What are the investigations and management options for stable angina?

Investigation and Management of Stable Angina

Initial Diagnostic Approach

Every patient with suspected stable angina requires exercise ECG as the initial non-invasive test of choice to confirm diagnosis and assess prognosis. 1, 2, 3

Essential Baseline Evaluation

• Comprehensive history and physical examination focusing on: 1
  • Character, duration, and triggers of chest pain
  • Cardiovascular risk factors (smoking, diabetes, hypertension, dyslipidemia)
  • Family history of premature coronary disease
• Resting 12-lead ECG in all patients 1
• Fasting lipid panel and glucose to assess metabolic risk factors 1
• Complete blood count and renal function before initiating therapy 1

Exercise Testing Interpretation

• Assess hemodynamic response, workload achieved, symptoms, and ST-segment changes together—not ST changes alone 1, 2
• Exercise ECG has sensitivity 68% and specificity 77% for detecting obstructive coronary disease 1
• Positive test: ≥1mm horizontal or downsloping ST depression at 60-80ms after J-point 1

When Exercise ECG is Inadequate or Uninterpretable

• Use stress echocardiography or myocardial perfusion imaging when: 1
  • Baseline ECG abnormalities (LBBB, LVH with strain, digoxin effect, paced rhythm)
  • Unable to exercise adequately
  • Diagnosis remains uncertain after exercise ECG
  • Need to localize ischemia extent before revascularization
• Stress imaging provides superior sensitivity (85-90%) and specificity (80-85%) compared to exercise ECG alone 1

Special Consideration for Women

• Classical angina symptoms are less reliable in young and middle-aged women compared to men, with higher rates of false-positive exercise tests and greater prevalence of microvascular angina and coronary spasm 1, 2, 4
• Lower threshold for stress imaging in women with typical symptoms but equivocal exercise ECG 1

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Management Strategy: Dual Therapeutic Goals

Management requires two distinct strategies that cannot be achieved with the same medications: prognostic therapy (preventing MI and death) and symptomatic therapy (reducing angina). 2, 4

Immediate Prognostic Therapy (Start in ALL Patients)

These medications reduce mortality and MI risk but do NOT relieve symptoms: 2, 4

1. Aspirin 75-100 mg Daily

• Mandatory for all patients without contraindications 1, 2, 4, 3
• Reduces cardiovascular mortality and morbidity with doses 75-325 mg showing similar efficacy 2

2. High-Intensity Statin Therapy

• Target LDL-C <70 mg/dL when possible 1, 2, 3
• Initiate regardless of baseline cholesterol due to mortality benefits 2
• Use atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily 1

3. ACE Inhibitors

• Indicated for patients with: 1, 2, 4, 3
  • Coexisting ventricular dysfunction (LVEF <40%)
  • Hypertension
  • Diabetes
  • Prior MI with LV dysfunction
  • Other high-risk features (multivessel disease, chronic kidney disease)

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Symptomatic Anti-Anginal Therapy Algorithm

These medications improve quality of life but do NOT reduce mortality or MI risk: 2, 4

Acute Symptom Relief (All Patients)

• Sublingual nitroglycerin 0.3-0.6 mg as needed for acute episodes and situational prophylaxis 1, 2, 4, 3
• Instruct patients to sit during first use to prevent hypotension 4
• If angina does not respond to nitroglycerin, consider acute MI and seek emergency care 3

Step 1: First-Line Anti-Anginal Therapy

Beta-blockers are the preferred initial anti-anginal agent due to mortality benefits in post-MI patients and proven symptom control. 1, 2, 4, 3, 5

Recommended Beta-Blocker Regimens:

• Bisoprolol 10 mg once daily 4, 3
• Metoprolol CR/XL 200 mg once daily 4, 3
• Atenolol 100 mg daily 4, 3

Beta-Blocker Considerations:

• Diabetes is NOT a contraindication—diabetic patients benefit equally or more 3
• Contraindications: severe bradycardia (<50 bpm), second/third-degree AV block, decompensated heart failure, severe asthma/COPD with bronchospasm 1, 6
• Optimize dosing of ONE beta-blocker before adding second agent 3

Step 2: Second-Line Options (When Beta-Blockers Fail or Contraindicated)

Add or substitute with calcium channel blocker if beta-blockers are contraindicated, not tolerated, or symptoms persist despite optimal dosing. 1, 3, 5

