Stable Angina

Clinical Snapshot

Angina pectoris is chest and/or adjacent-area discomfort caused by myocardial ischemia — an inadequate blood/oxygen supply to the heart muscle relative to demand — most commonly due to obstructive coronary artery disease (CAD), the build-up of atherosclerotic plaque in the coronary arteries.^[1] Stable angina refers to anginal discomfort occurring in a predictable pattern, typically brought on by physical exertion or emotional stress and relieved by rest or nitroglycerin within a few minutes. It is the classic presentation of what current guidelines term chronic coronary syndrome — a broader spectrum that also includes stabilized CAD after a prior acute coronary syndrome (ACS) or revascularization, heart failure/left ventricular dysfunction due to obstructive CAD, microvascular or vasospastic angina, and clinically silent CAD found incidentally or on screening.^[2] This chapter assumes CAD is the underlying cause of angina; other conditions that can produce or worsen myocardial ischemia — tachyarrhythmia, severe or uncontrolled hypertension, severe aortic stenosis, hypertrophic cardiomyopathy, anemia, and functional problems of the coronary tree such as spasm or microvascular dysfunction — must be considered during assessment, both to direct appropriate treatment and to avoid a treatment that could cause harm in an alternative diagnosis (long-acting nitrate therapy, for example, can harm a patient whose angina is actually due to hypertrophic cardiomyopathy).

Recognize the Condition

Typical presentation

Chest discomfort — classically described as squeezing, pressure, heaviness, or tightness rather than sharp pain — that is substernal or in an adjacent area, precipitated by physical exertion or emotional stress, and relieved within about 10 minutes by rest or sublingual nitroglycerin. The pattern is predictable from episode to episode: a similar trigger threshold, a similar character, and reliable relief with rest/nitroglycerin.

Atypical and anginal-equivalent presentation

Women, older adults, and patients with diabetes more often present atypically — dyspnea, fatigue, or epigastric discomfort on exertion without classic chest pain (an "anginal equivalent"). A high index of suspicion in these groups avoids a missed or delayed diagnosis.

Distinguishing stable from unstable presentations

The single most important discrimination on presentation is whether the pattern is still stable — predictable, exertional, reliably relieved by rest/nitroglycerin — or has become unstable: angina now occurring at rest, a new crescendo pattern (more frequent, more severe, more prolonged, or provoked by progressively less exertion than the patient's baseline), or angina no longer relieved by the usual dose of nitroglycerin. Any of these changes should raise suspicion for an acute coronary syndrome rather than a stable-angina exacerbation, and the patient should be managed with an ACS-appropriate urgent-assessment pathway (immediate ECG and troponin) rather than continued outpatient stable-angina management — see the comparison table at the top of Assessment & Diagnosis below.

Risk Factors

Smoking (current or significant past exposure).
Diabetes mellitus.
Dyslipidemia.
Hypertension.
Obesity.
Sedentary lifestyle / lack of regular exercise.
Unhealthy alcohol use.
Chronic psychosocial stress.
Family history of premature CAD (first-degree relative with MI before age 55 if male, before age 65 if female).
Known CAD, prior MI, or prior coronary revascularization (PCI or CABG).
Chronic kidney disease.
Increasing age; male sex carries a higher baseline pretest probability at a given age, though the gap narrows with age (see Assessment & Diagnosis).

Red Flags & Refer

Any of the following suggests the presentation has moved from stable angina to a possible acute coronary syndrome, or to another condition requiring urgent escalation rather than continued outpatient anti-anginal titration — obtain immediate ECG and troponin and manage per the institution's ACS protocol.

Angina occurring at rest, or with minimal exertion clearly below the patient's usual threshold.
A new crescendo pattern — episodes that are more frequent, more severe, longer in duration, or triggered by progressively less activity than the patient's established baseline.
Angina that is not relieved, or only partially relieved, by the patient's usual dose of sublingual nitroglycerin (including after up to 3 doses 5 minutes apart).
Chest discomfort accompanied by diaphoresis, significant dyspnea, syncope or near-syncope, or hemodynamic instability — signs suggesting evolving ACS rather than uncomplicated stable angina.
New or worsening signs of heart failure (orthopnea, peripheral edema, rising dyspnea on exertion) in a patient with known CAD.
Angina in a patient with known or suspected severe aortic stenosis or hypertrophic cardiomyopathy — these need specialist assessment before starting nitrate or other anti-anginal therapy, since standard antianginal treatment can cause harm in these conditions.

Assessment & Diagnosis

Differentiating stable angina from an evolving acute coronary syndrome

Feature	Stable angina	Unstable angina / ACS
Symptom pattern	Predictable, reproducible trigger (exertion, emotional stress)	New onset, crescendo pattern, or occurring at rest
Duration	Typically resolves within about 10 minutes of rest	Often lasts more than 20 minutes, or persists despite rest
Response to nitroglycerin	Reliably relieved within a few minutes	Incomplete or no relief, including after repeated doses
ECG during symptoms	Normal, or unchanged from the patient's known baseline	New ST depression/elevation, T-wave inversion, or new left bundle branch block
Troponin	Normal	May be elevated (NSTEMI) or normal with a still-concerning presentation (unstable angina)
Management urgency	Outpatient work-up; initiate/titrate maintenance anti-anginal therapy	Immediate ECG and troponin, ACS protocol, urgent risk stratification

When the presentation matches the right-hand column, manage the patient using an acute-coronary-syndrome pathway rather than continuing stable-angina management.

