Stable Angina Pectoris – Symptoms, Causes & Treatment

Verified clinical guidelines and emergency management protocols.

Protocol Content

STABLE ANGINA PECTORIS – INDIA

CLINICAL MANAGEMENT GUIDELINE

📋 For Healthcare Professionals Only | Not for Public Use

Scope: Diagnosis | Risk Stratification | Anti-Anginal Therapy | Secondary Prevention | Revascularization

Format: Stepwise, action-oriented

Note: This guideline covers chronic stable angina / chronic coronary syndrome (CCS). Acute coronary syndromes (ACS) are covered separately.

🔰 SYMBOL LEGEND

Symbol	Meaning
✅	Recommended / First-line
⚠️	Caution / Monitor
❌	Contraindicated / Avoid
💊	Drug name
🇮🇳	India-specific
📌	Key point
➡️	Next step
🔬	Evidence-based (major trial)

SECTION 1: DEFINITION AND PATHOPHYSIOLOGY

1.1 WHAT IS STABLE ANGINA?

Definition

Stable angina is chest discomfort caused by myocardial ischemia, typically triggered by physical exertion or emotional stress, and relieved by rest or nitrates. Symptoms are predictable and have been stable for at least 2 months.

Key Characteristics

Feature	Stable Angina
Onset	Predictable; Same triggers
Duration	2-10 minutes
Precipitants	Exertion, stress, cold, heavy meals
Relief	Rest (within 5 min); GTN (within 5 min)
Pattern	Stable for ≥ 2 months
At rest	Typically absent

Pathophysiology

FIXED ATHEROSCLEROTIC PLAQUE

│

▼

CORONARY ARTERY STENOSIS

(Usually ≥ 70% luminal narrowing)

│

▼

INADEQUATE BLOOD FLOW DURING

INCREASED OXYGEN DEMAND

│

▼

MYOCARDIAL ISCHEMIA

│

▼

ANGINA SYMPTOMS

Supply-Demand Mismatch

Increased Demand (Triggers)	Decreased Supply
Exercise	Fixed stenosis
Emotional stress	Vasospasm (superimposed)
Cold exposure	Anemia
Heavy meals	Hypotension
Tachycardia	Hypoxia

1.2 ANGINA VS ACS – CRITICAL DISTINCTION

Feature	Stable Angina	ACS (Unstable Angina/MI)
Pattern	Predictable, unchanged	New, worsening, or rest pain
Duration	< 10 minutes	Often > 20 minutes
Rest pain	Rare	Common
Response to GTN	Relieves in < 5 min	May not relieve
ECG at rest	Usually normal	Often abnormal
Troponin	Negative	Elevated (in MI)
Urgency	Outpatient workup	Emergency admission

⚠️ Any change in angina pattern (new onset, increasing frequency, rest pain, prolonged duration) = Unstable → Treat as ACS

1.3 CHRONIC CORONARY SYNDROME (CCS) – MODERN TERMINOLOGY

ESC Classification

Scenario	Description	Relevance
1	Suspected CAD with stable anginal symptoms	This guideline
2	New-onset HF or LV dysfunction with suspected CAD	Needs echo + ischemia testing
3	Stabilized < 1 year after ACS or revascularization	Higher risk; Close follow-up
4	> 1 year after diagnosis or revascularization	This guideline
5	Angina with suspected vasospastic or microvascular	Special subtypes
6	Asymptomatic with CAD detected on screening	Risk stratify

SECTION 2: CLINICAL ASSESSMENT

2.1 HISTORY – CHARACTERIZING CHEST PAIN

Classic Angina Description

Component	Typical Angina
Site	Retrosternal; Central chest
Character	Pressure, tightness, heaviness, squeezing, constriction
Radiation	Left arm (especially ulnar), jaw, neck, back, epigastrium
Duration	2-10 minutes
Precipitants	Exertion, emotional stress, cold weather, heavy meals, sexual activity
Relief	Rest (1-5 min); GTN (1-5 min)
Associated	Dyspnea, sweating, nausea (less common than in ACS)

Atypical Presentations

Population	Common Atypical Features
Women	Fatigue, dyspnea, nausea, back pain; Less classic chest pain
Elderly	Dyspnea; Fatigue; Confusion; “Angina equivalent”
Diabetics	Silent ischemia; Atypical symptoms; Dyspnea alone

📌 In India, patients often present late and may describe symptoms as “gas” or “acidity” – Actively ask about exertional symptoms

Classification of Chest Pain

Type	Criteria	Probability of CAD
Typical Angina	All 3: (1) Substernal discomfort (2) Provoked by exertion/stress (3) Relieved by rest/GTN within 5 min	High
Atypical Angina	2 of 3 criteria	Intermediate
Non-Anginal Chest Pain	0-1 of 3 criteria	Low

2.2 CANADIAN CARDIOVASCULAR SOCIETY (CCS) GRADING

Grade	Description	Example
I	Angina only with strenuous/prolonged exertion	Running, climbing many flights
II	Slight limitation; Angina with moderate exertion	Walking > 2 blocks; Climbing > 1 flight
III	Marked limitation; Angina with mild exertion	Walking 1-2 blocks; Climbing 1 flight
IV	Angina at rest or minimal activity	Unable to do any activity; Rest angina

📌 CCS Grade guides symptom severity and treatment intensity

2.3 HISTORY – ADDITIONAL QUESTIONS

Cardiovascular Risk Factors

Risk Factor	Ask About
Hypertension	Duration; Control; Medications
Diabetes	Duration; Control; Complications
Dyslipidemia	Known? On statins?
Smoking	Pack-years; Current vs former
Family history	Premature CAD (M < 55, F < 65 in first-degree relative)
Obesity	BMI; Waist circumference
Physical inactivity	Sedentary lifestyle
Diet	High fat, salt, processed foods 🇮🇳

Comorbidities Affecting Management

Condition	Relevance
COPD/Asthma	Affects beta-blocker choice
Peripheral artery disease	Marker of severe atherosclerosis
CKD	Contrast risk; Drug dosing
Heart failure	Drug selection
Prior stroke/TIA	High CV risk
Erectile dysfunction	Marker of vascular disease; Nitrate contraindication if on PDE5i

Drug History

Ask About	Why
Current anti-anginals	Assess adequacy
Nitrate use	Frequency indicates severity
PDE5 inhibitors (Sildenafil, Tadalafil)	❌ Contraindication to nitrates
NSAIDs	May worsen ischemia; Increase CV risk
Cocaine/Stimulants	Cause vasospasm

2.4 PHYSICAL EXAMINATION

Often Normal in Stable Angina

📌 A normal examination does not exclude significant CAD

What to Look For

Finding	Significance
Blood pressure	Hypertension (risk factor); Hypotension (severe disease, HF)
Heart rate	Tachycardia (anemia, HF); Bradycardia (beta-blocker effect)
Carotid bruits	Associated atherosclerosis
Cardiac murmurs	Aortic stenosis (mimics/causes angina); MR (ischemic)
S3, S4	LV dysfunction
Displaced apex	LV enlargement
Lung crackles	Heart failure
Peripheral pulses	PAD (absent/reduced)
Ankle-brachial index	< 0.9 indicates PAD
Xanthomas, xanthelasma	Dyslipidemia
Arcus cornealis (< 50 yrs)	Dyslipidemia
Signs of anemia	Exacerbating factor

Examination During Angina (If Possible)

Finding	Significance
S4 gallop	Diastolic dysfunction
Transient MR murmur	Papillary muscle ischemia
Hypotension	Severe ischemia
Diaphoresis	Sympathetic activation

2.5 PRE-TEST PROBABILITY OF CAD

Importance

Guides which investigations to order
Avoids unnecessary testing in very low-risk
Avoids missing disease in high-risk

ESC 2019 Pre-Test Probability Table (Updated)

	Typical Angina	Atypical Angina	Non-Anginal	Dyspnea Only
Age	M	F	M	F
30-39	3%	5%	4%	3%
40-49	22%	10%	10%	6%
50-59	32%	13%	17%	6%
60-69	44%	16%	26%	11%
70+	52%	27%	34%	19%

