeding who need de-escalation of antiplatelet therapy. Dual antiplatelet therapy (DAPT) consisting of Aspirin 75-100 mg and Clopidogrel 75 mg daily for up to 6 months is recommended as the default antithrombotic strategy after PCI-stenting in chronic coronary syndrome patients without indication for oral anticoagulation. Discontinuation of dual antiplatelet therapy 1-3 months after percutaneous coronary intervention and continuation with single antiplatelet therapy (SAPT) is recommended in patients with high bleeding risk but without high ischemic risk. Discontinuation of dual antiplatelet therapy after 1-3 months from percutaneous coronary intervention-stenting may be considered in patients without high bleeding risk and high risk of ischemic events. In chronic coronary syndromes patients after uncomplicated percutaneous coronary intervention and with concomitant indication of oral anticoagulant therapy, it is recommended to discontinue Aspirin in ≤1 week, followed by continuation of oral anticoagulant therapy and Clopidogrel for up to 6 months in patients without high ischemic risk or for up to 12 months in patients with high ischemic risk, followed by oral anticoagulant therapy alone. In patients with high thrombotic risk or with anatomical/procedural characteristics outweighing bleeding risk, continuation of Aspirin up to 1 month after percutaneous coronary intervention in addition to oral anticoagulant therapy and Clopidogrel should be considered. In patients with chronic kidney disease and an eGFR 15 to <60 mL/min/1.73 m² transitioning to chronic coronary syndromes, dual antiplatelet therapy or dual platelet inhibition (DPI) may be given. In those with an eGFR <15 mL/min/1.73 m², consider giving single antiplatelet therapy after well-tolerated dual antiplatelet therapy of 3 months (post-PCI). In elderly patients transitioning to chronic coronary syndromes, extended dual antiplatelet therapy (if other risk factors are present) or DPI may be given to those >75-85 years old and not frail, while single antiplatelet therapy may be given to frail patients >75 years old or those >80 years old. A proton pump inhibitor should be considered when a single antiplatelet or anticoagulant agent is used. 

Aspirin

Chronic Coronary Syndromes_Management 2

Aspirin is an antiplatelet drug of choice due to cost-effectivity. Aspirin should be given indefinitely in patients with ischemic heart disease unless there are contraindications. This exerts an antithrombotic effect by irreversibly inhibiting prostaglandin synthetase action which prevents production of the platelet-aggregating substance thromboxane A2. This has been shown to be associated with a reduction in the risk of serious vascular events. Aspirin 75-100 mg/day is recommended in patients in sinus rhythm with a prior myocardial infarction or revascularization or after stenting. This is recommended lifelong in chronic coronary syndrome patients with history of myocardial infarction or remote percutaneous coronary intervention after an initial period of dual antiplatelet therapy. Aspirin is recommended lifelong in patients without a history of myocardial infarction or revascularization but with evidence of significant obstructive coronary artery disease. This is recommended lifelong in chronic coronary syndrome patients after coronary artery bypass graft and in chronic coronary syndrome patients without a history of myocardial infarction or revascularization but with evidence of significant obstructive coronary artery disease. It is recommended to initiate Aspirin after coronary artery bypass graft as soon as there is no concern for bleeding. Initial daily low dose of Aspirin in addition to oral anticoagulant therapy and Clopidogrel is recommended in patients with an indication for oral anticoagulation who will undergo percutaneous coronary intervention. Aspirin dose of 75-162 mg/day is equally as effective as 325 mg/day in secondary prevention and is associated with a lower risk of hemorrhage. The addition of a second antithrombotic agent to Aspirin for long-term secondary prevention in patients without high bleeding risk should be considered in those whose risk of ischemic events is high and may be considered in those whose risk of ischemic events is at least moderately increased. Use the lowest effective dose to optimize the balance between therapeutic benefits and gastrointestinal side effects during chronic therapy. A proton pump inhibitor may be used concomitantly if the risk of gastrointestinal bleeding is high.  

Clopidogrel  

Clopidogrel is used as an alternative drug if Aspirin is contraindicated or if the patient experiences serious adverse effects from Aspirin. This is recommended in chronic coronary syndrome patients with the history of myocardial infarction or percutaneous coronary intervention. This inhibits platelet aggregation via selective and irreversible inhibition of adenosine diphosphate receptor. In addition to Aspirin, Clopidogrel (after an appropriate loading dose) may be given for 6 months after coronary stenting to patients in sinus rhythm, unless the risk or occurrence of life-threatening bleeding warrants a shorter course (1-3 months). A study showed that Clopidogrel demonstrated superiority over Aspirin in the secondary prevention of myocardial infarction and death in patients with previous myocardial infarction, stroke or symptomatic peripheral artery disease. However, the difference was small and no other trials have been conducted in patients with stable ischemic heart disease. Thus, Clopidogrel remains an acceptable alternative drug to Aspirin.  

Prasugrel  

Prasugrel may be considered instead of Clopidogrel for the first month and up to 3-6 months in chronic coronary syndrome patients undergoing high-thrombotic risk stenting (eg complex left main stem, 2-stent bifurcation, suboptimal stenting result, prior stent thrombosis, previously known CYP2C19*2/*3 polymorphisms). 

Ticagrelor  

Ticagrelor monotherapy may be considered as an alternative to dual antiplatelet therapy or other single antiplatelet therapy in chronic coronary syndrome patients or stabilized post-ACS patients who underwent percutaneous coronary intervention and were initially treated with Ticagrelor-based dual antiplatelet therapy and remain at high ischemic risk and without high bleeding risk. This may be considered instead of Clopidogrel for the first month and up to 3-6 months in chronic coronary syndrome patients undergoing high-thrombotic risk stenting (eg complex left main stem, 2-stent bifurcation, suboptimal stenting result, prior stent thrombosis, previously known CYP2C19*2/*3 polymorphisms).  

Vorapaxar  

Vorapaxar may be added to Aspirin in chronic coronary syndrome patients with a previous history of myocardial infarction without a history of stroke, transient ischemic attacks or intracranial hemorrhage to reduce major adverse cardiovascular events. This selectively inhibits PAR-1, a key receptor for thrombin activation, leading to inhibition of thrombin-induced platelet aggregation. 