History

A thorough history focused on age, sex, and the character of the discomfort (location, quality, precipitating and relieving factors) is the most important tool for estimating the likelihood that obstructive CAD explains the symptoms. Three questions establish the type of chest pain: is it substernal; is it precipitated by exertion; is it relieved within about 10 minutes of rest (or nitroglycerin)? A "yes" to all 3 is typical angina; "yes" to 2 is atypical angina; "yes" to 1 or none is nonanginal chest pain.^[3]

Age (years)	Nonanginal chest pain		Atypical angina		Typical angina
Age (years)	Men	Women	Men	Women	Men	Women
30-39	5%	1%	22%	4%	70%	26%
40-49	14%	3%	46%	13%	87%	55%
50-59	22%	8%	59%	32%	92%	79%
60-69	28%	19%	67%	54%	94%	91%

These figures are the pretest probability that a patient with this symptom pattern, age, and sex has obstructive CAD on angiography — use them to decide how aggressively to pursue further testing, not as a standalone diagnosis.^[3] Also identify modifiable CAD risk factors during the history (see Risk Factors).

Physical examination

Assess for tachycardia and hypertension.
Look for evidence of atherosclerotic disease elsewhere (e.g., arterial bruits).
Assess for valvular heart disease, particularly aortic stenosis.
Assess for decompensated heart failure.

Laboratory testing

CBC (evaluates for anemia as a contributor to or mimic of angina).
Serum creatinine and electrolytes.
Fasting glucose and lipid profile.
Hemoglobin A1c.

Noninvasive cardiovascular testing

Resting 12-lead ECG in every patient.
Echocardiogram when important valvular disease, LV systolic dysfunction, or a cardiomyopathy is suspected.
Physiologic ("stress") testing — exercise or pharmacologic stress (adenosine, dipyridamole, or dobutamine) paired with ECG, echocardiography, or nuclear myocardial perfusion imaging — to support the diagnosis of obstructive CAD and to risk-stratify.
Coronary CT angiography as an alternative anatomic testing strategy; it has a high negative predictive value and offers both diagnostic and prognostic information.

When testing is not indicated: further diagnostic testing for CAD is not needed in a patient with very low pretest probability and a clearly alternative explanation for symptoms, nor in a patient who already has an established indication for coronary angiography (e.g., high-risk clinical presentation) regardless of a noninvasive test result.

Severity classification and risk stratification

Canadian Cardiovascular Society angina functional classification

Class I

Ordinary physical activity (walking, climbing stairs) does not cause angina. Angina occurs only with strenuous, rapid, or prolonged exertion.

Class II

Slight limitation of ordinary activity. Angina occurs walking or climbing stairs rapidly, walking uphill, walking or climbing stairs after meals, in cold or wind, under emotional stress, or only during the first few hours after waking.

Class III

Marked limitation of ordinary physical activity. Angina occurs walking 1-2 level blocks or climbing 1 flight of stairs at a normal pace under normal conditions.

Class IV

Inability to carry on any physical activity without discomfort — anginal symptoms may be present at rest.

Record the CCS class at diagnosis and at follow-up — it is the standard way to communicate angina severity and to track whether therapy is working.^[4]

Duke Treadmill Score

The Duke Treadmill Score is a validated prognostic tool calculated from a standard exercise ECG stress test: Score = exercise time (minutes) − (5 × maximal ST-segment deviation in mm) − (4 × angina index), where the angina index is 0 (no angina during the test), 1 (non-limiting angina), or 2 (angina that forces the test to stop). A score of +5 or higher indicates low risk, −10 to +4 indicates moderate risk, and −11 or lower indicates high risk warranting consideration of angiography.

Unlike the TIMI risk score used in acute coronary syndromes, the Duke Treadmill Score is not a simple point-sum — exercise time and ST deviation are continuous inputs combined with different weighting coefficients into a formula, the same reason the GRACE score does not get a checkbox-style interactive calculator on this platform. Use this table to understand and interpret a treadmill report, but calculate the actual score using the treadmill software or a validated calculator rather than by hand.

Revascularization referral triggers

Refer for coronary angiography with a view to revascularization when angina remains limiting despite optimized medical therapy, or independent of symptom control when coronary anatomy is high-risk — left main stenosis greater than 50%, or three-vessel disease greater than 70% stenosis, particularly with a left ventricular ejection fraction under 50%. Revascularization in stable CAD without one of these high-risk features has not been shown to reduce death or MI compared with optimal medical therapy alone and should not be pursued as a default strategy purely to avoid escalating medical therapy.^[2]

Treatment Targets

Improve quality of life by decreasing or preventing angina and improving exercise tolerance.
Minimize the risk of cardiovascular death and nonfatal MI.
Achieve LDL under 1.8 mmol/L (70 mg/dL), or at least a 50% reduction from baseline on statin therapy.
Achieve guideline blood pressure targets appropriate to the patient's overall risk profile.
Achieve individualized glycemic targets in patients with diabetes.
Achieve smoking cessation.
Treat every modifiable risk factor that promotes the development and progression of CAD.

Choose Initial Treatment

Direct treatment rule

Acute symptom relief

1st line, every patient sublingual nitroglycerin tablet or spray, taken at symptom onset or in advance of an activity known to provoke angina.