Simplified Approach

PTP	Category	Action
< 5%	Very Low	CAD unlikely; Consider other causes; Generally no testing
5-15%	Low	Consider CTCA or functional testing if clinical suspicion
15-85%	Intermediate	Testing indicated (CTCA preferred; or functional test)
> 85%	High	CAD very likely; Can proceed to ICA if revascularization considered

📌 Most patients fall into intermediate PTP → Need non-invasive testing

Clinical Likelihood Modifiers

Increases Likelihood	Decreases Likelihood
Diabetes	Normal ECG
Hypertension	Normal echo
Dyslipidemia	Low calcium score (0)
Smoking	Young age
Family history of CAD	Female sex
Known atherosclerosis (PAD, carotid)	Atypical symptoms
Abnormal resting ECG

SECTION 3: INVESTIGATIONS

3.1 BASELINE INVESTIGATIONS (ALL PATIENTS)

Test	Purpose
12-lead ECG	Baseline; May show prior MI, LVH, ST-T changes
CBC	Anemia (exacerbating factor)
Fasting glucose / HbA1c	Diabetes (risk factor; affects prognosis)
Lipid profile	LDL, HDL, TG (guides statin therapy)
Creatinine / eGFR	Renal function (contrast, drug dosing)
Electrolytes	Baseline
LFTs	Baseline (before statin)
TSH	Thyroid disease (exacerbating factor)
Chest X-ray	Cardiomegaly, pulmonary congestion, other causes
Echocardiography	LV function; Wall motion abnormalities; Valvular disease

3.2 RESTING ECG

Findings

Finding	Significance
Normal	Does not exclude CAD (50% of stable angina have normal ECG)
Q waves	Prior MI
ST depression (> 0.5 mm)	Ischemia; Prior MI
T wave inversion	Ischemia; Prior MI
LVH	Hypertensive heart disease
LBBB	Affects interpretation of ischemia testing
Arrhythmias	AF, ventricular ectopy

📌 Normal resting ECG does NOT rule out significant CAD

3.3 ECHOCARDIOGRAPHY

Indications

Indication

All patients with suspected angina (baseline LV function)

Suspected heart failure

Murmur on examination

Abnormal ECG

Prior MI

Hypertension with suspected LVH

What to Assess

Parameter	Relevance
LVEF	Prognostic; Guides therapy; Revascularization decision
Regional wall motion abnormalities (RWMA)	Suggests prior MI or ischemia
LV dimensions	Remodeling
Diastolic function	HFpEF
Valvular disease	AS (causes angina); MR (ischemic MR)
Aortic root	If CABG considered

3.4 CHOOSING THE RIGHT DIAGNOSTIC TEST

Test Selection Algorithm

SUSPECTED STABLE ANGINA

│

▼

ASSESS PRE-TEST PROBABILITY

│

┌─────────────┼─────────────┐

│ │ │

▼ ▼ ▼

PTP < 5% PTP 5-85% PTP > 85%

│ │ │

▼ ▼ ▼

Consider NON-INVASIVE Consider

other causes TESTING direct ICA

(no routine INDICATED if revasc.

testing) planned

│

▼

┌──────┴──────┐

│ │

▼ ▼

ANATOMICAL FUNCTIONAL

TEST TEST

│ │

▼ ▼

CT-CA Stress test

(Preferred (Exercise ECG,

if available) Stress echo,

Stress MRI,

MPS/PET)

Anatomical vs Functional Testing

Anatomical (CT Coronary Angiography)	Functional (Stress Testing)
Shows stenosis directly	Shows ischemia
High NPV (rules out CAD)	Confirms functional significance
Radiation exposure	Some modalities radiation-free
Requires good heart rate control	Requires ability to exercise (some)
Preferred initial test (ESC 2019)	Preferred if known CAD or prior revasc

3.5 CT CORONARY ANGIOGRAPHY (CTCA)

When to Use

✅ Preferred When	⚠️ Less Suitable When
Intermediate PTP (15-50%)	Very high PTP (direct ICA better)
To rule out CAD	Extensive calcification (blooming artifact)
Younger patients	AF with poor rate control
Lower calcium score expected	Severe obesity
Unclear diagnosis	Prior stents (metal artifact)

Preparation

Step	Action
1	Heart rate control (target < 60 bpm) – Beta-blocker if needed
2	Hold Metformin if eGFR < 30
3	IV contrast – Check allergy history; eGFR
4	Sublingual GTN before scan (coronary vasodilation)

Interpretation

Finding	Action
Normal coronaries	CAD ruled out; Seek other causes
Non-obstructive CAD (< 50%)	Lifestyle + Secondary prevention; No revascularization
Obstructive CAD (50-90%)	Consider functional testing to assess ischemia
Severe stenosis (> 90%) / Left main / Proximal LAD	Consider ICA for revascularization

Calcium Score (If Done)

Score	Interpretation
0	Very low likelihood of significant CAD
1-99	Mild atherosclerosis
100-399	Moderate atherosclerosis
≥ 400	Extensive atherosclerosis; High risk

3.6 FUNCTIONAL / STRESS TESTING

Types of Stress Tests

Test	Stress Method	Imaging	Pros	Cons
Exercise ECG	Treadmill/Bicycle	None	Cheap; Available 🇮🇳; Functional capacity	Low sensitivity (68%); Needs interpretable ECG
Stress Echocardiography	Exercise or Dobutamine	Echo	No radiation; LV function; Valves	Operator-dependent; Acoustic windows
Stress MRI	Adenosine/Regadenoson	MRI	High accuracy; No radiation	Cost; Availability; Claustrophobia
Myocardial Perfusion Scintigraphy (MPS)	Exercise or Pharmacologic	SPECT	Widely available 🇮🇳; Good sensitivity	Radiation; Attenuation artifacts
PET Perfusion	Pharmacologic	PET	Highest accuracy; Quantitative	Cost; Limited availability

When to Use Which Test

Clinical Scenario	Preferred Test
Able to exercise + Interpretable ECG	Exercise ECG (first-line in resource-limited 🇮🇳)
Able to exercise + Uninterpretable ECG	Stress echo or Stress MPS
Unable to exercise	Pharmacologic stress (Dobutamine echo, Adenosine MPS/MRI)
LBBB, Paced rhythm, WPW	Stress imaging (not exercise ECG)
Known CAD – Assessing ischemia	Stress imaging (MPS, stress echo, stress MRI)
Prior revascularization	Stress imaging
Indeterminate CTCA	Functional test to assess significance

Uninterpretable ECG for Stress Testing

Condition

LBBB

Paced ventricular rhythm

WPW pattern

> 1 mm resting ST depression

Digoxin use

LVH with repolarization abnormality

3.7 EXERCISE ECG (TREADMILL TEST)

Protocol

Bruce protocol (most common): 3-minute stages with increasing speed and grade
Continue until target HR (85% of age-predicted max = 220 - age) or symptoms/signs of ischemia

Positive (Abnormal) Test

Finding	Criteria
ST depression	≥ 1 mm horizontal or downsloping, lasting > 80 ms after J point
ST elevation	≥ 1 mm (indicates transmural ischemia or prior MI)
Angina	Typical symptoms during test
Hypotension	Drop in SBP > 10 mmHg with exercise
Arrhythmias	Ventricular tachycardia

Duke Treadmill Score (Prognosis)

DTS = Exercise time (min) – (5 × ST deviation in mm) – (4 × Angina index)

Angina index: 0 = none; 1 = non-limiting; 2 = exercise-limiting

DTS Score	Risk	Annual Mortality
≥ +5	Low	0.25%
-10 to +4	Intermediate	1.25%
< -10	High	5%

3.8 STRESS ECHOCARDIOGRAPHY

Principle

Ischemia causes regional wall motion abnormalities (RWMA)
Compare rest vs stress images

Stressors

Stressor	Protocol
Exercise	Treadmill or bicycle (preferred if patient can exercise)
Dobutamine	5 → 10 → 20 → 30 → 40 μg/kg/min (+ Atropine if needed)

Interpretation

Finding	Interpretation
New RWMA with stress	Inducible ischemia (positive)
Fixed RWMA (rest and stress)	Prior MI / Scar
Improvement with low-dose dobutamine, worsening at peak	Viable myocardium
Normal at rest and stress	Negative