Anticoagulants  

Direct Oral Anticoagulant (DOAC) 

Direct oral anticoagulant is recommended for chronic coronary syndrome patients who underwent elective percutaneous coronary intervention and require oral anticoagulant therapy in addition to dual antiplatelet therapy for 1-4 weeks, followed by Clopidogrel alone for 6 months. This is recommended in preference to vitamin K antagonist in patients who are eligible for oral anticoagulation therapy. In atrial fibrillation, the therapeutic dose of direct oral anticoagulant (preferred) alone or vitamin K antagonist alone is recommended lifelong in chronic coronary syndrome patients with a long-term indication for oral anticoagulant therapy.  

Vitamin K Antagonist (VKA)  

In atrial fibrillation, a therapeutic dose of vitamin K antagonist alone or direct oral anticoagulant alone is recommended lifelong in chronic coronary syndromes patients with a long-term indication for oral anticoagulant therapy. 

Lipid-lowering Agents  

Lipid-lowering agents have shown that a decrease in low-density lipoprotein cholesterol is associated with reduced risk of adverse cardiovascular events. Studies showed a decrease in chest pain and the need for revascularization in patients with stable coronary artery disease.  

Statins  

Example drugs: Atorvastatin, Rosuvastatin, Simvastatin  

Statins are recommended in all patients with chronic coronary syndromes. This is a first-line treatment for patients with chronic coronary syndromes and dyslipidemia. High-intensity statin up to the highest tolerated dose is recommended in all patients with chronic coronary syndromes to reach low-density lipoprotein cholesterol goals. This is effective in the primary and secondary prevention of coronary events and lipid management. Other agents that may be added to statins to achieve low-density lipoprotein cholesterol targets include Ezetimibe, PCSK9 inhibitors, Bempedoic acid and Inclisiran.  

Please see Dyslipidemia disease management chart for further information. 

Angiotensin-Converting Enzyme (ACE) Inhibitors 







Angiotensin-converting enzyme (ACE) inhibitors are recommended in all patients with chronic coronary syndromes who also have hypertension, diabetes mellitus, LVEF of ≤40% (symptomatic heart failure or asymptomatic left ventricular dysfunction after myocardial infarction) or chronic renal disease unless contraindicated, and should be considered in patients at very high risk of cardiovascular adverse events. These reduce angiotensin II with an increase in bradykinin which decreases left ventricular and vascular hypertrophy, atherosclerosis progression, plaque rupture and thrombosis. Aldosterone blockade with Spironolactone or Eplerenone is recommended for use in post-myocardial infarction patients without significant renal dysfunction or hyperkalemia, those who are already receiving therapeutic doses of an angiotensin-converting enzyme inhibitor and a beta-blocker, have an LVEF ≤35% and have either diabetes or heart failure. Consider giving an angiotensin receptor-neprilysin inhibitor (as a replacement to an angiotensin-converting enzyme inhibitor) to patients with an LVEF ≤35% who are still symptomatic despite optimal therapy with an angiotensin-converting enzyme inhibitor, a beta-blocker and a mineralocorticoid receptor antagonist (MRA). These exhibit cardiovascular protective effects by decreasing the risks of future ischemic events. Similar benefits are observed in patients with ischemic heart disease without left ventricular dysfunction. 

Angiotensin Receptor Blockers (ARBs)  

Angiotensin receptor blockers are recommended in patients with chronic coronary syndromes who have indications for, but are intolerant of, angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors. These bind competitively to the type 1 angiotensin II receptor which increases plasma renin activity, plasma renin and angiotensin I and II concentration. These have cardiovascular protection by decreasing blood pressure equivalent to those achieved by angiotensin-converting enzyme inhibitors and decrease left ventricular mass and stroke incidences compared with beta-blockers and improve outcomes in diabetic nephropathy and heart failure. In a combination study of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with coronary artery disease or diabetes mellitus plus additional risk factors with no evidence of congestive heart failure, it showed no increase in benefit and had more adverse effects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not prescribed together.  

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)  

Example drugs: Sacubitril/Valsartan  

Angiotensin receptor-neprilysin inhibitor is recommended as a replacement for angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in chronic coronary syndrome patients with heart failure with reduced EF (HFrEF) to reduce the risk of heart failure hospitalization and death. This may decrease myocardial ischemia by reducing left ventricular wall stress and improving coronary circulation. This has been shown to reduce heart failure hospitalization and cardiovascular death in patients with LVEF ≤35%. 

Beta-Blockers

Beta-blockers are recommended for chronic coronary syndrome patients with LVEF ≤40% with or without previous myocardial infarction to reduce the risk of major adverse cardiovascular events including cardiovascular death. Sustained-release Metoprolol succinate, Carvedilol or Bisoprolol with titration to target doses is preferred for chronic coronary syndrome patients with LVEF <50%. There is a decrease myocardial oxygen demand, improve ischemic threshold and prevent maladaptive left ventricular remodeling.  

Other Agents  

Colchicine  

Colchicine should be considered in chronic coronary syndrome patients with atherosclerotic coronary artery disease to reduce myocardial infarction, stroke and the need for revascularization. 

REDUCTION OF ISCHEMIA AND RELIEF OF SYMPTOMS  

Reducing cardiac ischemia symptoms and improving long-term survival are the main goals of antianginal therapy. Anti-ischemic therapy should be based on the patient’s blood pressure, heart rate, left ventricular function, comorbidities, concomitant medical therapy, adherence and preference. It is recommended to customize the selection of antianginal agents based on the patient’s characteristics, comorbidities, concomitant medications, treatment tolerability, underlying pathophysiology of angina, drug availability and cost. Beta-blockers and/or calcium channel blockers are initially indicated to control heart rate and symptoms. A beta-blocker, calcium channel blocker, or long-acting nitrate is recommended for relief of angina or equivalent symptoms in chronic coronary syndrome patients with angina. An addition of a second antianginal agent from a different therapeutic class (beta-blockers, calcium channel blockers, long-acting nitrates) is recommended for relief of angina or equivalent symptoms in chronic coronary syndromes patient with angina who remain symptomatic after initial therapy. Antianginal therapy should be used in conjunction with previously mentioned therapies to improve prognosis. Pharmacological therapy based on coronary functional test results in symptomatic patients with ANOCA/INOCA should be considered to improve symptoms and quality of life. Conditions that may provoke angina need to be investigated and treated appropriately. With appropriate treatment of these conditions, angina may resolve and further antianginal treatment may be unnecessary. If angina is improved but not completely resolved, further therapy should be initiated. 

