What is the recommended immediate and long‑term management, including medications and diagnostic testing, for a patient with known or suspected coronary artery disease?

Management of Coronary Artery Disease

All patients with known or suspected coronary artery disease should immediately receive aspirin 75-100 mg daily, high-intensity statin therapy, short-acting sublingual nitroglycerin, and be enrolled in exercise-based cardiac rehabilitation, as this combination reduces major vascular events and mortality. 1

Immediate Pharmacological Management

Antiplatelet Therapy

• Start aspirin 75-100 mg daily in every patient with established or suspected CAD unless absolute contraindications exist (e.g., active bleeding, severe aspirin allergy). 2, 1
• Clopidogrel 75 mg daily is the only acceptable alternative when aspirin is absolutely contraindicated. 2, 1
• Never use dipyridamole as an antiplatelet agent—it worsens exercise-induced myocardial ischemia in stable angina patients. 2, 1

Lipid-Lowering Therapy

• Initiate high-intensity statin therapy immediately in all CAD patients, targeting LDL-cholesterol <55 mg/dL (1.4 mmol/L) with at least 50% reduction from baseline. 2, 1
• Add ezetimibe if maximum tolerated statin dose fails to achieve LDL targets. 1, 3
• For very high-risk patients not reaching goals on statin plus ezetimibe, add a PCSK9 inhibitor. 1
• Monitor liver function tests early after beginning statin therapy. 2
• Measure creatine kinase in patients taking statins who complain of myopathy symptoms. 2

ACE Inhibitors

• Prescribe an ACE inhibitor (or ARB if ACE-inhibitor intolerant) to all CAD patients, particularly when hypertension, diabetes, heart failure, or left ventricular dysfunction coexist. 2, 1
• The benefit extends beyond blood pressure reduction—ACE inhibitors reduce cardiovascular death, MI, and stroke through vasculoprotective effects. 2
• Never combine ACE inhibitors with ARBs. 1

Beta-Blockers for Symptom Control and Mortality Reduction

• Beta-blockers are first-line therapy for chronic stable angina, controlling heart rate and relieving symptoms while reducing cardiac events and mortality, especially in post-MI patients. 2, 1
• Diabetes mellitus is not a contraindication—diabetic patients benefit equally or more than non-diabetic patients. 2, 1

Short-Acting Nitrates

• Prescribe sublingual nitroglycerin (or nitroglycerin spray) to all CAD patients for immediate relief of effort-induced angina. 1, 3
• Never use nitrates in hypertrophic obstructive cardiomyopathy or with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil). 4, 3

Long-Acting Anti-Anginal Agents

• Long-acting calcium channel blockers are appropriate when beta-blockers are contraindicated or poorly tolerated. 2, 1, 3
• Long-acting calcium channel blockers are generally preferred over long-acting nitrates for maintenance therapy because they provide sustained 24-hour anti-ischemic effects. 2, 1
• Never use immediate-release or short-acting dihydropyridine calcium antagonists—they increase adverse cardiac events. 2, 1

Diagnostic Testing Strategy

Basic First-Line Testing

Before any advanced testing, assess general health, comorbidities, and quality of life—if revascularization is unlikely to be acceptable, reduce testing to a clinically indicated minimum and institute appropriate medical therapy. 2

Basic testing includes: 2

• Full blood count (hemoglobin and white cell count) to identify anemia or infection as causes of ischemia
• Fasting plasma glucose and HbA1c; add oral glucose tolerance test if both are inconclusive
• Creatinine measurement and estimated renal function (creatinine clearance)
• Lipid panel (total cholesterol, LDL, HDL, triglycerides)
• Resting 12-lead ECG
• Resting echocardiography to quantify left ventricular function in all patients
• Thyroid function tests if clinical suspicion of thyroid disorder exists
• High-sensitivity troponin if clinical instability or acute coronary syndrome is suspected