3.9 MYOCARDIAL PERFUSION SCINTIGRAPHY (MPS / SPECT)

Principle

Radiotracer uptake proportional to blood flow
Compare stress vs rest images
Ischemia = Reduced uptake at stress, normal at rest
Infarct = Reduced uptake at both

Radiotracers

Tracer	Notes
Tc-99m Sestamibi	Most common 🇮🇳
Tc-99m Tetrofosmin	Similar
Thallium-201	Older; Redistribution imaging

Pharmacologic Stress Agents

Agent	Mechanism	Use
Adenosine	Coronary vasodilation	Most common
Regadenoson	A2A selective agonist	Fewer side effects
Dipyridamole	Blocks adenosine reuptake	Alternative
Dobutamine	Inotropic (if adenosine contraindicated)	Bronchospasm, heart block

Interpretation

Pattern	Meaning
Reversible defect	Ischemia (stress-induced)
Fixed defect	Scar / Prior MI
Normal	No significant ischemia
TID (Transient ischemic dilation)	Severe/extensive ischemia
Increased lung uptake	LV dysfunction with stress

Reporting – Extent of Ischemia

% LV Ischemic	Risk Category
< 5%	Low risk
5-10%	Intermediate risk
> 10%	High risk – Consider ICA/revascularization

3.10 INVASIVE CORONARY ANGIOGRAPHY (ICA)

Indications

✅ Indication

High PTP (> 85%) with limiting symptoms despite medical therapy

Non-invasive test suggesting high-risk CAD

Unacceptable angina despite optimal medical therapy

High-risk features on non-invasive testing

Resuscitated sudden cardiac death

Diagnosis uncertain after non-invasive testing

Occupational requirement (pilots, drivers)

High-Risk Features on Non-Invasive Testing (Prompting ICA)

Test	High-Risk Finding
Exercise ECG	Duke score < -10; Early positive (< 5 min); Hypotension; ST elevation
Stress imaging	≥ 10% LV ischemia; Multiple territories; Reduced LVEF with stress
CTCA	Left main > 50%; Proximal LAD > 50%; Three-vessel disease > 70%

Angiographic Findings – Severity

Stenosis	Significance
< 50%	Non-obstructive (no hemodynamic limitation)
50-70%	Moderate – Consider FFR if uncertain
> 70%	Significant – Likely causing ischemia
> 90%	Severe / Critical
Left main > 50%	High risk – Revascularization indicated

Fractional Flow Reserve (FFR)

Concept	Use
Pressure wire measures pressure drop across stenosis	Assesses functional significance of intermediate lesions (50-70%)
FFR ≤ 0.80	Hemodynamically significant – Benefit from PCI
FFR > 0.80	Not significant – Medical therapy

🔬 FAME, FAME 2: FFR-guided PCI reduces unnecessary stenting and improves outcomes

SECTION 4: RISK STRATIFICATION

4.1 WHY RISK STRATIFY?

Purpose

Identify patients who benefit from revascularization (mortality reduction)

Guide intensity of medical therapy

Inform patient discussions

Determine follow-up frequency

4.2 HIGH-RISK FEATURES

Clinical High-Risk

Feature

Diabetes

Prior MI

Prior revascularization (PCI/CABG)

Peripheral artery disease

Chronic kidney disease

LVEF < 50%

CCS Class III-IV angina despite therapy

Anatomical High-Risk (Angiography/CTCA)

Finding

Left main stenosis > 50%

Proximal LAD stenosis > 50%

Three-vessel disease with > 50% stenosis

Two-vessel disease including proximal LAD

Extensive coronary calcification

Functional High-Risk (Stress Testing)

Finding

Large area of ischemia (> 10% LV)

Ischemia at low workload

Hypotension with exercise

Duke treadmill score < -10

Multiple territories with ischemia

LVEF decrease with stress

Transient ischemic dilation (TID)

4.3 RISK CATEGORIES AND MANAGEMENT IMPLICATIONS

Risk Category	Features	Management
Low Risk	Single-vessel non-proximal disease; < 5% ischemia; Good LV function	Optimal medical therapy; Annual follow-up
Intermediate Risk	Single/Two-vessel disease; 5-10% ischemia; Moderate symptoms	Optimal medical therapy; Consider ICA if refractory
High Risk	Left main/Three-vessel; > 10% ischemia; Reduced LVEF; Refractory symptoms	ICA + Consider revascularization

SECTION 5: PHARMACOTHERAPY – ANTI-ANGINAL THERAPY

5.1 GOALS OF TREATMENT

Goal	Target
Symptom relief	CCS Class I or asymptomatic
Improve quality of life	Able to do normal activities
Prevent progression	Secondary prevention
Reduce events	Prevent MI, death

5.2 OVERVIEW OF ANTI-ANGINAL DRUGS

Mechanism Summary

Drug Class	Mechanism	Effect
Beta-blockers	↓ HR, ↓ Contractility, ↓ BP	↓ Myocardial oxygen demand
Calcium channel blockers	Vasodilation; Some ↓ HR	↓ Afterload; ↑ Coronary flow; ↓ Demand
Nitrates	Venodilation (↓ preload); Coronary vasodilation	↓ Demand; ↑ Supply
Ivabradine	↓ HR (If channel)	↓ Demand
Nicorandil	K⁺-ATP opener + Nitrate	↑ Coronary flow; Preconditioning
Ranolazine	Late Na⁺ channel blocker	↓ Ischemia; No hemodynamic effect
Trimetazidine	Metabolic modulator	Shifts metabolism to glucose

5.3 STEPWISE ANTI-ANGINAL THERAPY

Step 1: First-Line Therapy

┌─────────────────────────────────────────────────────┐

│ FIRST-LINE MONOTHERAPY │

│ │

│ Beta-blocker OR Calcium Channel Blocker │

│ (Choose based on patient profile) │

│ │

│ + Short-acting Nitrate (GTN) for acute relief │

└─────────────────────────────────────────────────────┘

Step 2: If Symptoms Persist – Add Second Agent

┌─────────────────────────────────────────────────────┐

│ DUAL THERAPY │

│ │

│ Beta-blocker + DHP-CCB (e.g., Amlodipine) │

│ OR │

│ Beta-blocker + Long-acting Nitrate │

│ OR │

│ CCB + Long-acting Nitrate │

└─────────────────────────────────────────────────────┘

Step 3: If Symptoms Still Persist – Add Third Agent

┌─────────────────────────────────────────────────────┐

│ TRIPLE THERAPY │

│ │

│ Beta-blocker + CCB + Long-acting Nitrate │

│ OR │

│ Add: Ivabradine / Nicorandil / Ranolazine / │

│ Trimetazidine │

└─────────────────────────────────────────────────────┘

Step 4: Refractory Angina – Consider Revascularization

┌─────────────────────────────────────────────────────┐

│ Optimal medical therapy failed │

│ ↓ │

│ Refer for ICA + Revascularization (PCI/CABG) │

└─────────────────────────────────────────────────────┘

5.4 BETA-BLOCKERS

Mechanism

↓ Heart rate
↓ Myocardial contractility
↓ Blood pressure
Net effect: ↓ Myocardial oxygen demand

Drug Options

💊 Drug	Starting Dose	Target Dose	Frequency	Notes
Metoprolol Succinate XL	25-50 mg	100-200 mg	OD	Preferred; Long-acting
Bisoprolol	2.5-5 mg	10 mg	OD	Cardioselective; Good if HF
Atenolol	25-50 mg	100 mg	OD	Widely used 🇮🇳; Less lipophilic
Carvedilol	6.25 mg	25 mg	BD	Also alpha-blocker; If HF/HTN
Nebivolol	2.5-5 mg	10 mg	OD	Vasodilating; Fewer SE

Target

Parameter	Target
Resting HR	55-60 bpm
HR with activity	Avoid > 100 bpm

Side Effects

Side Effect	Management
Bradycardia	Reduce dose; Ensure HR > 50
Hypotension	Reduce dose
Fatigue	May improve; Consider switching
Cold extremities	Switch to vasodilating BB (Nebivolol)
Bronchospasm	Use cardioselective (Bisoprolol); Avoid in severe asthma
Erectile dysfunction	Consider Nebivolol; Add PDE5i if no nitrates
Depression	Monitor; Consider switching
Masking hypoglycemia	Caution in insulin-treated diabetics

