PAH Bates

How is pulmonary arterial hypertension (PAH) defined?

mPAP ≥ 20 mmHg at rest + PCWP ≤ 15 mmHg + PVR > 3 Wood units

Which drugs definitively cause PAH?

Anorexigens (weight loss drugs): aminorex, fenfluramine, benfluorex, dexfenfluramine, phentermine

Which drugs are likely/possible causes of PAH?

Amphetamines, cocaine, leflunomide, chemotherapy (bleomycin, cyclophosphamide)

What are the 5 WHO groups of pulmonary hypertension?

1. PAH (Group I)

2. Left heart disease

3. Lung disease

4. CTEPH (chronic thromboembolic PH)

5. Unknown causes

What is Class I PAH?

No limitation of physical activity

What is Class II PAH?

Mild limitation; no symptoms at rest, symptoms with normal activity

What is Class III PAH?

A: Marked limitation; no symptoms at rest, symptoms with less-than-normal activity

What is Class IV PAH?

Symptoms at rest; unable to do any physical activity

Symptoms of PAH?

DYSPENIA ON EXERTION, Fatigue, weakness, exercise intolerance, chest pain, dyspnea at rest (late), edema, abdominal distension

What is used initially to evaluate PAH?

Echocardiogram

What does the 6MWT measure and what does it reflect?

Distance walked in 6 minutes and submaximal exercise capacity

What is the gold standard test for PAH?

Right heart catheterization, it confirms diagnosis

What is the purpose of vasoreactivity testing in PAH?

To determine if patients are candidates for CCB therapy, if POSITIVE give CCB

What is the goal oxygen saturation in PAH patients?

>90 at rest

What anticoagulant is preferred in PAH supportive therapy?

Warfarin (INR 1.5-2.5)

Which type of CCBs are preferred? and examples

Dihydropyridines, Nifedipine ER, amlodipine

Which non-DHP CCB can be used and what type of pt?

Diltiazem for tachycardic pts, VERAPIMIL NEVER USED

When should treatment response with CCBs be reassessed?

after 3-4 months

What drugs are contraindicated with sildenafil?

Nitrates or riociguat → severe hypotension

What drug interaction requires caution with sildenafil?

Bosentan (CYP3A4 inducer)

What are contraindications and DI for tadalafil?

Nitrates or riociguat, DI with Bosentan

What drugs are ERAs?

Ambrisentan, Macitentan, Bosentan

What is the boxed warning/CI for ERAs? and how are they distributed

Teratogenic (harm to fetus), REMs program

Key warnings of ERAs?

Hepatotoxicity, ↓Hgb/Hct, fluid retention

What is the boxed warning for bosentan?

Hepatotoxicity

Are other ERAs preferred over bosentan?

Yes

Common side effects of ERAs?

Edema, upper respiratory infections

Name Prostacyclin Analogues

Epoprostenol, Iloprost, Treprostinil

What happens if therapy is stopped suddenly with prostacyclin analogues?

Rebound pulmonary hypertension

What is a major risk with chronic IV therapy with prostacyclin analogues?

Sepsis / bloodstream infections

How is epoprostenol administered?

Continuous IV infusion (central line)

Key benefit of epoprostenol?

Survival benefit

What is the route of administration for iloprost?

Inhalation

MOA Selexipag?

Selective IP receptor antagonist

When is selexipag used?

As a 3rd agent in patients on dual therapy

What routes are available for Selexipag?

IV and oral

What to do if therapy is interrupted for 3 days on Selexipag?

Restart at lower dose and re-titrate

What is the boxed warning for riociguat? and what program is required?

Teratogenic, Rems

Contraindications of riociguat?

Pregnancy, use with PDE-5 inhibitors or nitrates

Management of WHO Functional Class I PAH?

• No pharmacotherapy

• Lifestyle: smoking cessation, low sodium, exercise

• Observation

• Monitor 6MWD and echo

Initial management of WHO Class II PAH?

• Vasoreactivity testing → CCB if positive

• If negative:

  • Oral therapy (PDE5i, ERA, riociguat)

Preferred therapy for WHO Class II PAH?

• Combination therapy preferred

• Ambrisentan + tadalafil

Management of WHO Class III PAH?

• Ambrisentan + tadalafil still preferred

• Other combos possible (ERA + riociguat)

• If worsening/rapid progression:

  • Prostacyclins (IV epoprostenol, inhaled iloprost, treprostinil)

Management of WHO Class IV PAH?

• IV prostacyclin (epoprostenol) = FIRST-LINE

• Consider triple therapy (ERA + PDE5i + prostacyclin)

• If failure → lung transplant

• CCBs rarely used

Name the 2 classes that have CI with Pregnancy

ERA + Ricougat