Angiotensin-Converting Enzyme (ACE) Inhibitors  

Angiotensin-converting enzyme inhibitors should be considered for symptom control in patients with ANOCA/INOCA with endothelial dysfunction. 

Beta-Blockers 







Beta-blockers are the first-line treatment for patients with chronic coronary syndromes to control heart rate and symptoms. The goal if used as an antianginal agent is to lower resting heart rate to 55-60 beats per minute (bpm). These are recommended in all patients with left ventricular systolic dysfunction (LVEF ≤40%), with heart failure, high heart rate or prior myocardial infarction, unless there are contraindications. In patients with reduced left ventricular function, use should be limited to Carvedilol, Metoprolol succinate, Bisoprolol or Nebivolol which have shown to decrease the risk of death in stable optimally treated patients. These are started and continued for at least 1 year in all patients with normal left ventricular function after myocardial infarction or acute coronary syndrome. These should be considered for symptom control in patients with ANOCA/INOCA with microvascular angina associated with reduced coronary/myocardial blood flow reserve. Chronic beta-blocker therapy may be considered in all other patients with coronary or other vascular diseases. Long-term therapy with beta-blocker is not recommended to improve outcomes in chronic coronary syndrome patients without myocardial infarction in the past year, LVEF ≤50%, or another primary indication for therapy with beta-blocker. All beta-blockers appear to be equally effective in the treatment of angina.  

Beta-blockers inhibit catecholamines from binding to beta1, beta2 and beta3 receptors, which decrease myocardial oxygen consumption by reducing heart rate, atrioventricular nodal conduction, myocardial contractility and afterload. These attenuate cardiovascular remodeling by decreasing left ventricular wall tension with long-term use. The reduction in heart rate permits more diastolic time and greater coronary perfusion enhancing myocardial oxygen supply.  

Beta-blockers decrease angina onset with improvement in the ischemic threshold during exercise and episodes of angina. These improve survival and decrease recurrent myocardial infarction in patients with left ventricular dysfunction or a history of myocardial infarction. These are more effective than dihydropyridine calcium channel blockers in the control of angina, reduction of cardiovascular events and need for revascularization. These should be considered in combination with a calcium channel blocker when initial treatment with a calcium channel blocker alone is unsuccessful. Combination therapy of beta-blockers and dihydropyridine calcium channel blockers decrease dihydropyridine-induced tachycardia. These produce increased exercise time and capacity and lower the rate of cardiovascular events. Caution is necessary when beta-blocker is combined with Verapamil or Diltiazem because of possible bradycardia, AV block, or excessive fatigue. A combination therapy of beta-blocker and nitrate can be used in patients with stable ischemic heart disease. Nitrate increases sympathetic tone leading to reflex tachycardia which can be attenuated by the beta-blockers. Beta-blockers can increase left ventricular wall tension associated with reduced heart rate which is counteracted by the concomitant use of nitrate. This combination is more effective than either monotherapy in controlling angina. Patients with pure vasospastic angina (Prinzmetal angina) without fixed obstructive lesions should not use beta-blockers because they are ineffective and may increase the tendency to induce coronary vasospasm. Avoid abrupt withdrawal of beta-blockers because of the rebound phenomenon associated with increased risk for acute myocardial infarction and sudden death. Taper over 1- to 3-week period with the use of sublingual Nitroglycerin or substitution of a non-dihydropyridine calcium channel blocker. 

Calcium Channel Blockers  

Example drugs: dihydropyridines (eg Nifedipine, Amlodipine, Felodipine), non-dihydropyridines (eg Verapamil, Diltiazem)  

Calcium channel blockers are recommended in the following: As initial treatment for patients with chronic coronary syndromes to control heart rate or symptoms; for the relief of anginal symptoms in patients with chronic coronary syndromes when beta-blockers are contraindicated, have adverse effects or are unsuccessful; and to control symptoms and prevent ischemia and potentially fatal complications in patients with isolated vasospastic angina. This should be considered in combination with a beta-blocker when initial treatment with beta-blocker alone is unsuccessful. When used as monotherapy, Diltiazem is preferred because dihydropyridines can increase heart rate. Dihydropyridines are recommended as the first step in the management of chronic coronary syndromes in patients with low heart rate. This is a preferred calcium channel blockers for patients with Prinzmetal angina.  

Calcium channel blockers non-competitively limit calcium ion influx through voltage-dependent L-type calcium channels resulting in negative inotropic effects, cardiac pacemaker depression, slowing conduction and smooth muscle relaxation. These improve myocardial oxygen supply by reducing coronary vascular resistance and augmenting epicardial conduit vessel and systemic arterial blood flow. These decrease myocardial demand by decreasing myocardial contractility, systemic vascular resistance and arterial pressure.  

Calcium channel blockers decrease anginal episodes, increase exercise duration and reduce use of sublingual Nitroglycerin in patients with effort-induced angina.  

Avoid combination treatment with Verapamil or Diltiazem and beta-blockers because of possible adverse effects on AV nodal conduction, heart rate or cardiac contractility (ie symptomatic bradycardia). Non-dihydropyridines can depress left ventricular function and should not be used in chronic coronary syndrome patients with significant left ventricular dysfunction. 

Long-Acting Nitrates  

Long-acting nitrates are recommended for long-term relief of symptoms when initial therapy with a beta-blocker and/or non-dihydropyridine calcium channel blocker is contraindicated, poorly tolerated, causes undesirable side effects or inadequate in controlling angina symptoms. These should be considered in the following: To prevent recurrent episodes in patients with isolated vasospastic angina; and as an add-on therapy in patients with symptoms not adequately controlled with beta-blockers and/or calcium channel blockers or as part of initial treatment in properly selected patients. These are effective in the treatment and prevention of all forms of angina. These can also be used as monotherapy or in combination with beta-blockers in patients with Prinzmetal variant angina.  