Contraindications

❌ Absolute	⚠️ Relative
Severe bradycardia (HR < 50)	Mild asthma (use cardioselective)
2nd/3rd degree AV block (without pacemaker)	PAD (usually tolerated)
Sick sinus syndrome	Diabetes (mask hypo symptoms)
Acute decompensated HF	Depression
Severe hypotension
Severe asthma

📌 Beta-blockers are first-line if: Prior MI, LV dysfunction, HF, Tachycardia

5.5 CALCIUM CHANNEL BLOCKERS (CCBs)

Types

Type	Drugs	Main Effect
Dihydropyridine (DHP)	Amlodipine, Nifedipine, Felodipine	Vasodilation (coronary + peripheral)
Non-DHP (Rate-limiting)	Verapamil, Diltiazem	Vasodilation + ↓ HR + ↓ Contractility

Drug Options

💊 Drug	Starting Dose	Target Dose	Frequency	Notes
Amlodipine	2.5-5 mg	10 mg	OD	Most used; Long-acting; Ankle edema
Nifedipine LA	30 mg	60-90 mg	OD	Long-acting preparation only
Felodipine	2.5-5 mg	10 mg	OD	Similar to Amlodipine
Diltiazem CD	120 mg	360 mg	OD	Rate-limiting; Good if cannot use BB
Verapamil SR	120 mg	240-480 mg	OD-BD	Rate-limiting; Constipation

When to Use Which CCB

Clinical Situation	Preferred CCB
With beta-blocker	DHP (Amlodipine) – Complementary
Beta-blocker contraindicated	Non-DHP (Diltiazem, Verapamil) – Rate control
Tachycardia	Non-DHP (rate-lowering)
Hypertension	Either
Heart failure (HFrEF)	Amlodipine (safe); ❌ Avoid Verapamil/Diltiazem
Vasospastic angina	CCB is first-line (DHP or non-DHP)

Side Effects

DHP CCBs	Non-DHP CCBs
Ankle edema	Bradycardia
Flushing	Constipation (Verapamil)
Headache	Heart block
Reflex tachycardia (short-acting)	Negative inotropy
Gingival hyperplasia

Contraindications

Drug	❌ Contraindications
Verapamil/Diltiazem	HFrEF; Severe LV dysfunction; Bradycardia; Heart block; Concurrent beta-blocker (relative – risk of severe bradycardia/block)
DHP CCBs	Severe aortic stenosis; Hypotension

⚠️ Do not combine Verapamil or Diltiazem with beta-blocker unless under specialist supervision (risk of severe bradycardia and heart block)

5.6 NITRATES

Mechanism

Venodilation → ↓ Preload → ↓ Wall tension → ↓ Oxygen demand
Coronary vasodilation → ↑ Oxygen supply
Dilation of collaterals

Types

Type	Use
Short-acting (GTN)	Acute symptom relief; Pre-exertion prophylaxis
Long-acting (ISMN, ISDN)	Maintenance anti-anginal therapy

Drug Options

💊 Drug	Route	Dose	Duration	Use
Glyceryl trinitrate (GTN)	Sublingual tablet	0.3-0.6 mg	20-30 min	Acute relief
GTN Spray	Sublingual	400 μg/spray	20-30 min	Acute relief
GTN Patch	Transdermal	5-15 mg/24 hr	12-14 hr (remove overnight)	Prophylaxis
Isosorbide mononitrate (ISMN)	Oral	20-60 mg	6-8 hr	Maintenance
ISMN SR	Oral	30-120 mg	12-24 hr	Once daily
Isosorbide dinitrate (ISDN)	Oral	10-40 mg TID	4-6 hr	Maintenance

How to Use Short-Acting GTN

Instruction for Patients

Sit or lie down before using (prevents hypotension)

Place tablet under tongue; Let it dissolve

Or spray under tongue

Can repeat after 5 minutes if pain persists (max 3 doses)

If pain not relieved after 3 doses → Call emergency / Go to hospital

Can use prophylactically before known triggers (climbing stairs, sexual activity)

Nitrate Tolerance – CRITICAL CONCEPT

Problem	Continuous nitrate exposure leads to tolerance (reduced efficacy)
Solution	Nitrate-free interval of 10-14 hours daily
How	Asymmetric dosing; Remove patch at night

Dosing to Avoid Tolerance

Drug	How to Dose
ISMN immediate-release	20 mg at 8 AM and 2 PM (skip evening dose)
ISMN SR	Once daily in the morning
GTN Patch	Apply in morning, remove at bedtime (10-14 hr patch-free)

Side Effects

Side Effect	Management
Headache	Common initially; Often improves; Start low dose; Paracetamol
Hypotension	Take sitting/lying; Reduce dose
Flushing	Usually mild
Reflex tachycardia	Combine with beta-blocker
Syncope	Avoid standing immediately after use

Contraindications

❌ Absolute

PDE5 inhibitor use (Sildenafil, Tadalafil, Vardenafil) – Severe hypotension; Wait 24-48 hrs

Severe aortic stenosis

Hypertrophic obstructive cardiomyopathy (HOCM)

Hypotension (SBP < 90)

Raised intracranial pressure

📌 Always ask about Sildenafil/Tadalafil before prescribing nitrates – Life-threatening interaction

5.7 IVABRADINE

Mechanism

Selective If current inhibitor in SA node
Pure heart rate reduction without affecting BP or contractility

Indication

✅ Use When

Sinus rhythm with HR ≥ 70 bpm

Beta-blocker contraindicated or not tolerated

OR HR ≥ 70 bpm despite maximal beta-blocker

Stable angina or HFrEF

Dosing

💊 Drug	Starting Dose	Target Dose	Frequency
Ivabradine	5 mg	7.5 mg	BD

Key Points

🔬 SIGNIFY: In stable CAD without HF, no mortality benefit; Possible harm in symptomatic angina with HR limiting activity
🔬 SHIFT: Benefit in HFrEF with HR ≥ 70
Only works in sinus rhythm – No benefit in AF
Can combine with beta-blocker

Side Effects

Side Effect	Notes
Bradycardia	Dose-dependent
Phosphenes (visual disturbances)	Transient bright flashes; Usually harmless
Headache
AF	Small increased risk

Contraindications

❌ Contraindication

HR < 60 bpm

Sick sinus syndrome

SA block / 3rd degree AV block (unless pacemaker)

Atrial fibrillation/flutter

Acute MI, Unstable angina

Severe hypotension

Severe hepatic impairment

Concurrent strong CYP3A4 inhibitors

5.8 NICORANDIL

Mechanism

K⁺-ATP channel opener (coronary vasodilation, ischemic preconditioning)
Nitrate moiety (venodilation)
Dual mechanism

Indication

✅ Use When

Second/third-line anti-anginal

Add-on to beta-blocker + CCB

Intolerant to other agents

Dosing

💊 Drug	Starting Dose	Target Dose	Frequency
Nicorandil	5-10 mg	10-20 mg	BD

Key Points

🔬 IONA: Reduced CV events vs placebo
Widely used in India and UK 🇮🇳
Does not develop tolerance (unlike pure nitrates)
Can cause ulceration (oral, GI, perianal) – Rare but serious

Side Effects

Side Effect	Notes
Headache	Common (nitrate effect)
Flushing
Dizziness
GI/Oral/Perianal ulceration	Rare; Stop if occurs; May be severe
Hypotension

Contraindications

❌ Contraindication

Cardiogenic shock

Hypotension

LV failure with low filling pressure

Concurrent PDE5 inhibitors

5.9 RANOLAZINE

Mechanism

Inhibits late sodium current (INa-late)
Reduces intracellular calcium overload
Improves diastolic relaxation
No significant hemodynamic effects (HR, BP unchanged)

Indication

✅ Use When

Add-on therapy when other agents inadequate

Cannot tolerate hemodynamically active drugs

Diabetic patients (may improve HbA1c)

Dosing

💊 Drug	Starting Dose	Target Dose	Frequency
Ranolazine ER	375-500 mg	500-1000 mg	BD

Key Points

🔬 CARISA, ERICA, MERLIN-TIMI 36: Reduces angina frequency; Safe
Does not affect HR or BP – Good for patients with low BP/bradycardia
May reduce HbA1c in diabetics
Can prolong QTc – Avoid with other QT-prolonging drugs