Non-Invasive Imaging for Diagnosis

• Non-invasive functional imaging for myocardial ischemia (stress echocardiography, nuclear perfusion imaging, stress cardiac MRI) or coronary CT angiography is the initial test for diagnosing CAD in symptomatic patients when obstructive CAD cannot be excluded by clinical assessment alone. 2
• Coronary CT angiography is the first-line non-invasive imaging technique in patients with suspected CAD and can guide coronary intervention planning. 5
• Functional imaging for myocardial ischemia is required if coronary CT angiography shows CAD of uncertain functional significance or is non-diagnostic. 2
• Coronary CT angiography is not recommended when extensive coronary calcification, irregular heart rate, significant obesity, or inability to cooperate with breath-hold commands makes good image quality unlikely. 2

Risk Stratification

• Risk stratification using stress imaging, coronary CT angiography, or exercise stress ECG (if significant exercise can be performed and ECG is interpretable) is required in patients with suspected or newly diagnosed CAD. 2
• Left ventricular ejection fraction <50% identifies a higher-risk subgroup. 1
• High-risk anatomical features include left main disease, multivessel disease with reduced LV function, multivessel disease with diabetes, and high-risk non-invasive ischemia testing (>10% of LV mass ischemic). 1

Invasive Coronary Angiography Indications

• Invasive angiography is indicated as an alternative diagnostic test in patients with high clinical likelihood, severe symptoms refractory to medical therapy, or typical angina at a low level of exercise with clinical evaluation indicating high event risk. 2
• Severe angina refractory to maximal medical therapy warrants urgent invasive coronary angiography. 1
• Additional urgent indications include recurrent ischemia (recurrent chest pain or dynamic ST-segment changes), elevated troponin levels, hemodynamic instability, or major arrhythmias (repetitive ventricular tachycardia or ventricular fibrillation). 1
• Invasive coronary angiography should not be performed solely for risk stratification—medical therapy must be optimized first, except in high-risk patients with persistent symptoms. 1, 3
• Invasive functional assessment (FFR or iFR) must be available and used to evaluate stenoses before revascularization, unless very high grade (>90% diameter stenosis). 2

Long-Term Management and Monitoring

Lifestyle Modifications

• Exercise-based cardiac rehabilitation is fundamental and significantly reduces cardiovascular mortality and morbidity while improving risk factor control. 1, 4, 3
• Implement smoking-cessation interventions immediately in all CAD patients. 1
• Cognitive behavioral interventions help individuals achieve and maintain healthy lifestyle changes. 2, 4
• Psychological interventions are recommended to address depression symptoms, which improve quality of life. 2, 1, 4
• Annual influenza vaccination is recommended, especially in elderly patients, to reduce mortality risk. 2, 1, 4, 3

Follow-Up and Monitoring

• Annual control of lipids, glucose metabolism (fasting glucose and HbA1c), and creatinine is required in all patients with known CAD. 2
• Review patient response to medical therapies at 2-4 weeks after drug initiation. 1, 4
• Clinical follow-up at least annually to assess symptoms, functional status, adherence to lifestyle and medical interventions, and monitor for complications. 1
• Patient education about the disease, risk factors, and treatment strategy is essential for long-term adherence and outcomes. 1, 4, 3

Gastrointestinal Protection

• Proton pump inhibitors are recommended for patients on aspirin who have high gastrointestinal bleeding risk. 4

Revascularization Decision-Making

Indications for Revascularization

• In patients with LVEF >35% and functionally significant left main stenosis, coronary revascularization is mandatory to improve survival. 1
• In patients with LVEF >35% and functionally significant three-vessel disease, revascularization is mandatory to improve long-term survival and lower cardiovascular mortality and spontaneous MI. 1
• In patients with LVEF >35% and functionally significant single- or two-vessel disease involving the proximal left anterior descending artery, revascularization is mandatory to reduce long-term cardiovascular mortality and spontaneous MI. 1
• When angina persists despite guideline-directed medical therapy, revascularization of functionally significant obstructive disease is required to relieve symptoms. 1
• For patients with LVEF ≤35%, the decision between revascularization and medical therapy alone should be made by a multidisciplinary Heart Team after evaluating coronary anatomy, the relationship between disease and ventricular dysfunction, comorbidities, life expectancy, risk-benefit balance, and patient preferences. 1