Calcium Channel Blocker Selection:

• Dihydropyridines (amlodipine 5-10 mg daily): preferred when adding to beta-blocker 3
• Non-dihydropyridines (diltiazem CD 180-360 mg daily or verapamil SR 120-480 mg daily): alternative to beta-blockers when contraindicated 1, 5
• AVOID combining verapamil or diltiazem with beta-blockers in heart failure due to negative inotropic effects 3
• AVOID immediate-release or short-acting dihydropyridines as they increase adverse cardiac events 3

Long-Acting Nitrates (Third-Line):

• Consider only after beta-blockers and calcium channel blockers 1, 5
• Require nitrate-free interval (10-14 hours) to prevent tolerance 1, 6
• Synergistic with beta-blockers by blocking reflex tachycardia 4
• Examples: isosorbide mononitrate 30-120 mg once daily (morning dosing) or isosorbide dinitrate 20-40 mg twice daily (8am and 2pm dosing) 1

Step 3: Novel Second-Line Agents (Add-On Therapy)

If symptoms persist despite two anti-anginal drugs at optimal doses, consider adding ranolazine. 3, 7

Ranolazine:

• Dose: 500 mg twice daily, titrate to 1000 mg twice daily 7
• Particularly effective for microvascular angina (up to 40% of patients have microvascular dysfunction rather than obstructive disease) 2, 4
• In CARISA trial, ranolazine 750-1000 mg twice daily increased exercise duration by 24-34 seconds and reduced angina frequency by 24-36% when added to standard therapy 7
• Does NOT significantly affect blood pressure or heart rate 7

Alternative Second-Line Agents:

• Ivabradine: for patients with heart failure and LVEF <40%, or when beta-blockers contraindicated 3
  • AVOID combining with non-dihydropyridine calcium channel blockers or strong CYP3A4 inhibitors 3
• Nicorandil: potassium channel opener, but safety data in heart failure uncertain 3
  • AVOID combining with nitrates (lacks additional efficacy) 3

Critical Pitfall to Avoid:

Using three anti-anginal drugs simultaneously may provide LESS symptomatic protection than two drugs—switch combinations before attempting triple therapy. 3, 6

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Aggressive Risk Factor Modification

Risk factor modification directly impacts mortality and must be implemented alongside pharmacological therapy. 1, 2, 4, 3

Mandatory Interventions:

• Smoking cessation (directly reduces mortality; nicotine patches safe in CAD) 2
• Mediterranean diet emphasizing vegetables, fruit, fish, poultry 2
• Aerobic exercise 150-300 minutes/week at moderate intensity or 75-150 minutes at vigorous intensity 2
• Weight reduction if BMI >25 kg/m² 1
• Blood pressure control to <140/90 mmHg (<130/80 mmHg if diabetes or CKD) 1
• Strict glycemic control in diabetes (HbA1c <7%) 1

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Coronary Revascularization

Coronary arteriography should be undertaken when symptoms are not satisfactorily controlled by medical therapy with two anti-anginal drugs at optimal doses. 2, 4, 3

Percutaneous Coronary Intervention (PCI):

• Effective for symptom relief when anatomically suitable lesions present 2, 4, 3
• Does NOT reduce mortality or MI risk compared to optimal medical therapy in stable angina 5, 8
• Higher rates of recurrent angina and repeat procedures compared to CABG 5

Coronary Artery Bypass Grafting (CABG):

CABG reduces mortality in specific high-risk subgroups: 2, 4, 3, 5

• Left main stenosis ≥50%
• Three-vessel disease, especially with impaired LV function
• Two-vessel disease with proximal LAD stenosis

CABG provides superior initial symptom relief compared to medical therapy, but outcomes converge at 5-10 years. 5

80% of CABG patients remain angina-free at 5 years post-surgery. 5

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Follow-Up Monitoring

Routine Follow-Up Every 4-6 Months:

• Assess angina frequency, nitroglycerin use, functional capacity, medication adherence 1
• Physical examination focusing on heart rate, blood pressure, signs of heart failure 1
• Fasting lipid panel and glucose annually 1

Repeat Stress Testing Indicated When:

• Significant change in symptoms (worsening angina frequency/severity) 1
• New symptoms suggesting progression (rest angina, nocturnal angina) 1
• Before revascularization to localize ischemia 1

Common Cause of Treatment Failure:

Poor medication adherence—always assess before escalating therapy. 3