Side Effects

Side Effect	Notes
Dizziness
Constipation
Nausea
Headache
QTc prolongation	Monitor; Avoid with other QT drugs

Contraindications

❌ Contraindication

Severe hepatic impairment

Concurrent strong CYP3A4 inhibitors

Pre-existing QT prolongation

5.10 TRIMETAZIDINE

Mechanism

Metabolic modulator
Inhibits fatty acid oxidation
Shifts cardiac metabolism to glucose (more oxygen-efficient)
Anti-ischemic without hemodynamic effects

Indication

✅ Use When

Add-on therapy

Cannot tolerate hemodynamic agents

Diabetic patients

Commonly used in India 🇮🇳

Dosing

💊 Drug	Starting Dose	Target Dose	Frequency
Trimetazidine MR	35 mg	35 mg	BD
Trimetazidine	20 mg	20 mg	TID

Key Points

Does not affect HR or BP
Approved in Europe, Asia; Not in USA
Widely used in India as add-on 🇮🇳
May cause movement disorders (parkinsonism) – Rare

Side Effects

Side Effect	Notes
GI upset
Headache
Parkinsonism / Movement disorders	Rare; Stop if occurs; Usually reversible
Dizziness

Contraindications

❌ Contraindication

Parkinson’s disease

Parkinsonian symptoms

Tremor

Restless leg syndrome

Severe renal impairment (CrCl < 30)

5.11 ANTI-ANGINAL DRUG SELECTION – PRACTICAL GUIDE

Based on Patient Profile

Patient Profile	Preferred First-Line	Add-On Options
No comorbidities	Beta-blocker OR CCB	Other of BB/CCB; Nitrate
Prior MI	Beta-blocker (mortality benefit)	CCB; Nitrate
Heart failure (HFrEF)	Beta-blocker (evidence-based BB); Can add Amlodipine	Ivabradine; Nitrate; ❌ Avoid Verapamil/Diltiazem
LV dysfunction	Beta-blocker	DHP-CCB (Amlodipine)
Hypertension	Beta-blocker OR CCB	Either
Diabetes	Either (BB may mask hypo)	Ranolazine (HbA1c benefit)
COPD/Asthma (mild)	Cardioselective BB (Bisoprolol); or CCB	CCB preferred if severe
Asthma (severe)	CCB (DHP or non-DHP)	❌ Avoid BB
Bradycardia (HR < 60)	DHP-CCB (Amlodipine)	Nitrates; Ranolazine
Tachycardia	Beta-blocker; Non-DHP CCB	Ivabradine
Peripheral artery disease	CCB	Beta-blockers usually tolerated
Hypotension	Beta-blocker (low dose)	Ranolazine; Trimetazidine (no BP effect)
Elderly	Start low; DHP-CCB or BB
Vasospastic angina	CCB (first-line); Nitrates	❌ Avoid BB (may worsen spasm)
Erectile dysfunction / Using PDE5i	Beta-blocker; CCB	❌ Avoid Nitrates

Drug Combinations

✅ Safe/Recommended Combinations	⚠️ Use with Caution
BB + DHP-CCB (Amlodipine)	BB + Non-DHP CCB (Diltiazem/Verapamil) – Risk of bradycardia/block
BB + Long-acting nitrate	Multiple rate-limiting drugs
CCB + Long-acting nitrate
BB + CCB + Nitrate
Any combination + Ivabradine (if sinus rhythm, HR still > 70)
Any + Nicorandil / Ranolazine / Trimetazidine

5.12 ANTI-ANGINAL SUMMARY TABLE

Drug	Dose Range	HR	BP	Main Role
Beta-blocker	Varies by drug	↓↓	↓	First-line; ↓ demand
DHP-CCB (Amlodipine)	2.5-10 mg OD	–	↓↓	First-line; ↑ supply
Non-DHP CCB (Diltiazem)	120-360 mg OD	↓	↓	If BB contraindicated
Nitrates (ISMN)	20-60 mg BD (asymmetric)	–	↓	Second-line; ↑ supply
Ivabradine	5-7.5 mg BD	↓↓	–	If HR > 70 despite BB
Nicorandil	10-20 mg BD	–	↓	Add-on; Dual mechanism
Ranolazine	500-1000 mg BD	–	–	Add-on; No hemodynamic effect
Trimetazidine	35 mg BD	–	–	Add-on; Metabolic

SECTION 6: PHARMACOTHERAPY – SECONDARY PREVENTION

6.1 RATIONALE

All patients with stable angina / chronic coronary syndrome have established atherosclerotic cardiovascular disease and require aggressive secondary prevention to reduce MI, stroke, and death.

6.2 THE “ABCDE” OF SECONDARY PREVENTION

Letter	Intervention
A	Antiplatelet therapy; ACE-I/ARB
B	Beta-blocker; Blood pressure control
C	Cholesterol management (Statins); Cigarette cessation
D	Diet; Diabetes control
E	Exercise

6.3 ANTIPLATELET THERAPY

All Patients with Stable CAD Should Receive Antiplatelet

Agent	Dose	Indication
💊 Aspirin	75-150 mg OD	✅ First-line for all
💊 Clopidogrel	75 mg OD	Alternative if aspirin intolerant

When to Use DAPT (Dual Antiplatelet Therapy)

Scenario	Duration
Post-PCI (Drug-eluting stent)	6-12 months (can be shorter if high bleed risk)
Post-ACS	12 months
Stable CAD without recent ACS/PCI	Single antiplatelet (Aspirin alone)

Long-Term Antithrombotic Therapy in Stable CAD

Risk Profile	Recommendation
Standard stable CAD	Aspirin 75-150 mg OD
Aspirin intolerant	Clopidogrel 75 mg OD
High ischemic risk + Low bleed risk	Consider Aspirin + Rivaroxaban 2.5 mg BD (COMPASS)
Post-PCI > 1 year	Usually step down to single antiplatelet

🔬 COMPASS Trial

Finding	Low-dose Rivaroxaban (2.5 mg BD) + Aspirin reduced CV death, MI, stroke vs Aspirin alone
Who benefits	High-risk stable CAD/PAD; Low bleeding risk
Tradeoff	↑ Major bleeding (but ↓ fatal bleeding)

📌 For most stable angina patients: Aspirin 75-150 mg OD is sufficient

6.4 LIPID-LOWERING THERAPY (STATINS)

All Patients with Established CAD Should Be on a Statin

Agent	Intensity	Dose
💊 Atorvastatin	High-intensity	40-80 mg OD
💊 Rosuvastatin	High-intensity	20-40 mg OD
💊 Atorvastatin	Moderate-intensity	10-20 mg OD
💊 Rosuvastatin	Moderate-intensity	5-10 mg OD
💊 Simvastatin	Moderate-intensity	20-40 mg OD

LDL Targets (ESC 2019/2021)

Risk Category	LDL Target
Very high risk (documented CAD)	< 55 mg/dL (< 1.4 mmol/L) AND ≥ 50% reduction from baseline
Extremely high risk (recurrent events within 2 years)	< 40 mg/dL (< 1.0 mmol/L)

If LDL Not at Target on Max Statin

Step	Add
1	💊 Ezetimibe 10 mg OD
2	💊 PCSK9 inhibitor (Evolocumab, Alirocumab) if still not at target

🔬 Key Statin Trials in CAD

Trial	Finding
4S, LIPID, CARE	Statins reduce mortality in CAD
TNT	Higher-intensity statin better than moderate
IMPROVE-IT	Ezetimibe + Statin > Statin alone
FOURIER, ODYSSEY	PCSK9 inhibitors reduce CV events

Side Effects of Statins

Side Effect	Management
Myalgia	Check CK; Reduce dose; Try alternative statin
Elevated LFTs	Usually mild; Monitor; Stop if > 3× ULN
Myopathy (rare)	Stop statin; Check CK
Rhabdomyolysis (rare)	Stop statin; Emergency management
New-onset diabetes	Continue statin (CV benefit outweighs)

Statin Intolerance

Step	Action
1	Confirm true intolerance (rechallenge)
2	Try different statin
3	Try lower dose or alternate-day dosing
4	Use Ezetimibe ± Bempedoic acid if truly intolerant