Choice of Revascularization Modality

• For patients at low surgical risk with significant left main coronary stenosis, CABG is preferred over medical therapy alone and is the overall favored revascularization strategy compared with PCI, owing to lower rates of spontaneous MI and repeat revascularization. 1
• When left main disease is of low anatomical complexity (SYNTAX score ≤22) and PCI can achieve completeness of revascularization comparable to CABG, PCI may be offered as an alternative because of its lower invasiveness and non-inferior survival. 1
• In complex multivessel disease, a Heart Team discussion—including interventional cardiology, cardiac surgery, and non-interventional cardiology representatives—is mandatory to select the optimal treatment strategy. 1
• The SYNTAX score should be calculated to assess anatomical complexity of multivessel obstructive disease. 1
• The STS (Society of Thoracic Surgeons) score should be calculated to estimate in-hospital morbidity and 30-day mortality after CABG. 1

Procedural Guidance for PCI

• Intracoronary imaging (intravascular ultrasound or optical coherence tomography) is mandatory when performing PCI on anatomically complex lesions, particularly left main stem, true bifurcations, and long lesions. 1
• Intracoronary pressure measurement (FFR, iFR, or quantitative flow ratio) is mandatory to guide lesion selection for intervention in patients with multivessel disease. 1
• Post-procedural FFR or iFR assessment should be considered to identify patients at high risk of persistent angina and subsequent clinical events. 1

Dual Antiplatelet Therapy After Revascularization

• For patients who undergo bare metal stent placement, the combination of aspirin and clopidogrel is required for at least 4 weeks. 6
• Patients receiving drug-eluting stents require aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months. 6
• Dual antiplatelet therapy (aspirin plus clopidogrel) is required for 6 months after coronary stent implantation. 1
• For patients who have received clopidogrel and are scheduled for coronary bypass surgery, discontinue clopidogrel for 5 days prior to the scheduled surgery. 6

Special Populations and Additional Therapies

Diabetic Patients with CAD

• SGLT2 inhibitors with proven cardiovascular benefit are required for patients with type 2 diabetes and CAD, irrespective of baseline or target HbA1c. 1
• In patients with CAD who are not diabetic but have overweight/obesity (BMI >27 kg/m²), consider the GLP-1 receptor agonist semaglutide to lower cardiovascular mortality, MI, and stroke risk. 1

Anti-Inflammatory Therapy

• Low-dose colchicine 0.5 mg daily may be used in patients with atherosclerotic CAD to reduce MI, stroke, and the need for revascularization. 1

Microvascular and Vasospastic Angina

• For microvascular angina: first-line beta-blocker, second-line add long-acting nitrate. 1
• For vasospastic angina: first-line calcium channel blocker, second-line add long-acting nitrate. 1

Critical Pitfalls to Avoid

• Do not withhold beta-blockers in diabetic patients—they obtain equal or greater therapeutic benefit. 2, 1
• Do not use immediate-release or short-acting dihydropyridine calcium antagonists—they increase adverse cardiac events. 2, 1
• Do not use dipyridamole as an antiplatelet agent—it worsens myocardial ischemia. 2, 1
• Do not combine ACE inhibitors with ARBs. 1
• Do not use nitrates in hypertrophic obstructive cardiomyopathy or with phosphodiesterase inhibitors. 4, 3
• Do not perform coronary angiography solely for risk stratification—optimize medical therapy first. 1, 3
• Do not use coronary CT angiography as a routine follow-up test for patients with established CAD. 1
• Do not avoid combining ivabradine with non-dihydropyridine calcium channel blockers due to potential drug interactions. 3