Maintenance anti-anginal therapy

1st line a beta-blocker or a nondihydropyridine calcium channel blocker (diltiazem or verapamil) — both are reasonable starting choices given similar efficacy and multiple, overlapping mechanisms; the specific choice depends on patient factors (resting heart rate, LV function, comorbidities) rather than one being universally preferred over the other.

Avoid beta-blockers in suspected or documented coronary vasospasm (vasospastic/Prinzmetal angina) — use a calcium channel blocker and/or nitrate instead in this specific presentation.

2nd line — use when symptoms persist despite an optimized, maximally tolerated dose of first-line therapy add a long-acting nitrate (respecting the mandatory nitrate-free interval — see Non-Pharmacologic Treatment and Drug Tables) or, if first-line therapy was a beta-blocker, add a dihydropyridine calcium channel blocker (amlodipine preferred; avoid combining a nondihydropyridine and a beta-blocker without close heart-rate and AV-conduction monitoring).

3rd line / add-on — use when symptoms persist on optimized combination therapy, or when 1st/2nd-line agents are not tolerated ranolazine.

Special situation ivabradine — restrict to patients who also have heart failure with reduced ejection fraction meeting the drug's Health Canada heart-failure indication (NYHA II-III, sinus rhythm, resting heart rate ≥ 77 bpm, on standard heart failure therapy); it is not independently indicated for angina without a concomitant heart-failure indication in Canada.^[5]

Secondary-prevention pharmacotherapy (shared with acute coronary syndromes)

Antiplatelet, all patients unless contraindicated ASA 80-160 mg once daily indefinitely; use clopidogrel only if ASA is contraindicated or not tolerated.

Lipid-lowering, all patients high-intensity statin regardless of baseline LDL, titrated to an LDL target under 1.8 mmol/L (70 mg/dL) or at least a 50% reduction from baseline; add ezetimibe, then a PCSK9 inhibitor, if the target is not reached on maximally tolerated statin.^[6]

ACE inhibitor (or ARB if not tolerated) for patients with stable CAD who also have hypertension, diabetes, chronic kidney disease, or LV systolic dysfunction; reasonable to consider even without one of these compelling indications given demonstrated benefit in broader high-risk CAD populations.^[7]

Non-Pharmacologic Treatment

Regular aerobic exercise (walking, jogging, cycling, swimming) as tolerated by symptoms.
A heart-healthy diet — vegetables, fruits, nuts, whole grains, and fish, avoiding processed foods high in trans fats.
Smoking cessation — offer pharmacotherapy (nicotine replacement therapy, bupropion, or varenicline) to every patient who smokes; this is one of the highest-yield interventions available.
Alcohol in moderation only.
Stress-management techniques.
Cardiac rehabilitation referral, particularly for higher-risk patients (e.g., those with concomitant heart failure).
Nitrate-free interval: every patient on a long-acting nitrate (oral or transdermal) needs a scheduled 10-12 hour nitrate-free period every 24 hours to prevent pharmacologic tolerance — the antianginal effect of nitrates is lost with continuous around-the-clock exposure. Schedule the nitrate-free interval for a time when symptoms are least likely, usually overnight.^[8]
Sublingual nitroglycerin technique counselling: advise the patient to sit down before taking a dose to reduce the risk of presyncope or syncope, and to expect headache as a common, usually self-limiting side effect. If discomfort persists 5 minutes after 1 dose, a second dose may be taken, and a third after another 5 minutes if needed; if discomfort persists despite 3 doses over about 15 minutes, the patient should seek emergency medical attention immediately rather than continuing to self-treat.
Revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) improves quality of life in patients whose symptoms remain limiting despite optimized medical therapy, and improves longer-term prognosis in patients with high-risk coronary anatomy (see Assessment & Diagnosis for specific referral triggers).
For patients who remain symptomatic despite optimized medical therapy and for whom revascularization is not possible, additional non-pharmacologic options (enhanced external counterpulsation, coronary sinus reduction) may be considered through specialist referral.
Annual influenza vaccination, along with recommended COVID-19 and pneumococcal vaccination.
Review and reinforce medication adherence at every encounter.