6.5 ACE INHIBITORS / ARBs

Indication in Stable CAD

✅ Indicated In

Stable CAD + Hypertension

Stable CAD + Diabetes

Stable CAD + LV dysfunction (LVEF < 40%)

Stable CAD + CKD with proteinuria

High-risk stable CAD (consider for all)

Drug Options

💊 Drug	Dose
Ramipril	2.5-10 mg OD
Perindopril	4-8 mg OD
Enalapril	5-20 mg BD
Lisinopril	5-20 mg OD
Telmisartan (ARB)	40-80 mg OD

Evidence

Trial	Finding
🔬 HOPE	Ramipril reduces CV events in high-risk patients
🔬 EUROPA	Perindopril reduces CV events in stable CAD
🔬 ONTARGET	Telmisartan equivalent to Ramipril

📌 Consider ACE-I for all patients with stable CAD, especially if other indications present

6.6 BLOOD PRESSURE CONTROL

Target

Population	BP Target
Most CAD patients	< 130/80 mmHg
Elderly (> 65 yrs)	< 140/90 (individualize)

Preferred Agents

Agent	Notes
ACE-I / ARB	First-line if indicated
Beta-blocker	Already on for anti-anginal
CCB	Already on for anti-anginal
Thiazide / Thiazide-like	Add if above insufficient

6.7 DIABETES MANAGEMENT

Targets

Parameter	Target
HbA1c	< 7% (individualize)
Fasting glucose	80-130 mg/dL

Preferred Agents in CAD + Diabetes

Agent	Notes
SGLT2 inhibitors (Empagliflozin, Dapagliflozin)	✅ CV benefit; Reduce HF and CV death
GLP-1 receptor agonists (Liraglutide, Semaglutide)	✅ CV benefit; Reduce MACE
Metformin	First-line; Safe

📌 All diabetic patients with CAD should be on SGLT2i or GLP-1 RA with proven CV benefit

6.8 LIFESTYLE MODIFICATIONS

Smoking Cessation

Intervention	Details
Counseling	Every visit
Nicotine replacement	Patch, gum, lozenge
Pharmacotherapy	💊 Varenicline; 💊 Bupropion

📌 Smoking cessation is the single most effective intervention – Reduces mortality by 36%

Diet

Recommendation

Mediterranean diet (olive oil, fish, nuts, vegetables, fruits, whole grains)

Reduce saturated fats, trans fats

Limit salt (< 5 g/day)

Limit processed and fried foods 🇮🇳

Moderate alcohol (≤ 1-2 drinks/day) or abstain

Exercise

Recommendation

≥ 150 minutes/week moderate-intensity aerobic exercise

Or ≥ 75 minutes/week vigorous-intensity

Plus resistance training 2×/week

Cardiac rehabilitation program – Highly recommended post-PCI/CABG or stable angina

Weight Management

Target

BMI 18.5-24.9 kg/m²

Waist < 90 cm (M), < 80 cm (F) 🇮🇳 (Asian criteria)

Weight loss 5-10% if overweight

6.9 SECONDARY PREVENTION SUMMARY TABLE

Intervention	Target / Recommendation
Aspirin	75-150 mg OD (all patients)
Statin	High-intensity (LDL < 55 mg/dL)
ACE-I	Consider for all; Mandatory if HTN, DM, LV dysfunction
Beta-blocker	If prior MI or LV dysfunction; Otherwise for anti-anginal
BP	< 130/80 mmHg
HbA1c	< 7% (if diabetic)
SGLT2i/GLP-1 RA	If diabetic
Smoking	Cessation
Diet	Mediterranean
Exercise	≥ 150 min/week
Weight	BMI < 25; Waist < 90/80 cm

SECTION 7: REVASCULARIZATION

7.1 GOALS OF REVASCULARIZATION

Goal	Mechanism
Symptom relief	Improve blood flow → ↓ Ischemia → ↓ Angina
Improve prognosis	In selected high-risk anatomy

7.2 WHEN TO CONSIDER REVASCULARIZATION

Indications for Revascularization in Stable Angina

✅ Indication

Angina limiting lifestyle despite optimal medical therapy

Large area of ischemia on functional testing (> 10% LV)

High-risk coronary anatomy (left main, proximal LAD, three-vessel disease with reduced LVEF)

Reduced LVEF (< 35%) with significant CAD and viable myocardium

When Medical Therapy Alone is Reasonable

Scenario

Symptoms controlled with medication

Low-risk anatomy (single-vessel non-proximal, < 5% ischemia)

Patient preference after informed discussion

High procedural risk

7.3 THE ISCHEMIA TRIAL – KEY LEARNINGS

🔬 ISCHEMIA Trial (2020)

Question	Does routine invasive strategy improve outcomes in stable CAD with moderate-severe ischemia?
Patients	Stable CAD, moderate-severe ischemia on stress testing, no left main disease
Comparison	Invasive (angio + revasc) vs Conservative (OMT first, angio if fails)
Result	No difference in death or MI at 5 years
BUT	Invasive group had better symptom relief (especially if severe angina at baseline)

Implications

Takeaway

OMT is a valid first-line strategy for most stable angina

Revascularization is for symptom relief in most stable CAD patients

Prognosis benefit limited to high-risk anatomy (left main, severe LV dysfunction + viability)

Shared decision-making with patient is key

7.4 PCI VS CABG – WHEN TO CHOOSE WHICH

General Principles

Favor PCI	Favor CABG
Single-vessel disease	Left main disease
Two-vessel disease (non-LAD)	Three-vessel disease
Anatomy suitable for PCI	Diabetes + multivessel disease
High surgical risk	Low/Intermediate SYNTAX score
Patient preference	Reduced LVEF
Shorter recovery desired	Complex anatomy (high SYNTAX score)

SYNTAX Score

Score	Definition	Recommendation
0-22	Low	PCI or CABG
23-32	Intermediate	CABG preferred; PCI acceptable
≥ 33	High	CABG preferred

Left Main Disease

Scenario	Recommendation
Left main + Low SYNTAX (< 22)	PCI or CABG
Left main + Intermediate/High SYNTAX	CABG preferred
Unprotected left main + Diabetes	CABG preferred

Multivessel Disease + Diabetes

🔬 FREEDOM Trial: CABG superior to PCI in diabetics with multivessel disease
CABG preferred unless high surgical risk

Heart Team Decision

📌 Complex decisions (left main, multivessel, diabetes) should involve Heart Team (Interventional Cardiologist + Cardiac Surgeon)

7.5 PCI IN STABLE ANGINA

Types of Stents

Type	Notes
Drug-eluting stent (DES)	✅ Standard of care; Lower restenosis
Bare-metal stent (BMS)	Rarely used; High bleed risk; Need for surgery
Bioresorbable scaffold	Largely abandoned (higher thrombosis)

Post-PCI Medications

Medication	Duration
Aspirin	Lifelong
Clopidogrel / Ticagrelor / Prasugrel	6 months (stable CAD); Can shorten to 1-3 months if high bleed risk
Statin	Lifelong
ACE-I	If indicated

Post-PCI Follow-Up

Item	Timing
Clinical review	1 month, then 6-12 monthly
ECG	Baseline post-PCI
Routine stress testing	Not recommended unless symptoms recur

7.6 CABG IN STABLE ANGINA

Indications

✅ Strong Indication

Left main stenosis > 50%

Three-vessel disease (especially with LVEF < 40%)

Two-vessel disease with proximal LAD

Diabetes with multivessel disease

Complex anatomy (high SYNTAX score)

Failed PCI

Conduits

Conduit	Notes
LIMA (Left Internal Mammary Artery)	To LAD; Gold standard; 90% patency at 10 years
RIMA	Second arterial graft
Radial artery	Arterial graft; Good long-term patency
Saphenous vein graft (SVG)	Commonly used; ~50% patency at 10 years

Post-CABG Medications

Medication	Notes
Aspirin	Lifelong; Within 6 hours post-op
DAPT	If SVG only (some use Clopidogrel for 1 year)
Statin	Lifelong; Prevents graft disease
ACE-I	If LV dysfunction or HTN
Beta-blocker	Reduces AF; Continue if prior MI

