Stable Angina

Define angina. What is the difference between stable and unstable angina?

Angina - chest pain, pressure or discomfort usually caused by ischemia of the heart muscle

Stable angina - predictable chest pain, brought on by exertion or emotional stress, relieved within minutes by rest or short-acting nitroglycerin

Unstable angina (UA) - chest pain increases (in frequency, intensity or duration) and is NOT relieved with nitroglycerin or rest

Describe the pathophysiology of stable angina.

Angina = Oxygen demand > Oxygen supply

Demand increases with:

• ↑ Heart rate

• ↑ Contractility

• ↑ Preload

• ↑ Afterload

Supply decreases with:

• Coronary artery disease (atherosclerosis)

• Coronary artery vasospasm

  • Can occur at rest or caused by illicit drug use (cocaine)

What type of tests are used to diagnose stable angina and assess likelihood of CAD?

1) Cardiac stress test

• Increases myocardial oxygen demand with exercise or IV meds and monitors pt for sx of chest pain, SOB, lightheadedness, changes in HR/BP, ECG abnormalities

2) Coronary angiography

• Performed to assess the extent of atherosclerosis and need for revascularization

Describe the treatment approach for stable angina.

1) Antiplatelet (for secondary prevention)

• Aspirin - recommended antiplatelet

• Clopidogrel used when there is allergy or CI to aspirin

• DAPT NOT useful for secondary prevention in pts with stable angina

  • Recommended only after recent ACS or percutaneous coronary intervention (PCI)

2) Antianginal (reduce chest pain)

3) BB, DHP / non-DHP CCB, long-acting nitrates

• Prevent symptoms

4) Ranolazine can be added if needed after above therapies

5) Short-acting nitroglycerin (SL) or TL spray

• Recommended for immediate relief of angina in ALL pts

Aspirin MOA

Irreversibly inhibits COX-1 and COX-2 enzymes —> ↓ prostaglandin (PG) and thromboxane A2 (TXA2) production

• TXA2 is a potent vasoconstrictor and inducer of platelet aggregation

Aspirin CI

NSAID or salicylate allergy

Children and teenagers with viral infection (due to risk of Reye’s syndrome) - sx of somnolence, N/V, and confusion

Aspirin warnings / SEs/ monitoring

Warnings

• Bleeding

• Tinnitus (a sign of salicylate overdose)

SEs

• Dyspepsia, heartburn, bleeding, nausea

Monitoring

• Sx of bleeding, bruising

How long does a pt have to be on aspirin when used for stable angina? Why?

Used indefinitely in stable angina: ↓ CV events and death

What form of aspirin is preferred in ACS?

• Non-enteric coated, chewable aspirin

• If only enteric-coated aspirin availble, should be chewed (325mg)

What drug can be used to protect the GI tract from chronic aspirin use?

PPIs

• Consider risk vs benefits

  • Risks: ↓bone density, ↑infection risk

Clopidogrel MOA

Prodrug that irreversibly inhiits P2Y12 ADP-mediated platelet activation and aggregation

Clopidogrel boxed warning

Prodrug

• Effectiveness depends on conversion to active metabolite via CYP450 2C19

  • If poor metabolizer, consider other treatments

Clopidogrel CI / warnings/ SEs/ monitoring

CI

• Serious bleeding (GI bleed, intracranial hemorrhage)

Warnings

• Bleeding risk

• DO NOT use with omeprazole or esomeprazole

  • Omeprazole/esomeprazole: CYP2C19 inhibitors

• Premature discontinuation (↑ risk of thrombosis)

• Thrombotic thrombocytopenia purpura (TTP)

  • Small blood clots forming in many small blood vessels throughout the body

SEs

• Bleeding

Monitoring

• Symptoms of bleeding, Hgb/Hct as necessary

Clinical benefit of beta blockers as antianginal treatment.

Reduce oxygen demand from heart: ↓ HR, ↓ contractility, ↓left ventricular wall tension

In what type of angina should BB be avoided?

Avoid in vasospastic angina

• Use CCB instead

Clinical benefit of CCB as antianginal treatment

• Reduce myocardial oxygen demand: non-DHPs ↓ HR and contractility; DHPs ↓ SVR (afterload)

• Slow release/long acting preferred

  • AVOID nifedipine IR

• DHPs preferred when used with BB compared to non-DHPs

  • Risk of bradycardia

Clinical benefit of nitrates as antianginal treatment

• ↓ preload (free radical nitric oxide produces vasodilation of veins more than arteries)

• Fast relief for chest pain

Nitrate CI

Do not use with PDE-5 inhibitors

Nitrate warnings / SE/ monitoring

Warnings

• Hypotension

• Tachyphylaxis (tolerance/↓effectiveness)

SE

• HA, flushing, syncope, dizziness

Monitoring

• BP, HR, chest pain

Long acting nitrates require a nitrate free interval. Why? How long is patch, ointment, and isosorbide mononitrate dosed?

Ranolazine MOA

Selectively inhibits late phase Na current and ↓ intracellular Ca

• ↓ ventricular tension

Ranolazine CI / warnings / SEs/ monitoring

CI

• Liver cirrhosis; don’t use with strong CYP3A4 inhibitors or inducers

Warnings

• QT prolongation

• Acute renal failure observed when CLcr < 30 mL/min

SEs

• Dizziness, HA, constipation, nausea

Monitoring

• ECG, K, renal function

What is the major drug interaction with ranolazine?

Ranolazine is a major CYP3A4 substrate and minor CYP2D6 and pgp substrate

• DO NOT use with strong CYP3A4 inhibitors or inducers