What is the recommended treatment approach for a patient with severe coronary artery disease and atherosclerosis, presenting with symptoms such as chest pain and shortness of breath, and comorbidities including hypertension, hyperlipidemia, and diabetes mellitus?

Management of Severe Coronary Artery Disease with Atherosclerosis

All patients with severe coronary artery disease require comprehensive medical therapy including aspirin, high-intensity statin therapy targeting LDL <55 mg/dL, ACE inhibitor (given hypertension and diabetes), beta-blocker, and aggressive risk factor modification, with invasive coronary angiography (ICA) with FFR recommended for risk stratification when symptoms are refractory to medical treatment or in high-risk clinical profiles. 1, 2

Immediate Pharmacological Management

Antiplatelet Therapy

• Aspirin 75-100 mg daily is mandatory as the foundation of treatment for all patients with chronic coronary syndrome unless contraindicated 2
• Add a proton pump inhibitor given the high gastrointestinal bleeding risk with aspirin in patients with multiple comorbidities 1, 2

Lipid-Lowering Therapy

• Initiate high-intensity statin therapy immediately with a target LDL-cholesterol <55 mg/dL (<1.4 mmol/L) for very high-risk patients 1, 2, 3
• Add ezetimibe if maximum tolerated statin dose fails to achieve LDL goals 1, 2
• Add a PCSK9 inhibitor (evolocumab or alirocumab) if LDL goals remain unmet on statin plus ezetimibe 1, 2

ACE Inhibitor/ARB Therapy

• ACE inhibitor is mandatory given the presence of hypertension, diabetes, and severe coronary disease 1, 2
• Use ARB only if ACE inhibitor is not tolerated 1
• Never combine ACE inhibitor with ARB as this increases adverse events without benefit 1, 2

Beta-Blocker Therapy

• Beta-blockers are essential for both symptom relief and mortality reduction, particularly given the symptomatic presentation with chest pain 1, 2
• Beta-blockers are first-line anti-ischemic agents and should be titrated based on heart rate and blood pressure 1

Diabetes Management

• SGLT2 inhibitors or GLP-1 receptor agonists are recommended given the presence of diabetes and established cardiovascular disease 2

Anti-Ischemic Symptom Control

First-Line Agents

• Beta-blockers and/or calcium channel blockers remain first-line for symptom management 1
• Choice should be adapted to heart rate, blood pressure, and left ventricular function 1

Nitrate Therapy

• Sublingual nitroglycerin for acute symptom relief with expected resolution within 1-5 minutes 2
• If long-acting nitrates are used, prescribe a 10-14 hour nitrate-free interval daily to prevent tolerance 1

Blood Pressure Management

• Target office blood pressure to systolic 120-130 mmHg given the coronary disease 1, 2, 3
• In patients >65 years, target systolic 130-140 mmHg 1
• Beta-blockers and/or calcium channel blockers are preferred given their dual benefit for angina and hypertension 1

Risk Stratification and Revascularization Decision

When to Pursue Invasive Assessment

• ICA with FFR/iwFR is recommended for risk stratification in patients with severe CAD when symptoms are refractory to medical treatment or in high-risk clinical profiles 1
• Risk stratification using stress imaging is recommended for patients with new or worsening symptoms 1

Revascularization Indications

• Myocardial revascularization is recommended when angina persists despite optimal antianginal drug therapy 1, 2
• In high-risk patients with mild or no symptoms on medical treatment, ICA with FFR should be considered for prognostic improvement 1

Lifestyle Modifications (Non-Negotiable)

• Comprehensive lifestyle intervention decreases subsequent cardiovascular events and mortality and must be addressed at every clinical encounter 1
• Mandatory tobacco cessation with quantitative assessment at every visit 2
• Mediterranean, DASH, or AHA diet with saturated fat <7% of total calories 3
• Aerobic physical activity 150-300 minutes per week of moderate intensity 3
• Weight management targeting obesity reduction 1

Multidisciplinary Team-Based Approach

• Team-based care is mandatory to improve health outcomes, facilitate risk factor modification, and optimize health service utilization 2
• Multidisciplinary teams provide support for lifestyle changes and address challenging behavioral aspects 1
• Ongoing individualized patient education on symptom management, lifestyle changes, and medication adherence is required 2

Follow-Up Monitoring

• Regular cardiovascular healthcare visits every 3-6 months initially to reassess risk status, lifestyle modifications, adherence to risk factor targets, and development of new comorbidities 1, 2, 3
• Lipid profile assessment 4-12 weeks after initiating statin therapy to evaluate response 3
• Repeat stress imaging or ICA with functional testing is recommended in the presence of worsening symptoms and/or increased risk status 1
• Periodic resting ECG given diabetes for detection of conduction abnormalities, atrial fibrillation, and silent MI 2

Critical Pitfalls to Avoid

• Do not combine ACE inhibitor with ARB as this increases harm 1, 2
• Do not use ticagrelor or prasugrel as part of triple antithrombotic therapy with aspirin and oral anticoagulation 1, 2
• Do not neglect proton pump inhibitor in patients on antiplatelet therapy at high GI bleeding risk 2
• Do not use coronary CTA as a routine follow-up test for patients with established CAD 1
• Do not perform ICA solely for risk stratification without clinical indication 1

Special Considerations for This Patient

Given the constellation of severe CAD with symptomatic presentation (chest pain, shortness of breath) plus multiple comorbidities (hypertension, hyperlipidemia, diabetes), this patient represents a very high-risk profile requiring aggressive medical optimization before considering revascularization 1. The presence of symptoms despite presumed medical therapy suggests either inadequate medical optimization or need for revascularization, making invasive coronary angiography with FFR assessment appropriate for both risk stratification and revascularization planning 1.