Both coronary arteriolar and venous vasodilatation decrease myocardial oxygen demand by decreasing left ventricular volume and arterial pressure via preload reduction. These improve oxygen supply by their vasodilatory effects on epicardial arteries and collateral vessels. These have antithrombotic and antiplatelet effects.  

Long-acting nitrates improve exercise tolerance, time to ST-segment depression and time to onset of angina. These reduce the frequency and severity of angina attacks.   

Nitrates have an additive anti-ischemic effect when used in combination with beta-blockers or calcium channel blockers. Titration of the dose is important to have adequate control of angina with the lowest possible dose to limit the occurrence of headaches and hypotension, avoid nitrate tolerance, worsening of endothelial dysfunction and facilitate long-term adherence. Long-term use of nitrates may produce nitrate tolerance resulting in breakthrough angina. It is necessary to maintain a daily nitrate-free interval of 6-8 hours. Rebound angina may happen during this nitrate-free period. Nitrate tolerance does not develop with the sublingual route of administration and with long-acting nitrates via sublingual use. Strict avoidance of co-administration of phosphodiesterase inhibitors such as Avanafil, Sildenafil, Tadalafil or Vardenafil within 24-48 hours of nitrate administration because of the risk of profound hypotension. Abrupt discontinuation of nitrates can cause an increase in the severity of angina. Severity can be reduced by concomitant administration of other antianginal drugs or by tapering of the long-acting nitrate dosage. 

Short-Acting Nitrates  

Short-acting nitrates are recommended in all patients for immediate relief of acute symptoms and/or situational prophylaxis. Sublingual and oral spray Nitroglycerin immediately relieves exertional angina. Effective for prevention of effort-induced angina when administered 5-10 minutes before activity with relief lasting for 30-40 minutes.



 



Short-acting nitrates cause venodilatation and decreased diastolic filling of the heart (reduced intracardiac pressure) which promotes subendocardial perfusion. Coronary vasodilatation and coronary vasospasm antagonism.  

There is rapid and effective symptom relief achieved with sublingual/buccal tablets or oral spray.   

Appropriate instructions on how to use short-acting Nitroglycerin is important. Explain to the patient that it is a short-acting drug without any long-term effects and this may encourage use. Avoid nitrate tolerance because it blunts the response to short-acting Nitroglycerin. An attack of angina that does not respond to short-acting Nitroglycerin should be regarded as a possible myocardial infarction and immediate medical consultation is necessary. 

PATIENTS UNRESPONSIVE TO INITIAL THERAPY  

3-Ketoacyl-CoA Thiolase (3-KAT) Inhibitor  

Example drug: Trimetazidine (TMZ)  

3-Ketoacyl-CoA Thiolase (3-KAT) inhibitor is an effective antianginal therapy when used as monotherapy or in combination with other anti-ischemic agents. This may be considered as add-on therapy in patients with symptoms not adequately controlled with beta-blockers and/or calcium channel blockers or as part of initial treatment in properly selected patients.  

3-Ketoacyl-CoA Thiolase (3-KAT) inhibitor inhibits the 3-KAT enzyme in myocardial cells which optimizes cardiac metabolism by switching energy substrate preferences from fatty acid oxidation to glucose oxidation. This protects the myocardium from ischemic injury which limits myocyte loss during anginal episodes.  

3-Ketoacyl-CoA Thiolase (3-KAT) inhibitor increases coronary flow reserve which delays the onset of ischemia associated with exercise, improves functional capacity, decreases the frequency of angina and reduces the need for nitrates. Anti-ischemic effects are not associated with heart rate or systolic blood pressure changes.  

I_f Channel Inhibitor  

Example drug: Ivabradine  

I_f channel inhibitor is used for symptomatic treatment of chronic coronary syndromes in patients with normal sinus rhythm who have contraindications or intolerance to beta-blockers and whose heart rate is >60 bpm. This should be considered as an add-on antianginal agent in patients with LVEF <40% and with symptoms not adequately controlled or as part of initial treatment in properly selected patients. This is an effective antianginal agent. This may be used in combination with beta-blockers in patients whose resting heart rate remains high. This is reported to be non-inferior to Amlodipine or Atenolol in treating ischemia or angina in patients with chronic coronary syndromes.  

I_f channel inhibitor selectively inhibits cardiac pacemaker current I_f which controls spontaneous diastolic depolarization in the sinoatrial node.  

I_f channel inhibitor regulates heart rate without significant negative inotropic effect and other adverse effects associated with beta-blockers. This reduces heart rate and prolongs diastole thereby improving myocardial oxygen balance. This has no effect on blood pressure, myocardial contractility or intracardiac conduction parameters.  

Potassium (K) Channel Activator  

Example drug: Nicorandil  

Potassium channel activator is used for the prevention and long-term treatment of angina. This may be considered as add-on therapy in patients with symptoms not adequately controlled with beta-blockers and/or calcium channel blockers or as part of initial treatment in properly selected patients.  

Potassium channel activator activates adenosine triphosphate-sensitive potassium channels and promotes systemic venous and coronary vasodilation through a nitrate moiety. This increases coronary blood flow and decreases afterload, preload and oxidative injury.  

Potassium channel activator has antianginal and cardioprotective properties.  

This exhibits similar antianginal efficacy and safety as those of beta-blockers, calcium channel blockers and oral nitrates. Tolerance can develop with its long-term use.  

Sodium (Na) Channel Inhibitor  

Example drug: Ranolazine  

Sodium channel inhibitor is indicated for the treatment of chronic angina. This should be considered as add-on therapy in patients with symptoms not adequately controlled with beta-blockers and/or calcium channel blockers or as part of initial treatment in properly selected patients. This can be a substitute for beta-blockers for relief of symptoms in patients with stable ischemic heart disease if beta-blockers are ineffective, contraindicated or cause adverse effects. This can also be used in combination with other agents for stable ischemic heart disease (eg beta-blockers and calcium channel blockers) thus providing additional antianginal benefit. This is a good alternative drug in patients with stable ischemic heart disease who have bradycardia or hypotension because it has no effect on heart rate and blood pressure. 







Sodium channel inhibitor inhibits late inward sodium current which indirectly decreases the sodium-dependent calcium current during ischemic conditions leading to improvement in ventricular diastolic tension and oxygen consumption.  

Sodium channel inhibitor decreases the frequency of angina, improves exercise performance and delays the development of exercise-induced angina and ST-segment depression.   