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Nitroglycerin, sublingual Preferred	Acute symptom relief, all patients	0.3-0.6 mg SL tablet, or 0.4 mg spray, may repeat every 5 minutes to a maximum of 3 doses	Headache, hypotension, tachycardia, rare syncope	Sit down before dosing. Seek emergency care if discomfort persists after 3 doses over about 15 minutes.
Metoprolol Preferred	1st-line maintenance anti-anginal	Initial 50 mg/day PO, maximum 400 mg/day	Fatigue, bradycardia, hypotension, bronchospasm	Titrate to a resting heart rate of 50-60 bpm. Taper over 10-14 days rather than stopping abruptly.
Bisoprolol Preferred	1st-line maintenance anti-anginal	Initial 2.5 mg/day PO, maximum 20 mg/day	Fatigue, bradycardia, hypotension	Beta1-selective; once-daily dosing. Taper over 10-14 days rather than stopping abruptly.
Diltiazem Preferred	1st-line maintenance anti-anginal, or preferred when beta-blockers are contraindicated (e.g., vasospastic angina)	Initial 120 mg/day PO, maximum 360 mg/day	Headache, dizziness, bradycardia, heart block, constipation	Avoid in significant LV systolic dysfunction. Caution combining with a beta-blocker — additive bradycardia/AV block.
Verapamil Alternative	1st-line maintenance anti-anginal alternative to diltiazem	Initial 80 mg TID PO (or 180 mg/day SR), maximum 480 mg/day	Headache, dizziness, bradycardia, heart block, constipation	Avoid in significant LV systolic dysfunction. Increases digoxin levels by 50-75% within 1 week — monitor levels if combined.
Amlodipine Alternative	2nd-line add-on when 1st-line therapy was a beta-blocker	Initial 2.5 mg/day PO, maximum 10 mg/day	Ankle edema, flushing, headache, hypotension	Preferred dihydropyridine to add onto a beta-blocker rather than a nondihydropyridine CCB.
Isosorbide-5-mononitrate Alternative	2nd-line add-on, long-acting nitrate	Initial 30-60 mg once daily PO, maximum 240 mg/day	Headache, hypotension, dizziness, flushing	Requires a scheduled 10-12h nitrate-free interval daily to prevent tolerance. Start at 30 mg to minimize headache.
Ranolazine Special situation	3rd-line add-on, or when 1st/2nd-line agents are not tolerated	Initial 500 mg PO BID, maximum 1000 mg PO BID (500 mg BID if taking a moderate CYP3A4 inhibitor)	Dizziness, headache, constipation, nausea, QT prolongation	Avoid combining with class IA/III antiarrhythmics. Contraindicated with strong CYP3A4 inhibitors/inducers.
Ivabradine Special situation	Restricted to angina with a concomitant Health-Canada heart-failure indication	Initial 5 mg PO BID, titrated per heart-failure dosing guidance	Bradycardia, visual phosphenes, atrial fibrillation	Not independently approved for angina without heart failure in Canada — see Special Populations.
ASA Preferred	Secondary prevention, all patients	80-160 mg PO once daily indefinitely	GI upset, bleeding, rare bronchospasm	1st-line antiplatelet; continue indefinitely.
Clopidogrel Alternative	Secondary prevention when ASA is contraindicated or not tolerated	75 mg PO once daily	Bleeding, diarrhea, rash	Reserved for ASA intolerance/contraindication in stable CAD without a recent ACS or stent.
Atorvastatin (high-intensity) Preferred	Secondary prevention, all patients regardless of baseline LDL	40-80 mg PO daily	Myalgia, transaminase elevation	Target LDL under 1.8 mmol/L or at least a 50% reduction from baseline.
Ramipril Preferred	Secondary prevention, especially with hypertension, diabetes, CKD, or LV dysfunction	Initial 1.25-2.5 mg PO BID, target 5 mg BID or 10 mg once daily	Cough, hyperkalemia, hypotension, rare angioedema	Switch to an ARB (e.g., candesartan) if cough limits tolerability.

Special Populations

Pregnancy

Stable angina from established CAD is uncommon in patients of reproductive age but occurs, particularly with traditional risk factors present; spontaneous coronary artery dissection is an important alternative diagnosis to consider in this age group and needs its own specialist-directed evaluation. Manage with combined obstetric/cardiology input. Sublingual nitroglycerin, beta-blockers, and nondihydropyridine calcium channel blockers can be used with standard obstetric monitoring. ACE inhibitors, ARBs, and statins are contraindicated in pregnancy — hold these regardless of the non-pregnancy indication and discuss alternative strategies with obstetric cardiology. ASA at low dose (81 mg/day) is compatible with pregnancy.

Breastfeeding

Beta-blockers, nondihydropyridine and dihydropyridine calcium channel blockers, and low-dose ASA are generally considered compatible with breastfeeding. Statin data in lactation are limited; individualize the decision to continue or hold a statin with the patient and her care team given the strength of the underlying secondary-prevention indication.

Older adults

Beta-blockers and heart-rate-lowering calcium channel blockers are, in practice, usually titrated to a resting heart rate target of 50-60 bpm; use a lower starting dose in older or frailer patients, who are more sensitive to bradycardia and hypotension. Advise sitting when taking sublingual nitroglycerin given a higher presyncope/syncope risk with age. If a beta-blocker is desired in a patient with resting bradycardia, an agent with intrinsic sympathomimetic activity (acebutolol, pindolol) may be considered — see Drug Tables.

Renal impairment

Atenolol and nadolol are renally cleared and need dose reduction in significant renal impairment. ACE inhibitor/ARB initiation requires baseline and follow-up creatinine and potassium monitoring, with dose reduction or discontinuation if creatinine rises substantially or hyperkalemia develops. Ranolazine requires caution and closer monitoring in moderate renal impairment.

Hepatic impairment

Most beta-blockers and calcium channel blockers undergo hepatic metabolism — use a lower starting dose and titrate more cautiously in significant hepatic impairment. Ranolazine is contraindicated in clinically significant hepatic impairment.

Hypertrophic cardiomyopathy or severe aortic stenosis

Confirm angina is due to obstructive CAD before starting long-acting nitrate therapy — nitrates can worsen outflow tract obstruction in hypertrophic cardiomyopathy and can cause harmful hypotension in severe aortic stenosis. Refer for specialist assessment if either is suspected rather than proceeding with standard anti-anginal therapy.

