Contemporary Management of PAH
Selecting a treatment for PAH starts by determining the patient’s risk for disease progression. Low-risk patients are those who do not have right heart failure, rapidly progressive symptoms, or exertional syncope and are NYHA functional class 1 or 2, have a 6-minute walk distance of 440 meters (380 meters may be more reasonable), a normal brain-type natriuretic peptide (BNP) or NT-proB-type natriuretic peptide (NTBNP), only mildly reduced right ventricular function with no evidence of pericardial effusion on echocardiogram, and a preserved cardiac index (ideally at 2.5 liters/min/m2 or greater). High-risk patients are those with right heart failure, rapidly progressive symptoms, exertional syncope, NYHA functional class 4, have a 6-minute walk distance that is 165 meters or less, an elevated BNP, elevated right atrial size, elevated right atrial pressures, a pericardial effusion (which is a very poor prognostic indicator), and a low cardiac index. Patients who are between the high- and low-risk groups are considered to have intermediate risk.
One way to think of this is that it is not how high the mean pulmonary arterial pressure is, but how the heart is compensating, as reflected in the cardiac index and right atrial pressure.
Treatment goals can be different from the physician or the patient perspective. Most patients just want to feel better and live longer. From a medical perspective, that may mean improving functional class, quality of life, and survival. We measure these by looking at WHO functional class (aim for NYHA 1 or 2), 6-minute walk distance (aim for 380 to 440 meters), normal RV function, normal BNP, and favorable hemodynamics.
Although treatment guidelines are evolving (the most recent was from the European Respiratory Society in 2016), some standards remain constant: the need for PH to be confirmed by an expert, the need for a right heart catheterization, and the need to do an acute vasoreactivity test, when appropriate, to identify patients who will benefit from treatment with calcium channel blockers.
The FDA-approved PAH treatments include the phosphodiesterase type 5 inhibitors (sildenafil and tadalafil) and the soluble guanylate cyclase stimulator (riociguat), endothelin-receptor antagonists (bosentan, ambrisentan, and macitentan), and prostacyclin pathway medications (epoprostenol, treprostinil, iloprost, and selexipag).
Although the most recent treatment algorithm recommends initial monotherapy for low-risk patients, many practitioners start with oral combination therapy. For high-risk patients, the initial combination therapy usually includes a prostacyclin analogue. Parenteral prostacyclins are still the gold standard in high-risk patients because they have been proven to improve survival. Intermediate-risk patients are a harder group to treat. The primary determinant of treatment can be driven by right ventricular function and functional assessment. Many PH specialists are concerned that the availability and popularity of oral therapies will reduce referral of this particularly vulnerable population to PH specialty centers for assessment and treatment.
- Selecting a treatment for PAH starts by determining the patient’s risk of mortality and disease progression.
- Goals of treatment need to reflect the patient’s goals, which may just be to feel better and live longer.
- Diagnosis of PH needs to be confirmed by an expert who determines the performance of right heart catheterization and acute vasoreactivity testing before initiating therapy.
- The FDA-approved PAH treatments include sildenafil and tadalafil, the soluble guanylate cyclase stimulator (riociguat), endothelin-receptor antagonists (bosentan, ambrisentan, and macitentan), and prostacyclin pathway medications (epoprostenol, treprostinil, iloprost, and selexipag).
- Many specialists start low-risk patients on oral combination therapy rather than monotherapy.
- In high-risk patients, parenteral prostacyclins are still the therapeutic standard because they improve survival.
- Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119.
- McLaughlin VV, Gaine SP, Howard LS, et al. Treatment goals of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D73-81.
- McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-619.
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- Barst RJ, Rubin LJ, Long WA, et al; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296-301.
- Sitbon O, Humbert M, Jais X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005;111(23):3105-11.