This should only be used for patients who have not achieved an adequate response with other antianginal drugs because it can prolong the QT interval. 

Lifestyle Modification

It is important to assess the presence of ischemic heart disease risk factors and to treat these effectively. Studies that involved risk modification, which includes weight control, exercise, healthy diet and smoking cessation, have demonstrated benefits in patients with angina and coronary disease. 

Dietary Therapy¹  

The goals of dietary therapy are to reduce the intake of saturated fats to <6% of total calories, trans fatty acids to <1% of total calories and cholesterol to <200 mg/day by avoiding red meat, whole milk products and pastries; limit sodium intake to <2.3 g/day with optimal target of 1.5 g/day; eat fresh fruits (≥200 g/day), vegetables (≥200 g/day), legumes, nuts, soy products, low-fat dairy products and whole grain breads, cereals and pastas; light to moderate alcohol consumption of 1 glass/day or 10 g/day for women and 2 glasses/day or 20 g/day of alcohol for men (1 drink is equivalent to 4 ounces of wine, 12 ounces of beer or 1 ounce of spirits per day); increase intake of polyunsaturated fat which is high in omega-3 fatty acids by eating oily fish, walnuts, sesame seeds, pumpkin seeds or vegetable oils; increase intake of soluble fiber 30-45 g/day which is associated with improvement of cardiovascular disease risk factors (eg lower blood pressure, improved insulin sensitivity, and support of weight loss goals) as well as lower risk of cardiovascular disease events and all-cause mortality in chronic coronary syndromes patients; energy intake should be limited to the amount of energy needed to maintain or obtain a healthy weight (BMI <25 kg/m²); and intake of refined carbohydrates (eg refined cold ready-to-eat breakfast cereal, white bread, white rice) and sugar-sweetened beverages (eg softdrinks, energy drinks, fruit drinks with added sugar) should be limited to reduce the risk of cardiovascular events. 







Start all patients on dietary therapy and adopt a healthy eating habit. A Mediterranean-type diet with intake of higher healthy plant-based foods and lean protein, with lower quantities of fat, helps lower cardiovascular risk factors including insulin resistance, diabetes, dyslipidemia, hypertension and obesity. Dietary Approaches to Stop Hypertension (DASH) diet, which includes intake of vegetables, low-fat/fat-free dairy products, whole grains, legumes and nuts, is associated with a substantial reduction in chronic coronary disease. This is an effective adjunct measure if properly implemented. This has favorable effects on many coronary artery disease risk factors such as hypertension, hypercholesterolemia, obesity and diabetes mellitus. The Prospective Urban Rural Epidemiology (PURE) study recently showed that high carbohydrate intake (>60% of energy) was associated with an adverse effect on total and non-cardiovascular disease mortality whereas a high fat intake (including saturated and unsaturated fatty acids) was associated with a lower risk of total mortality, non-cardiovascular disease mortality and stroke. Limit overall carbohydrate intake especially from refined sources. Recent studies have shown that a diet supplemented by extra-virgin olive oil or nuts reduces the incidence of major cardiovascular events in patients at high risk of cardiovascular events but without prior cardiovascular disease. Antioxidants and other vitamins are not recommended. Vitamins B, C, E, beta-carotene, folate, coenzyme Q10, selenium and chromium are not recommended to prevent cardiovascular risks or improve clinical outcome.  

¹Dietary recommendations may vary between countries. Please refer to available nutritional guidelines from local health authorities. 

Smoking Cessation 

The goals for smoking cessation are to completely stop smoking (including use of electronic cigarette) and avoid exposure to secondhand smoke. 







Smoking cessation is an effective way for the prevention of coronary events. This is the most important reversible risk factor. There are well-conducted epidemiological studies that clearly show cigarette smoking increases the risk for adverse cardiovascular events. The dose-response relationship exists between cigarettes smoked and cardiovascular risks. Smoking status including passive smoking should be assessed systematically. Implement the algorithm for smoking cessation “Ask, Advice, Assess, Assist, Arrange, and Avoid”: Ask the patient about tobacco use at every visit; Advise the smoker to quit; Assess the smoker’s willingness to make a quit attempt; Assist the smoker by providing medications and referral for counseling; Arrange for follow-up; and Avoid exposure to environmental tobacco smoke at home and at work.  

The most effective smoking cessation therapies include both non-pharmacological and pharmacological therapies. The physician’s advice has a significant effect on quit rates. Self-help programs, telephone counseling, behavioral therapy and exercise programs have modest effects. Nicotine-replacement therapy, Bupropion and Varenicline increase the chances of success of a quit attempt. Varenicline may be considered over Bupropion or nicotine-replacement therapy in chronic coronary syndromes patients who regularly smoke. 

Physical Activity

Chronic Coronary Syndromes_Management 9

The goals of physical activity are: Moderate-intensity aerobic exercises of at least 150-300 minutes/week or vigorous-intensity aerobic exercises of at least 75-150 minutes/week are recommended for chronic coronary syndromes patients without contraindications to improve functional capacity and quality of life, and reduce hospitalization and mortality rates; resistance or strength training exercises ≥2 days/week are recommended for chronic coronary syndromes patients without contraindications to improve muscle strength, functional capacity, and cardiovascular risk factor control; light-intensity exercise programs should be started in sedentary patients after adequate exercise-related risk stratification; and increase daily lifestyle activities (eg brisk walking, walking to work, household chores, gardening).   

Exercise improves cardiorespiratory fitness, functional capacity, and quality of life. A reduction of about 10% in mortality and cardiovascular disease is noted when daily step count is increased by 1,000. Exercise training when incorporated into a multifactorial risk factor reduction effort (eg smoking cessation, lipid management, etc) has been shown to improve exercise tolerance in chronic coronary syndrome patients. Exercise training may offer an alternative means of symptom alleviation and improved prognosis in patients with significant coronary artery disease who are candidates for revascularization. Complimentary resistance training for at least 2 days per week is reasonable. Assess the risk with a physical activity history and/or exercise test to guide prognosis and prescription of exercise program. An exercise test is not necessary if the patient undergoes a low- or moderate-intensity level program. Nitroglycerin may be used prior to sexual intercourse to help prevent ischemia. Phosphodiesterase type 5 inhibitors may be given to patients with coronary artery disease with erectile dysfunction but should not be given to patients on nitrates. 