Monitoring & Follow-Up

Reassess anginal frequency, CCS functional class, and exercise tolerance at every follow-up visit — this is the primary marker of whether therapy is working. Titrate heart-rate-lowering agents (beta-blockers, diltiazem, verapamil) to a resting heart rate of 50-60 bpm, and titrate dihydropyridine calcium channel blockers and nitrates to maximum symptom relief with minimal adverse effects. Recheck a fasting lipid panel 6-8 weeks after starting or adjusting a statin to confirm the LDL target is met, then periodically thereafter. Recheck creatinine and potassium 1-2 weeks after starting or increasing an ACE inhibitor/ARB dose. Confirm the nitrate-free interval is actually being followed at every visit for a patient on a long-acting nitrate — this is a common, easily corrected source of apparent treatment failure. Reinforce smoking cessation, cardiac rehabilitation attendance, and medication adherence at every encounter. Any change in symptom pattern toward the "unstable" column of the comparison table above warrants immediate reassessment rather than waiting for the next scheduled visit.

Treatment Failure / Next Step

Confirm adherence to the prescribed regimen and confirm correct sublingual nitroglycerin technique (sitting position, timing relative to activity).
Confirm the nitrate-free interval is actually being observed if the patient is on a long-acting nitrate — tolerance from a missed nitrate-free period is a common, easily corrected cause of apparent treatment failure.
Optimize the first-line agent to its maximally tolerated dose before adding a second drug.
Add second-line therapy (a long-acting nitrate with a proper nitrate-free interval, or a dihydropyridine calcium channel blocker if first-line therapy was a beta-blocker) if symptoms persist on optimized first-line monotherapy.
Add ranolazine if symptoms persist on optimized combination therapy, or if first-line agents are not tolerated.
Reassess for reversible contributors to refractory symptoms — anemia, thyrotoxicosis, uncontrolled hypertension, tachyarrhythmia, or uncontrolled comorbid conditions.
Refer for coronary angiography and revascularization work-up if angina remains limiting despite optimized medical therapy, or sooner if high-risk anatomy is already suspected.
Reconsider whether the pattern has actually shifted from stable to unstable — new-onset rest angina, crescendo pattern, or nitroglycerin-unresponsive symptoms require an ACS pathway, not further stable-angina dose escalation.

Common Errors to Avoid

Prescribing a long-acting nitrate without a scheduled nitrate-free interval — tolerance develops and the drug stops working.^[8]
Starting a beta-blocker in suspected or documented vasospastic (Prinzmetal) angina — use a calcium channel blocker and/or nitrate instead.
Stopping a beta-blocker abruptly after chronic high-dose therapy — this can precipitate rebound tachycardia and worsening ischemia; taper over 10-14 days.
Missing the interaction between nitrates and PDE5 inhibitors (sildenafil, tadalafil, vardenafil) — the combination can cause severe, potentially fatal hypotension.
Starting or continuing a nondihydropyridine calcium channel blocker (diltiazem, verapamil) in a patient with significant LV systolic dysfunction.
Combining a nondihydropyridine calcium channel blocker with a beta-blocker without close monitoring for additive bradycardia and AV block.
Using ivabradine for angina alone without a qualifying concomitant heart-failure indication — it is not independently approved for this in Canada, and trial data in angina patients without heart failure did not show a mortality/MI benefit.^[5]
Withholding a statin because baseline LDL "looks fine" — every patient with stable CAD needs a high-intensity statin targeting LDL under 1.8 mmol/L or at least a 50% reduction, regardless of baseline value.
Missing hypertrophic cardiomyopathy or severe aortic stenosis as an alternative cause of angina before starting nitrate therapy, which can worsen either condition.
Treating a change toward an unstable symptom pattern (rest angina, crescendo pattern, nitroglycerin-unresponsive symptoms) as a routine stable-angina follow-up issue instead of an urgent ACS-pathway assessment.
Using NSAIDs (especially COX-2 inhibitors) liberally in a patient with established CAD — if genuinely needed for quality of life, use the lowest effective dose for the shortest possible duration given increased vascular event risk.

Clinical Decision Algorithm

Diagnostic assessment and initial triage

Chest discomfort with an exertional or emotional-stress trigger, relieved by rest/nitroglycerin

Characterize the pattern: is it still predictable and reproducible, or has it changed?

Rest angina, crescendo pattern, or nitroglycerin-unresponsive

Manage as suspected ACS — immediate ECG and troponin, do not continue stable-angina work-up

Pattern remains stable and predictable

History (pretest probability), physical exam, resting ECG, labs (CBC, creatinine, lipids, HbA1c)

Noninvasive testing: stress ECG/echo/nuclear imaging, or coronary CT angiography, guided by pretest probability

High-risk anatomy or refractory symptoms

Refer for coronary angiography and revascularization work-up

CAD confirmed, not high-risk

Assign CCS functional class, proceed to stepwise anti-anginal therapy

Stepwise anti-anginal and secondary-prevention therapy

Stable angina confirmed

Start sublingual nitroglycerin PRN for every patient, plus 1st-line maintenance therapy: beta-blocker or diltiazem/verapamil (avoid beta-blocker if vasospastic angina suspected)

Start secondary prevention: ASA, high-intensity statin (LDL target <1.8 mmol/L or ≥50% reduction), ACE inhibitor/ARB if compelling indication present

Symptoms controlled on optimized 1st-line dose

Continue therapy; reassess CCS class, adherence, and nitrate-free interval at each visit

Symptoms persist on optimized 1st-line dose

Add 2nd-line: long-acting nitrate (with nitrate-free interval) or, if on a beta-blocker, add amlodipine

Symptoms persist

Add ranolazine; reassess for revascularization referral if still limiting

Symptoms controlled

Continue combination therapy; reassess regularly

Drug Tables

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any linked drug name to open its complete Pharmasist Drug Database page.

