This document summarizes the management of pulmonary artery hypertension. It discusses general measures, classes of medical therapy including diuretics, anticoagulants, calcium channel blockers, endothelin receptor antagonists, phosphodiesterase inhibitors, prostacyclins, and guanylate cyclase stimulators. It also discusses surgical therapies like atrial septostomy and indications for lung transplantation. The various medications are described in terms of their effects, dosing, and side effects. Large clinical trials on combination therapy are also summarized.

1. MANAGEMENT OF
PULMONARY ARTERY
HYPERTENSION
Anuj Mehta

2. Vallerie V. McLaughlin et al. JACC 2015;65:1976-1997American College of Cardiology Foundation

3. General measures
• Low-level graded aerobic exercise, such as walking.
• Avoid heavy physical exertion and isometric exercise, as this may evoke exertional
syncope.
• Oxygen supplementation - SpO2> 90% at rest and with exertion, sleep, or altitude.
• A sodium-restricted diet - manage volume status in those with RV failure.
• Routine immunizations, such as those against influenza and pneumococcal
pneumonia.

4. Classes of therapy
• MEDICAL
• Diuretics
• Anti coagulants
• Digoxin
• Oxygen
• PAH specific therapy
• SURGICAL THERAPY
• Atrial septostomy
• Lung transplantation

5. Diuretics
• To manage RV volume overload
• Serum electrolytes and renal function to be
monitored
• May need to combine Thiazide and loop
diuretics.

6. Anticoagulants
• Studies show improved survival primarily in IPAH.
• INR- 1.5- 2.5
• decreases chances of in-situ thrombosis.

7. Oxygen
• assessment of nocturnal and exertion
oxygenation requirement.
• minimises added insult of hypoxic
vasoconstriction.
• maintain SpO2 > 90%
• rule out concomitant OSA

8. PAH Specific Therapies
• Calcium Channel Blockers
• Endothelin Receptor Antagonist(ERAs)-Bosentan,
Sitaxsentan, Ambrisentan
• PhosphodiesteraseV Inhibitors (PDE 5-I)- Sildenafil, Tadalafil,
Vardenafil.
• Prostacyclins - Epoprostenol, Treprostinil,Iloprost
• Guanylate cyclase stimulators - Riociguat

10. Calcium channel blockers
• Used only when - acute response to vasodilator
testing is demonstrated. (10%)
• Long acting- Diltiazem , nifedipine , amlodipine
• Verapamil avoided- negative inotropic effect
• only 50% maintain response to CCB
• Not in Class IV or patients haveng severe right heart
failure.
• S/E- systemic hypotension

11. ERAs
• Targets relative excess of Endothelin -1
• Blocks ER on endothelium and vascular smooth muscle
• Bosentan, Macitentan (ER-A & B), Ambrisentan (ER-A)
• Improvement in 6 MWD and time to clinical worsening.
• In Eisenmenger physiology- improvement in PVR, mPAP, 6
MWD.
• Bosentan- Requires LFT monitoring.(rarely - cirrhosis)
• Macitentan- increased tissue penetration & sustained blockade

12. • Oral dosing- Bosentan
• Initiate at 62.5 mg BID X 4 weeks( >12 years,
> 40 kg.)
• increase to maintainance - 125 mg BID
• NO dose adjustment for renal impairment
• No dose adjustment for concomitant
anticoagulation.

13. Ambrisentan
• 5 to 10 mg once daily
• low hepatic toxicity
• No dose adjustment for anticoagulation.

14. PDE 5 I
• Nitric oxide exerts effect through cGMP pathway
and is modulated by PDEs.
• PDE5 is located in walls of blood vessels.
• Pulmonary vasculature has predominantly PDE-
5.
• Sildenafil-Improves 6MWD , but not time to
clinical worsening.
• Tadalafil- improves 6MWD and time to clinical
worsening.

15. • Dose -
• Sildenafil 20 mg TID (0.5 mg/ kg TDS)
• I.V.- Loading 0.4 mg/kg over 3 hours —> 0.07
mg/kg/hr
• Tadalafil 40 mg OD
• Vardenafil 5 mg OD
• S/E- headache, Epistaxis, hypotension, sudden
hearing loss.

16. Prostacyclin analogues
• Prostacyclin synthase expression is reduced in
endothelial cells in PAH
• Epoprostenol , treprostinil , iloprost
• Benefits
• vasodilator
• platelet inhibition
• anti-proliferative effects
• inotropic effects

17. Epoprostenol
• First FDA approved PAH specific therapy
• improved 6MWD , hammedynamics . QoL and survival
• Very short half life- 2 minutes
• Delivered via continuous I.V. infusion
• 2 ng/kg/min (25to 40 ng/kg/min)
• S/E- jaw pain, flushing, nausea, musculoskeletaletal
pain.
• Catheter complications- dislodgement, embolization,
infection.

18. Treprostinil
• Continuous subcutaneous/ i.v. infusion or
intermittent inhaled treatment.
• t 1/2 - 4 hours
• less risk of rapid fatal deterioration if infusion
stops.
• Lesser catheter related complicateons
• increased gram negative blood stream
infections.

19. Iloprost
• Inhaled prostacyclin
• administered 6-9 times via nebuliser
• S/E : morning syncope, interaction with other
anti hypertensives, increased bleeding with
anticoagulation.
• Nausea vomiting,
• elevated liver enzymes.

20. Soluble Guanylate cyclase
stimulators
• Stimulate nitric oxide receptor
• Dual mode of action
• increases sensitivity of sGC to endogenous
NO
• directly stimulate receptor to mimic NO
• Ricociguat- oral , inoperable CTEPH.

21. COMPASS Program
• Combination of Bosentan and Sildenafil Versus
Sildenafil Monotherapy on Pulmonary Arterial
Hypertension
• Largest RCT for PAH
• morbidity and mortality trial
• assessed safety of bosentan and sildenafil.
• Comprehensive trial to lead the future management of
PAH
• Adding bosentanan to stable silkenafil therapy - no
added advantage.

23. Failure of medical therapy: Atrial
septostomy
• Improved left sided filling
• Decreased right sided pressures
• Bridge to transplant

24. Failure of medical therapy :
indications for lung transplant
• NYHA classs III or IV
• Mean right atrial pressure > 10 mmHg
• Mean pulmonary arterial pressure > 50 mm Hg
• Failure to improve functionally.
• Rapidly progressive disease.

25. Vallerie V. McLaughlin et al. JACC 2015;65:1976-1997American College of Cardiology Foundation