Cardiac Rehabilitation  

Cardiac rehabilitation is indicated for the following chronic coronary syndromes patients: With recent myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft; with stable angina or after heart transplant; and after recent spontaneous coronary artery dissection event. Exercise-based cardiac rehabilitation is an effective way of managing risk factors and achieving a healthy lifestyle in chronic coronary syndrome patients. Home-based cardiac rehabilitation and mobile health interventions should be considered to increase the patient’s long-term adherence to healthy behaviors. This reduces cardiovascular mortality and hospitalizations in patients with coronary artery disease.  

Weight Management 

Chronic Coronary Syndromes_Management 10

The goals for weight management are: BMI for Asian adults should be 18.5-22.9 kg/m² and for American/European adults, this should be 18.5-24.9 kg/m²; waist circumference for Asian: Male <35 in (90 cm), female <31.5 in (80 cm) and American/European: Male <40 in (102 cm), female <35 in (88 cm). The initial weight loss goal is 5-10% from baseline with further reductions if necessary. Measure the body mass index and/or waist circumference every clinic visit. The risks for cardiovascular events are higher in overweight and obese patients. The cardiovascular risk is particularly increased in central obesity and those with extreme obesity. Obesity also contributes to other cardiovascular risk factors such as diabetes mellitus, dyslipidemia and hypertension. Encourage weight maintenance or reduction through an appropriate balance of physical activity, structured exercise, caloric intake and formal behavior programs. Medications or bariatric surgery may be considered in selected patients who cannot achieve adequate weight loss by lifestyle modifications. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, should be considered in chronic coronary syndrome patients without diabetes but with overweight or obesity (BMI >27 kg/m²) to reduce cardiovascular mortality, myocardial infarction or stroke.  

Patient Education

Chronic Coronary Syndromes_Management 11

Effective education about chronic coronary syndromes and ischemic heart disease is important. Educate the patients about the etiology, manifestations, provoking factors, treatment options and prognosis of chronic coronary syndromes and ischemic heart disease to encourage active participation of the patients in their treatment decisions. Patients are more likely to participate in therapeutic and preventive measures if they have a full understanding of the potential benefits. Education about the risks of chronic coronary syndromes typically relieves the patient’s anxieties and concerns. Educate patients about medical adherence to improve knowledge and facilitate behavior change. Reasonable reassurance is essential, and patients may also benefit from relaxation techniques and other ways of stress control. Education should be a part of every patient encounter and should be tailored to the patient’s level of understanding. Individualize the education plan to optimize care and promote wellness. Develop a plan with the patient and hold discussions over time so that the patient is not overwhelmed by changing several behaviors all at one time (eg smoking, diet, exercise, etc). Educate them on self-monitoring skills, recognition of worsening cardiovascular symptoms and appropriate actions to take. Inform them about the common symptoms of stress and depression to lessen stress-related angina symptoms. Discuss treatment goals and strategies to improve compliance. Shared decision-making between patient and physician is important to help maximize patient engagement in medical decision-making, increase patient knowledge about their care, and align treatment decisions with patient preferences. Enlist the family members into the educational process to assist the patient in achieving lifestyle modifications.  

Treatment Regimen  

Treatment regimen should be individualized. Explain the medication management and cardiovascular risk reduction strategies. Emphasize the importance of lifestyle modifications and medication adherence for managing symptoms and retarding disease progression. Adherence to a medication regimen is more likely to be followed by a patient who is adequately counseled about their prescribed medications. Poor compliance can lead to increased morbidity and mortality. Review all therapeutic options including the risk-benefit profile.  

Revascularization

The objectives of revascularization are to improve survival and diminish or eradicate symptoms. This may be considered in combination with optimal medical therapy. Decisions should be based on the patient’s symptoms, the presence of significant obstructive coronary artery stenosis, the amount of related documented ischemia and the expected benefit to prognosis and/or symptoms. Either non-invasive or invasive functional assessment may be used to evaluate angiographic stenoses before revascularization, unless very high grade (>90% diameter stenosis). For consideration of revascularization, patients with high event risk may be considered for invasive testing even though there are mild or no symptoms. Discussion with a Heart Team which includes representatives from interventional cardiology, cardiac surgery, non-interventional cardiology and other specialties is recommended in order to define the optimal treatment strategy. Evaluation of procedural risks and post-procedural outcomes is recommended in patients with complex coronary artery disease where revascularization is being considered. Calculation of SYNergy Between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) score is recommended in patients with multivessel obstructive coronary artery disease to assess the anatomical complexity of disease. Intracoronary pressure measurement using fractional flow reserve or instantaneous wave-free ratio or computation using QFR is recommended to guide lesion selection for intervention in patients with multivessel disease. This should be considered at the end of the procedure to identify patients at high risk of persistent angina and subsequent clinical events. This may also be considered at the end of the procedure to identify lesions that are potentially amenable to treatment with additional percutaneous coronary intervention.  

Choosing between revascularization or medical therapy alone is recommended in chronic coronary syndrome patients with LVEF ≤35% after careful assessment of coronary anatomy, correlation between coronary artery disease and left ventricular dysfunction, comorbidities, life expectancy, individual risk-to-benefit ratio and patient perspectives by the Heart Team. Patient profile, lesion location, coronary anatomy, procedural factors, left ventricular ejection fraction, patient preferences and expected outcomes are recommended factors for the selection of revascularization modality. Clinical (eg age, gender, comorbidities), anatomical (eg single/multivessel disease, SYNTAX score), technical (eg incomplete/complete vascularization, post coronary artery bypass graft/percutaneous coronary intervention) and environmental factors (eg patient preference, local cost) should be discussed before the benefit of revascularization can be anticipated. Antiplatelet therapy should be given to patients with multivessel disease who are not eligible for revascularization. 