Post-CABG Follow-Up

Item	Timing
Wound check	1-2 weeks
Clinical review	4-6 weeks, then 6-12 monthly
Cardiac rehabilitation	Start 4-6 weeks post-op
Echo	Before discharge or 6 weeks
Routine angiography	Not recommended unless symptoms

7.7 REVASCULARIZATION SUMMARY

Anatomy	PCI	CABG	OMT Alone
Single-vessel (non-LAD)	✅	–	✅ (if symptoms controlled)
Single-vessel (prox LAD)	✅	✅	Consider
Two-vessel (no prox LAD)	✅	✅	✅ (if symptoms controlled)
Two-vessel (with prox LAD)	✅	✅ Preferred	Consider
Three-vessel (low SYNTAX)	✅	✅	–
Three-vessel (high SYNTAX)	–	✅ Preferred	–
Left main (low SYNTAX)	✅	✅	–
Left main (high SYNTAX)	–	✅ Preferred	–
Diabetes + Multivessel	–	✅ Preferred	–
LVEF < 35% + Viable myocardium	Consider	✅ Preferred	–

SECTION 8: SPECIAL SUBTYPES

8.1 VASOSPASTIC ANGINA (PRINZMETAL’S ANGINA)

Definition

Angina caused by coronary artery spasm rather than fixed stenosis

Clinical Features

Feature	Description
Timing	Rest; Often nocturnal (2-6 AM)
Pattern	Cyclical; Clusters
Triggers	Smoking, Cocaine, Cold exposure, Hyperventilation
ECG during attack	ST elevation (transmural ischemia)
Between attacks	Normal ECG
Coronaries	May be normal or have non-obstructive disease

Diagnosis

Test	Finding
ECG during pain	ST elevation (or depression)
Coronary angiography	Normal or minimal disease
Provocative testing	Acetylcholine or Ergonovine provokes spasm (specialized centers)
Response to nitrates	Rapid relief

Treatment

✅ First-Line	❌ Avoid
CCB (high dose) – Amlodipine, Diltiazem, Verapamil	Beta-blockers (may worsen spasm – unopposed alpha)
Long-acting nitrates	Aspirin (high dose) – May worsen spasm
	Smoking, Cocaine

Drug	Dose
Amlodipine	10 mg OD
Diltiazem	180-360 mg OD
ISMN	30-60 mg OD

Prognosis

Generally good if spasm controlled; Avoid triggers

Risk of MI if prolonged spasm

Risk of arrhythmias during spasm

8.2 MICROVASCULAR ANGINA (CARDIAC SYNDROME X)

Definition

Angina with evidence of ischemia but normal coronary arteries on angiography

Clinical Features

Feature	Description
Demographics	More common in women; Often perimenopausal
Symptoms	Typical angina; May be prolonged; Less responsive to GTN
Risk factors	Hypertension, Diabetes, Dyslipidemia
Stress test	Often positive (ST depression)
Coronary angiography	Normal or non-obstructive CAD
Invasive testing	Abnormal coronary flow reserve (CFR); Abnormal microvascular resistance

Diagnosis

Criteria (All Required)

Typical angina symptoms

Objective evidence of ischemia (stress ECG, imaging)

Normal or non-obstructive CAD on angiography

No other cause (e.g., vasospasm ruled out)

Treatment

Approach	Options
Lifestyle	Exercise, Weight loss, Smoking cessation
Anti-anginals	Beta-blockers, CCB, Nitrates (variable response)
Ranolazine	May be particularly effective
ACE-I	May improve endothelial function
Statins	Endothelial benefit
Low-dose aspirin	Secondary prevention
Aminophylline	Blocks adenosine; May help some
Imipramine	Low dose for visceral pain modulation

Prognosis

Generally good for mortality

Quality of life often impaired

Reassurance and symptom management key

8.3 REFRACTORY ANGINA

Definition

Persistent angina despite optimal medical therapy and when revascularization is not feasible (or already maximized)

Causes of Refractory Angina

Reason

Diffuse/distal CAD not amenable to PCI/CABG

Recurrent disease after multiple revascularizations

No viable myocardium to revascularize

High procedural risk

Microvascular disease

Management Options

Category	Options
Optimize medical therapy	Maximize anti-anginals; Add Ranolazine, Trimetazidine, Nicorandil
Cardiac rehabilitation	Exercise training; Improves symptoms
Enhanced external counterpulsation (EECP)	Non-invasive; Sequential leg compression; Improves perfusion
Spinal cord stimulation	Modulates pain perception
Coronary sinus reducer	Device to redistribute flow
Transmyocardial laser revascularization	Rarely used; Limited evidence
Pain management	Multidisciplinary; Low-dose opioids; Psychological support
Palliative care input	Quality of life focus

SECTION 9: FOLLOW-UP AND MONITORING

9.1 FOLLOW-UP SCHEDULE

Phase	Frequency	Purpose
Initial (After diagnosis/titration)	Every 2-4 weeks	Uptitrate anti-anginals
Stable on therapy	Every 6-12 months	Monitor symptoms, adherence, side effects
After revascularization	1 month, then 6-12 monthly	Symptom recurrence; Secondary prevention
Annual	Yearly	Comprehensive review; Risk factors

9.2 WHAT TO ASSESS AT EACH VISIT

Domain	Assessment
Symptoms	CCS class; Frequency of angina; GTN use
Functional capacity	What can patient do? Limitations?
Adherence	Taking all medications?
Side effects	Hypotension, bradycardia, headache, edema
Risk factors	BP, Weight, Smoking status, HbA1c
Lifestyle	Diet, Exercise, Alcohol
Psychosocial	Depression, Anxiety, Work, Quality of life

9.3 LABORATORY MONITORING

Test	Frequency
Lipid profile	Annually (check LDL at target)
HbA1c	Every 3-6 months (if diabetic)
Creatinine / eGFR	Annually
LFTs	If on statin (baseline, then annually or if symptoms)
CBC	Annually (check for anemia)
Potassium	If on ACE-I/ARB/MRA

9.4 WHEN TO REPEAT INVESTIGATIONS

ECG

Indication

Change in symptoms

New arrhythmia suspected

Routine annual not required if stable

Echocardiography

Indication

Change in clinical status

New murmur

Suspected HF

Before/after revascularization

Not required routinely if stable

Stress Testing

Indication

Worsening or recurrent symptoms

Risk stratification if not done

After revascularization only if symptomatic

Not for routine surveillance in asymptomatic patients

Angiography

Indication

Symptoms refractory to optimal therapy

High-risk features on non-invasive testing

After ACS

Not for routine surveillance

9.5 RED FLAGS – WHEN TO ESCALATE

⚠️ Red Flag	Action
Increasing angina frequency	Review therapy; Consider stress test/angiography
Angina at rest	Exclude ACS; Admit if prolonged/ECG changes
Reduced exercise tolerance	Reassess; Echo; Stress test
New dyspnea (HF symptoms)	Echo; BNP; Optimize therapy
Syncope	Rule out arrhythmia; Aortic stenosis
Non-response to GTN	Suspect ACS

SECTION 10: PATIENT EDUCATION

10.1 UNDERSTANDING ANGINA

Key Messages

Message

“Your heart muscle doesn’t get enough blood during exertion”

“The arteries are narrowed but not blocked”

“Treatment can control symptoms and prevent heart attacks”

“Lifestyle changes are as important as medications”

“Know when to seek emergency help”

10.2 USING GTN (GLYCERYL TRINITRATE)

Patient Instructions

Step	Instruction
1	Stop activity and sit or lie down
2	Place tablet under tongue (or spray under tongue)
3	Let tablet dissolve – do not swallow
4	Wait 5 minutes
5	If pain persists, take second dose
6	Wait 5 more minutes
7	If pain still persists, take third dose
8	If pain not relieved after 3 doses (15 minutes) – CALL AMBULANCE

Additional Instructions

Instruction

Can use before known triggers (climbing stairs, sexual activity)

May cause headache (common), dizziness, flushing

Sit or lie down to avoid falls from low BP

Check expiry date – Replace every 8 weeks if using tablets

Store in original container away from light and heat

Do NOT use if you have taken Viagra/Cialis in past 24-48 hours

10.3 WHEN TO SEEK EMERGENCY HELP

⚠️ Call Ambulance / Go to Emergency If:

Chest pain lasting > 15 minutes

Chest pain not relieved by 3 GTN doses

Chest pain at rest that is new

Severe shortness of breath

Feeling like you might faint

Pain more severe than usual

Associated with sweating, nausea, or sense of doom

10.4 LIFESTYLE ADVICE

Stop Smoking

Message

Single most important change

Reduces heart attack risk by 50% within 1 year

Seek help – Medications and support available

Healthy Diet

Advice

Eat more vegetables, fruits, whole grains, fish

Use olive oil or vegetable oils

Reduce fried foods, red meat, full-fat dairy 🇮🇳

Limit salt – Avoid papad, pickle, processed foods 🇮🇳

Limit sugar and refined carbs

Physical Activity

Advice

Regular exercise is safe and beneficial

Aim for 30 minutes most days

Walking is excellent

Warm up and cool down

Carry GTN during exercise

Stop if chest pain occurs

Consider cardiac rehabilitation

Weight Management

Advice

Maintain healthy weight (BMI < 25)

Reduce waist circumference

Even 5-10% weight loss helps

Alcohol

Advice

Limit to ≤ 1-2 drinks/day

Avoid binge drinking

Can interact with medications

10.5 MEDICATION ADHERENCE

Key Messages

Message

Take all medications as prescribed, even if feeling well

Do not stop without consulting doctor

Each medication has a specific purpose

Report side effects – There are alternatives

Use a pill organizer or reminder app

Bring all medications to each appointment

10.6 SEXUAL ACTIVITY

Advice

Point

Usually safe if can climb 2 flights of stairs without angina

Can use GTN prophylactically before activity

If angina occurs, stop and use GTN

If using Sildenafil/Tadalafil – Do NOT use GTN (dangerous drop in BP) – Wait 24-48 hours

If unsure, discuss with doctor

10.7 TRAVEL

Advice

Point

Generally safe to travel

Carry medications in hand luggage

Carry GTN with you always

Travel insurance recommended

If flying, walk around periodically

Carry a list of medications and doctor’s contact

Know how to access medical care at destination

10.8 DRIVING

Advice (May Vary by Country)

Point

Usually can continue driving if symptoms controlled

Do not drive during angina

If angina occurs while driving, pull over safely, use GTN

Inform insurance company of diagnosis

Professional drivers (truck, bus) may have specific restrictions – Check local regulations

SECTION 11: SUMMARY TABLES

11.1 ANTI-ANGINAL DRUGS SUMMARY

Drug	Starting Dose	Target Dose	HR Effect	BP Effect	Key Use
Bisoprolol	2.5-5 mg OD	10 mg OD	↓↓	↓	First-line
Metoprolol XL	25-50 mg OD	200 mg OD	↓↓	↓	First-line
Amlodipine	2.5-5 mg OD	10 mg OD	–	↓↓	First-line; Safe in HF
Diltiazem SR	120 mg OD	360 mg OD	↓	↓	If BB contraindicated
ISMN	20 mg OD	60 mg BD (asymmetric)	–	↓	Second-line
Ivabradine	5 mg BD	7.5 mg BD	↓↓	–	HR ≥ 70 in sinus
Nicorandil	10 mg BD	20 mg BD	–	↓	Add-on
Ranolazine	375 mg BD	1000 mg BD	–	–	Add-on
Trimetazidine	35 mg BD	35 mg BD	–	–	Add-on

11.2 SECONDARY PREVENTION SUMMARY

Intervention	Target
Aspirin	75-150 mg OD
Statin	LDL < 55 mg/dL
ACE-I	If HTN, DM, LV dysfunction
BP	< 130/80 mmHg
HbA1c	< 7%
Smoking	Cessation
Exercise	≥ 150 min/week
Diet	Mediterranean
Weight	BMI < 25

11.3 INVESTIGATION SELECTION

PTP	Test
< 5%	No testing (unlikely CAD)
5-50%	CTCA (preferred)
50-85%	CTCA or Functional test
> 85%	Consider direct ICA

11.4 REVASCULARIZATION INDICATIONS

Indication

Symptoms despite OMT

High-risk anatomy (LM, proximal LAD, 3VD)

Large area of ischemia (> 10% LV)

Reduced LVEF with viable myocardium

11.5 GTN USE – QUICK REFERENCE

Step	Action
1	Sit or lie down
2	Take GTN (sublingual)
3	Wait 5 min; Repeat if needed (max 3 doses)
4	If not relieved after 15 min → CALL AMBULANCE

📚 ABBREVIATIONS

Abbreviation	Full Form
CAD	Coronary Artery Disease
CCS	Canadian Cardiovascular Society / Chronic Coronary Syndrome
ACS	Acute Coronary Syndrome
UA	Unstable Angina
NSTEMI	Non-ST-Elevation Myocardial Infarction
STEMI	ST-Elevation Myocardial Infarction
MI	Myocardial Infarction
PCI	Percutaneous Coronary Intervention
CABG	Coronary Artery Bypass Grafting
OMT	Optimal Medical Therapy
GDMT	Guideline-Directed Medical Therapy
GTN	Glyceryl Trinitrate
ISMN	Isosorbide Mononitrate
ISDN	Isosorbide Dinitrate
BB	Beta-Blocker
CCB	Calcium Channel Blocker
DHP	Dihydropyridine
ACE-I	Angiotensin-Converting Enzyme Inhibitor
ARB	Angiotensin Receptor Blocker
MRA	Mineralocorticoid Receptor Antagonist
SGLT2i	Sodium-Glucose Cotransporter-2 Inhibitor
GLP-1 RA	Glucagon-Like Peptide-1 Receptor Agonist
LVEF	Left Ventricular Ejection Fraction
LV	Left Ventricle / Ventricular
LAD	Left Anterior Descending Artery
LM	Left Main
RCA	Right Coronary Artery
LCx	Left Circumflex Artery
SVG	Saphenous Vein Graft
LIMA	Left Internal Mammary Artery
DES	Drug-Eluting Stent
BMS	Bare-Metal Stent
FFR	Fractional Flow Reserve
CTCA	CT Coronary Angiography
ICA	Invasive Coronary Angiography
MPS	Myocardial Perfusion Scintigraphy
SPECT	Single-Photon Emission Computed Tomography
PET	Positron Emission Tomography
MRI	Magnetic Resonance Imaging
ECG	Electrocardiogram
PTP	Pre-Test Probability
NYHA	New York Heart Association
HFrEF	Heart Failure with Reduced Ejection Fraction
HFpEF	Heart Failure with Preserved Ejection Fraction
LBBB	Left Bundle Branch Block
LVH	Left Ventricular Hypertrophy
RWMA	Regional Wall Motion Abnormality
CFR	Coronary Flow Reserve
EECP	Enhanced External Counterpulsation
LDL	Low-Density Lipoprotein
HDL	High-Density Lipoprotein
TG	Triglycerides
eGFR	Estimated Glomerular Filtration Rate
CKD	Chronic Kidney Disease
PAD	Peripheral Artery Disease
BP	Blood Pressure
SBP	Systolic Blood Pressure
HR	Heart Rate
bpm	Beats Per Minute
OD	Once Daily
BD	Twice Daily
TID	Three Times Daily
PRN	As Needed
NPV	Negative Predictive Value
DAPT	Dual Antiplatelet Therapy
CV	Cardiovascular
QoL	Quality of Life

📖 REFERENCES

Source	Year
ESC Guidelines on Chronic Coronary Syndromes	2019
ACC/AHA Guideline for Management of Chronic Coronary Disease	2023
ISCHEMIA Trial	2020
COURAGE Trial	2007
FAME / FAME 2 Trials	2009 / 2012
COMPASS Trial	2017
Harrison’s Principles of Internal Medicine	21st Edition
Braunwald’s Heart Disease	12th Edition

Document Version: 1.0

Last Updated: December 2024

For: Healthcare Professionals Only

Disclaimer: Clinical judgment must be exercised for individual patients. Local protocols and resource availability should guide management. This guideline covers stable angina; ACS is covered separately. Do not self-medicate.

End of Guideline

🛡️

Medical Advisory

Clinical guidelines are subject to change. Physicians should exercise their regular clinical judgment. This protocol does not replace individual institutional policies. Verified for Q1 2026.

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