Nitrates

Effective for both preventing anginal episodes and treating acute attacks. Long-acting formulations require a scheduled 10-12 hour nitrate-free period every 24 hours to prevent pharmacologic tolerance.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Nitroglycerin, sublingual	SL tablet: 0.3-0.6 mg SL, may repeat every 5 minutes SL spray: 0.4 mg SL, may repeat every 5 minutes	Headache (usually resolves with continued use), tachycardia, hypotension, rare syncope, dizziness, flushing	Potentiates hypotensive effect of other vasodilators; potentially fatal hypotension with sildenafil, tadalafil, vardenafil	If discomfort persists 5 minutes after 1 dose, seek medical attention while continuing to a total of 3 doses.
Nitroglycerin, transdermal	Patch: Initial 0.2 mg/h applied and removed daily, maximum 0.8 mg/h	Headache, tachycardia, hypotension, rare syncope, dizziness, flushing, contact dermatitis	Potentiates hypotensive effect of other vasodilators; potentially fatal hypotension with sildenafil, tadalafil, vardenafil	Ensure a 10-12h nitrate-free period daily (typically remove overnight) to prevent tolerance.
Isosorbide dinitrate	SL: 5 mg PRN, may repeat every 5 minutes Oral, immediate-release: 10-30 mg TID PO	Headache, tachycardia, hypotension, rare syncope, dizziness, flushing	Potentiates hypotensive effect of other vasodilators; potentially fatal hypotension with sildenafil, tadalafil, vardenafil	Allow a 10-12h nitrate-free period daily with the oral regimen.
Isosorbide-5-mononitrate	Oral: Initial 30 or 60 mg once daily, maximum 240 mg/day	Headache, tachycardia, hypotension, rare syncope, dizziness, flushing	Potentiates hypotensive effect of other vasodilators; potentially fatal hypotension with sildenafil, tadalafil, vardenafil	Start at the lower dose to minimize headache. Once-daily dosing inherently provides a nitrate-free interval.

Antianginal — Late sodium current inhibitor

Add-on therapy for anginal symptoms, or an option when beta-blockers, calcium channel blockers, and nitrates are not tolerated.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Ranolazine	Initial: 500 mg PO BID Maximum: 1000 mg PO BID (500 mg PO BID if taking a moderate CYP3A4 inhibitor)	Dizziness, headache, constipation, nausea, QT prolongation	CYP3A4 inhibitors (e.g., diltiazem) and P-glycoprotein inhibitors (e.g., cyclosporine) increase ranolazine levels; ranolazine may increase digoxin levels; avoid combining with class IA or III antiarrhythmics	Contraindicated with strong CYP3A4 inhibitors or inducers.

Evidence: ^[9]

Antianginal — Sinus node (If) inhibitor

Reduces heart rate via a mechanism distinct from beta-blockers or calcium channel blockers. In Canada, this drug's Health Canada indication is for heart failure with reduced ejection fraction — use for angina is restricted to patients who also meet that heart-failure indication, not for angina alone.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Ivabradine	Initial: 5 mg PO BID, titrated per heart-failure dosing guidance	Bradycardia, visual phosphenes (luminous phenomena), atrial fibrillation	Strong CYP3A4 inhibitors/inducers significantly alter levels; avoid combining with other significant heart-rate-lowering drugs without close monitoring	Restrict use to patients meeting the Health Canada heart-failure indication (NYHA II-III, sinus rhythm, resting HR ≥77 bpm, on standard heart failure therapy).

Beta-blockers, non-selective

Not first-line if vasospastic angina is suspected. Taper over 10-14 days rather than stopping abruptly — abrupt withdrawal can precipitate rebound tachycardia and worsening ischemia. Contraindicated in asthma and in 2nd-/3rd-degree heart block without a pacemaker.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Nadolol	Initial: 20 mg once daily PO Maximum: 320 mg/day	Fatigue, hypotension, bradycardia, sleep disturbance, erectile dysfunction; less commonly hyperglycemia, depression, heart failure, heart block	Additive bradycardia with digoxin or nondihydropyridine CCBs; cardiodepressant effects with nondihydropyridine CCBs and amiodarone
Propranolol	Immediate-release: Initial 40-60 mg QID PO, usual 80-320 mg/day divided BID-QID Controlled-release: 60-320 mg/day PO once daily	Fatigue, hypotension, bradycardia, sleep disturbance, erectile dysfunction; more CNS effects (insomnia, vivid dreams) given high lipid solubility	Additive bradycardia with digoxin or nondihydropyridine CCBs; CYP2D6 inhibitors raise propranolol levels; raises rizatriptan levels	Immediate-release requires divided BID-QID dosing; controlled-release allows once-daily dosing.
Timolol	Initial: 10 mg PO BID Maximum: 30 mg PO BID	Fatigue, hypotension, bradycardia, sleep disturbance, erectile dysfunction	Additive bradycardia with digoxin or nondihydropyridine CCBs	Oral formulation not currently linked in the Pharmasist Drug Database (distinct from ophthalmic timolol).