Indications for Myocardial Revascularization  

Myocardial revascularization is recommended in chronic coronary syndrome patients with LVEF >35% in addition to guideline-directed medical therapy with: Functionally significant left main stem disease (>50% stenosis) to improve survival; functionally significant single- or 2-vessel disease involving the proximal left anterior descending to reduce long-term cardiovascular mortality and risk of spontaneous myocardial infarction; and functionally significant 3-vessel disease to reduce long-term cardiovascular mortality and risk of spontaneous myocardial infarction. Myocardial revascularization is recommended in chronic coronary syndrome patients with persistent angina or angina equivalent despite guideline-directed medical therapy to improve symptoms. There are a high likelihood of success and an acceptable risk of morbidity and mortality. The quality of life remains unacceptable under conservative management. The patient prefers an interventional rather than a pharmacological therapy and is fully informed of the benefits and risks of the procedure.

Factors to be Considered for the Selection of the Method of Revascularization  

The factors to be considered for the selection of the method of revascularization are the risk of peri-procedural morbidity and mortality; the number of involved coronary vessels; the likelihood of success with consideration of the technical suitability of lesions for angioplasty or surgical bypass; the risk of restenosis or graft occlusion; the completeness of revascularization; the presence of comorbid illnesses; expertise of the cardiac and medical team; hospital facilities in cardiac surgery and interventional cardiology; and the patient’s preference. 

Appropriate Use Criteria (AUC) for Revascularization  

The Appropriate Use Criteria (AUC) is recommended by the ACC Appropriate Use Criteria Task Force, American Association for Thoracic Surgery (AATS), AHA, American Society of Echocardiography (ASE), American Society of Nuclear Cardiology (ASNC), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Cardiovascular Computed Tomography (SCCT), and the Society of Thoracic Surgeons (STS). This is based on indication, symptoms, present therapy and history of revascularization. For patients with one-vessel disease, percutaneous coronary intervention only for patients with one-vessel disease without proximal left anterior descending coronary artery or proximal left dominant left circumflex artery involvement with low- to high-risk findings on non-invasive testing, with no stress test result or stress tests results are indeterminate and fractional flow reserve of ≤0.80 who are currently on ≥2 antianginal medications and for both percutaneous coronary intervention and coronary artery bypass graft, patients with one-vessel disease with proximal left anterior descending coronary artery or proximal left dominant left circumflex artery involvement with intermediate- to high-risk findings on non-invasive testing who are currently on 1 antianginal medication; and in patients with one-vessel disease with proximal left anterior descending coronary artery or proximal left dominant left circumflex artery involvement with low- to high-risk findings on non-invasive testing, with no stress test result or stress test results are indeterminate and fractional flow reserve of ≤0.80 who are currently on ≥2 antianginal medications.  

For patients with two-vessel disease: 

	Findings on Non-invasive Testing		No stress test done or stress test results indeterminate and FFR ≤0.80 in both vessels	Ischemic symptoms present	Current Antianginal Therapy			Recommended Revascularization Method
	Low-risk	Intermediate- to High-risk			None	1	≥2	PCI	CABG
No proximal LAD coronary artery involvement		+	+	+		+		+
	+			+			+	+
		+	+	+			+	+	+
Proximal LAD coronary artery involvement and (-) diabetes	+			+			+	+	+
		+			+			+	+
		+	+	+		+		+	+
		+	+	+			+	+	+
Proximal LAD coronary artery involvement and (+) diabetes		+			+1				+
	+			+		+			+
	+			+			+	+	+
		+	+		+				+
		+	+	+		+		+	+
		+	+	+			+	+	+
1Also applicable for patients with antianginal therapy. Reference: Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017 Mar;69.

For patients with three-vessel disease:

	Findings on Non-invasive Testing		Diabetes		Ischemic symptoms present	Current Antianginal Therapy			Recommended Revascularization Method
	Low-risk	Intermediate- to High-risk	Present	Absent		None	1	≥2	PCI	CABG
Low Disease Complexity	+			+	+			+	+	+
		+		+		+1				+
		+		+		+			+	+
		+		+	+		+	+	+	+
	+		+		+		+			+
	+		+		+			+	+	+
		+	+			+1				+
		+	+			+				+
		+	+		+		+	+	+	+
Intermediate or High Disease Complexity	+			+		+				+
	+			+	+		+	+		+
		+		+		+1				+
		+		+	+		+	+		+
	+	+	+			+1				+
	+	+	+		+		+	+		+
1Also applicable for patients with antianginal therapy. Reference: Patel MR, Calhoon JH, Dehmer GJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 Appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017 Mar;69.

Contraindications to Revascularization

The contraindications to revascularization are patients with 1- or 2-vessel disease without significant proximal left anterior descending artery stenosis who are asymptomatic or have only mild symptoms and have no adequate trial of pharmacological therapy or have no demonstrable ischemia or only a limited area of ischemia/viability on non-invasive testing; borderline coronary stenosis (50-70%) in locations other than the left main coronary artery and no ischemia on non-invasive tests; non-significant coronary stenosis (<50%); and high risk of procedure-related morbidity or mortality (>10-15% mortality risk) unless the risk is balanced by an expected significant improvement in quality of life or survival.

Percutaneous Coronary Intervention (PCI)

Percutaneous coronary intervention is recommended in the following: As an alternative to coronary artery bypass graft in chronic coronary syndromes patients with significant left main coronary stenosis of low complexity (SYNTAX score ≤22); over medical therapy alone in chronic coronary syndromes patients with significant single- or double-vessel disease involving the proximal left anterior descending and with inadequate response to guideline directed medical therapy to improve symptoms and outcomes; symptomatic chronic coronary syndromes patients with single- or double-vessel disease not involving the proximal left anterior descending and with inadequate response to guideline directed medical therapy to improve symptoms; and in chronic coronary syndromes patients with significant 3-vessel disease of low to intermediate anatomic complexity and without diabetes, with preserved left ventricular ejection fraction and inadequate response to guideline directed medical therapy.







Percutaneous coronary intervention should be considered in the following: Chronic coronary syndrome patients with significant left main coronary stenosis of intermediate complexity (SYNTAX score 23-32); chronic coronary syndrome patient with very high surgical risk over pharmacological therapy alone to reduce symptoms and adverse outcomes; and in chronic coronary syndrome patients with multivessel disease and diabetes with very high surgical risk.  

Percutaneous coronary intervention may be considered in the following: As an alternative to coronary artery bypass graft in selected chronic coronary syndrome patients with functionally significant multivessel disease and LVEF ≤35% with high surgical risk or are not operable; chronic coronary syndrome patients with high surgical risk over pharmacological therapy alone; and over medical therapy alone in chronic coronary syndrome patients with left main disease and multivessel disease with high surgical risk.  

Percutaneous coronary intervention is found to have improved symptoms in patients with: ≥1 significant coronary artery stenoses (≥70% diameter) amenable to revascularization and unacceptable angina despite optimal medical therapy; ≥1 significant coronary artery stenoses (≥70% diameter) and unacceptable angina for whom guideline directed medical therapy cannot be implemented because of pharmacological therapy contraindications, adverse effects or patient preferences; previous coronary artery bypass graft, ≥1 significant coronary artery stenoses (≥70% diameter) associated with ischemia and unacceptable; and angina despite guideline directed medical therapy.  

Contraindications for percutaneous coronary intervention include: Significant unprotected left main coronary artery disease (≥50% diameter stenoses) with unfavorable anatomy for percutaneous coronary intervention and patients who are good candidates for coronary artery bypass graft; ≥1 coronary stenoses that are not anatomically or functionally significant (eg <70% diameter non-left main coronary artery stenosis, FFR >0.80, no or mild ischemia on non-invasive testing), involve only the left circumflex or right coronary artery or subtend only a small area of viable myocardium; and unable to meet anatomic (≥50% diameter left main or ≥70% non-left main stenosis diameter) or physiological criteria for revascularization (eg abnormal fractional flow reserve). 

Percutaneous coronary intervention is a less invasive procedure compared to coronary artery bypass graft with lower procedure-related mortality. This is more effective than pharmacological therapy in decreasing symptoms and increasing exercise capacity, with modest improvement in quality of life. However, percutaneous coronary intervention has not been demonstrated to improve survival in patients with stable angina. This may also increase the short-term risk of myocardial infarction and does not lower the long-term risk of myocardial infarction. Intracoronary imaging guidance using intravascular ultrasound or optical coherence tomography (OCT) is recommended for performing percutaneous coronary intervention on anatomically complex lesions particularly at the left main stem, true bifurcations and long lesions.  

Coronary Artery Bypass Graft (CABG) 

Chronic Coronary Syndromes_Management 13

Coronary artery bypass graft is recommended: Over medical therapy alone and as the overall preferred revascularization mode over percutaneous coronary intervention in chronic coronary syndromes patients with low surgical risk and significant left main coronary stenosis to improve survival; over medical therapy alone in chronic coronary syndromes patients with left main disease and multivessel disease with low surgical risk and suitable anatomy; over medical therapy alone in chronic coronary syndromes patients with significant single- or double-vessel disease involving the proximal left anterior descending and with inadequate response to guideline directed medical therapy to improve symptoms and outcomes; over percutaneous coronary intervention in chronic coronary syndromes patients with complex significant single- or double-vessel disease involving the proximal left anterior descending who are less amenable to percutaneous coronary intervention and with inadequate response to guideline directed medical therapy to improve symptoms and reduce revascularization rates; over medical therapy alone in chronic coronary syndromes patients with significant 3-vessel disease of low to intermediate anatomic complexity and without diabetes, with preserved left ventricular ejection fraction and inadequate response to guideline directed medical therapy; over medical therapy alone and percutaneous coronary intervention in chronic coronary syndromes patients with multivessel disease and diabetes with inadequate response to guideline directed medical therapy; and in surgically eligible chronic coronary syndromes patients with functionally significant multivessel disease and LVEF ≤35% in addition to medical therapy. 

Coronary artery bypass graft is preferred over percutaneous coronary intervention in the following patients with chronic coronary syndromes requiring revascularization: With significant left main involvement associated with high-complexity coronary artery disease; and with diabetes and multivessel coronary artery disease with left anterior descending artery involvement. This may be considered in symptomatic chronic coronary syndrome patients with single- or double-vessel disease not involving the proximal left anterior descending and with inadequate response to guideline-directed medical therapy and not amenable to revascularization by percutaneous coronary intervention to improve symptoms.  

Coronary artery bypass graft is found to have improved symptoms in patients with: >1 significant coronary artery stenoses (>70% diameter) amenable to revascularization and unacceptable angina despite guideline directed medical therapy; ≥1 significant coronary artery stenoses (≥70% diameter) and unacceptable angina for whom guideline directed medical therapy cannot be implemented because of pharmacological therapy contraindications, adverse effects or patient preferences; complex 3-vessel coronary artery disease, with or without proximal left anterior descending artery involvement, who are good candidates for coronary artery bypass graft; previous coronary artery bypass graft, >1 significant coronary artery stenoses (>70% diameter) not amenable to percutaneous coronary intervention and unacceptable angina despite guideline directed medical therapy. Contraindications include: ≥1 coronary stenoses that are not anatomically or functionally significant (eg <70% diameter non-left main coronary artery stenosis, FFR >0.80, no or mild ischemia on non-invasive testing), involve only the left circumflex or right coronary artery or subtend only a small area of viable myocardium; and unable to meet anatomic (≥50% diameter left main or ≥70% non-left main stenosis diameter) or physiological criteria for revascularization (eg abnormal fractional flow reserve).   

Coronary artery bypass graft is more effective than pharmacological therapy for relieving anginal symptoms in patients with left main coronary artery disease or 3-vessel coronary artery disease. The presence of left ventricular dysfunction increases the absolute prognostic advantage of surgery over pharmacological therapy. Concurrent administration of guideline-directed medical therapy may substantially improve long-term outcomes in patients treated with coronary artery bypass graft compared to those who are receiving pharmacological therapy alone. Coronary artery bypass graft has been shown to reduce symptoms and ischemia, improve quality of life and provide a better prognosis especially in moderate- to high-risk patients.   

Influenza Vaccination  

Annual influenza vaccination is recommended for patients with ischemic heart disease especially the elderly. This decreases exacerbation of underlying medical condition and risk for mortality in patients with chronic illnesses such as cardiovascular disease.  

Coronavirus Disease 2019 (COVID-19) Vaccine  

Coronavirus disease vaccine is recommended per public health guidelines to reduce COVID-19 complications.  

Pneumococcal Vaccine  

Pneumococcal vaccine may be given to chronic coronary syndrome patients to reduce the cardiovascular morbidity and mortality and all-cause death.