Beta-blockers, selective (beta1)

Preferred over non-selective agents when fewer non-cardiac effects are desired. Same tapering and heart-block cautions as non-selective agents.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Atenolol	Initial: 25 mg/day PO Maximum: 200 mg/day, once daily or divided BID	Fatigue, hypotension, bradycardia, sleep disturbance, erectile dysfunction	Additive bradycardia with digoxin or nondihydropyridine CCBs
Bisoprolol	Initial: 2.5 mg once daily PO Maximum: 20 mg once daily	Fatigue, hypotension, bradycardia, sleep disturbance	Additive bradycardia with digoxin or nondihydropyridine CCBs
Metoprolol	Initial: 50 mg/day PO Maximum: 400 mg/day	Fatigue, hypotension, bradycardia, sleep disturbance, erectile dysfunction	Additive bradycardia with digoxin or nondihydropyridine CCBs; CYP2D6 inhibitors raise metoprolol levels	Regular-release requires divided BID dosing; sustained-release allows once-daily dosing.

Beta-blockers with intrinsic sympathomimetic activity

Considered specifically when a beta-blocker is desired in a patient with resting bradycardia — these agents lower resting heart rate less than agents without ISA.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Pindolol	Initial: 5 mg TID PO Maximum: 15 mg TID-QID	Fatigue, hypotension, bradycardia (less pronounced at rest than non-ISA agents), sleep disturbance	Additive bradycardia with digoxin or nondihydropyridine CCBs	Not currently linked in the Pharmasist Drug Database.
Acebutolol	Initial: 200 mg BID PO Maximum: 400 mg BID	Fatigue, hypotension, bradycardia (less pronounced at rest than non-ISA agents), sleep disturbance	Additive bradycardia with digoxin or nondihydropyridine CCBs	Not currently linked in the Pharmasist Drug Database.

Calcium channel blockers, dihydropyridine

Act primarily by arterial dilation; typically used as 2nd-line add-on to a beta-blocker. Amlodipine and nifedipine extended-release are Health Canada-approved for angina; felodipine has shown effectiveness in trials but does not carry a Health Canada angina indication and is not included here for that reason.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Amlodipine	Initial: 2.5 mg once daily PO Maximum: 10 mg once daily	Ankle edema, flushing, headache, hypotension, tachycardia	CYP3A4 substrate — strong inhibitors (azole antifungals, protease inhibitors, macrolides) raise levels; grapefruit may increase levels
Nifedipine, extended-release	Initial: 30 mg once daily PO Maximum: 120 mg once daily	Ankle edema, flushing, headache, hypotension, tachycardia	CYP3A4 substrate — strong inhibitors (azole antifungals, protease inhibitors, macrolides) raise levels; grapefruit may increase levels

Calcium channel blockers, nondihydropyridine

1st-line antianginal option, and preferred over a beta-blocker when vasospastic angina is suspected. Avoid in significant LV systolic dysfunction; use with caution in AV nodal disease.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Diltiazem	Initial: 120 mg/day PO Maximum: 360 mg/day	Headache, dizziness, bradycardia, heart block, new-onset or worsening heart failure, constipation	CYP3A4 substrate/inhibitor — many interactions; inhibits metabolism of carbamazepine, cyclosporine, lovastatin, simvastatin; additive negative inotropic effects with amiodarone, beta-blockers, digoxin	Use once-daily controlled/extended-release formulations.
Verapamil	Immediate-release: Initial 80 mg TID PO, maximum 160 mg TID Sustained-release: Initial 180 mg/day, maximum 480 mg/day	Headache, dizziness, bradycardia, heart block, new-onset or worsening heart failure, constipation	CYP3A4 substrate — many interactions; inhibits metabolism of carbamazepine, cyclosporine, lovastatin, simvastatin; increases digoxin levels by 50-75% within 1 week

Antiplatelet agents

ASA is first-line for essentially all patients; clopidogrel is reserved for ASA contraindication/intolerance in the absence of a recent ACS or stent. Ticagrelor's role in stable CAD is specifically for high-risk post-MI secondary prevention, not routine use.

Drug	Dosage	Adverse effects	Drug interactions	Comments
ASA	Maintenance: 80-160 mg PO once daily, indefinitely	Nausea, vomiting, gastritis, bleeding (epistaxis to major GI bleed), rash	Increased bleeding risk when combined with other antiplatelets or anticoagulants	Lower doses (80-160 mg/day) carry a lower serious GI bleeding risk than higher doses with comparable efficacy.
Clopidogrel	Maintenance: 75 mg PO once daily	Bleeding, diarrhea, rash	Increased bleeding risk when combined with other antiplatelets or anticoagulants; PPI use may reduce efficacy	Reserved for ASA contraindication/intolerance in stable CAD without a recent ACS or stent.
Ticagrelor (low dose)	Maintenance: 60 mg PO BID	Bleeding, dyspnea, bradycardia, gout-related side effects	Increased bleeding risk when combined with other antiplatelets or anticoagulants	Reserved for secondary MI prevention in high-risk patients, added to ASA, at least 1 year after MI — not a routine stable-angina option.

Dual-pathway antithrombotic therapy

An option in patients with stable CAD at elevated ischemic risk and acceptable bleeding risk, in addition to (not instead of) standard antiplatelet therapy — individualize given the trade-off between reduced ischemic events and increased bleeding.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Rivaroxaban (vascular dose) + ASA	Combo (adults): rivaroxaban 2.5 mg PO BID + ASA 100 mg PO once daily	Bleeding — more major bleeding than ASA alone, though no significant increase in intracranial or fatal bleeding	Increased bleeding risk when combined with other antiplatelets/anticoagulants; avoid strong dual CYP3A4/P-gp inhibitors or inducers	Individualize based on ischemic versus bleeding risk; not for routine use in every stable CAD patient.

Evidence: ^[10]

Lipid-lowering therapy

High-intensity statin for every patient with stable CAD regardless of baseline LDL, targeting LDL under 1.8 mmol/L (70 mg/dL) or at least a 50% reduction from baseline.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Atorvastatin (high-intensity)	Dosing: 40-80 mg PO daily	Myalgia, transaminase elevation	Diltiazem and other CYP3A4 inhibitors increase levels
Rosuvastatin (high-intensity)	Dosing: 20-40 mg PO daily	Myalgia, transaminase elevation	Fewer CYP3A4 interactions than atorvastatin
Ezetimibe	Dosing: 10 mg PO daily	Myalgia (mild), GI upset	None significant	Add if LDL remains ≥1.8 mmol/L (70 mg/dL) on maximally tolerated statin.
Evolocumab or alirocumab (PCSK9 inhibitor)	Dosing: Per current lipid-management dosing guidance	Injection-site reaction	None significant	Add if LDL remains ≥1.8 mmol/L (70 mg/dL) despite maximally tolerated statin plus ezetimibe.

ACE inhibitors / ARB

Indicated for stable CAD with a compelling indication (hypertension, diabetes, CKD, LV dysfunction), and reasonable to consider even without one given demonstrated benefit in broader high-risk populations.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Ramipril	Initial: 1.25-2.5 mg PO BID Target: 5 mg BID or 10 mg once daily	Cough, hyperkalemia, hypotension, rare angioedema	Hyperkalemia risk with potassium-sparing diuretics/spironolactone; avoid with lithium
Lisinopril	Initial: 2.5 mg PO daily Target: 20-40 mg daily	Cough, hyperkalemia, hypotension, rare angioedema	Hyperkalemia risk with potassium-sparing diuretics/spironolactone; avoid with lithium
Candesartan (ARB alternative)	Initial: 4-8 mg PO once daily Maximum: 32 mg once daily	Hyperkalemia, hypotension	Hyperkalemia risk with potassium-sparing diuretics/spironolactone	Use if an ACE inhibitor is not tolerated (e.g., cough).

Anti-inflammatory secondary prevention

Low-dose colchicine reduces the risk of MI, stroke, and the need for revascularization when added to standard secondary-prevention therapy in patients with established CAD; the 2024 ESC guideline upgraded this to a stronger recommendation on the basis of the LoDoCo2 trial.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Colchicine (low-dose)	Dosing: 0.5 mg PO once daily	GI upset (diarrhea, nausea) — usually dose-limiting	CYP3A4/P-glycoprotein interactions (e.g., clarithromycin, cyclosporine) can significantly raise levels	Consider in patients with established CAD already on standard secondary-prevention therapy; avoid in severe renal or hepatic impairment.

Evidence: ^[11]^[1]

Not available in Canada: nicorandil and trimetazidine are used for angina in some other countries but do not have Health Canada market authorization, so no Canadian dosing exists for either.

Evidence note: Drug inventory, dosing, adverse effects, and comments reflect standard Canadian practice, cross-checked against the current ESC and AHA/ACC chronic coronary disease guidelines.^[1]^[2]

References

2024 ESC Guidelines for the management of chronic coronary syndromes — European Heart Journal, European Society of Cardiology (Vrints C, Andreotti F, Koskinas KC, et al.). Eur Heart J 2024;45(36):3415-3537
2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease — Circulation, American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines (Virani SS, Newby LK, Arnold SV, et al.). Circulation 2023;148(9):e9-e119
Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease — New England Journal of Medicine (Diamond GA, Forrester JS). N Engl J Med 1979;300(24):1350-1358
Letter: Grading of angina pectoris — Circulation (Campeau L). Circulation 1976;54(3):522-523
Ivabradine in stable coronary artery disease without clinical heart failure — New England Journal of Medicine (Fox K, Ford I, Steg PG, et al., SIGNIFY investigators). N Engl J Med 2014;371(12):1091-1099
2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults — Canadian Journal of Cardiology (Pearson GJ, Thanassoulis G, Anderson TJ, et al.). Can J Cardiol 2021;37(8):1129-1150
Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients — New England Journal of Medicine (Yusuf S, Sleight P, Pogue J, et al., HOPE investigators). N Engl J Med 2000;342(3):145-153
Nitrate therapy for stable angina pectoris — New England Journal of Medicine (Parker JD, Parker JO). N Engl J Med 1998;338(8):520-531
Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial — JAMA (Chaitman BR, Pepine CJ, Parker JO, et al.). JAMA 2004;291(3):309-316
Rivaroxaban with or without aspirin in stable cardiovascular disease — New England Journal of Medicine (Eikelboom JW, Connolly SJ, Bosch J, et al., COMPASS investigators). N Engl J Med 2017;377(14):1319-1330
Colchicine in patients with chronic coronary disease — New England Journal of Medicine (Nidorf SM, Fiolet ATL, Mosterd A, et al., LoDoCo2 investigators). N Engl J Med 2020;383(19):1838-1847

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.