Treatment of Patients with PH


Acute vasodilator testing to identify PAH patients who may benefit from chronic calcium-channel blocker (CCB) medications:

  1. Patients with Idiopathic, hereditary or drug and toxin-induced PAH should undergo acute vasodilator testing using a short-acting medication such as intravenous (IV) epoprostenol, IV adenosine, or inhaled nitric oxide (NO). A good response to acute vasodilator testing is defined as a fall in mean PAP of at least 10 mm Hg to 40 mm Hg, along with no change or an increase in cardiac output (CO).
    • Quality of evidence: fair
    • Recommendation: strong
  2. Patients with PAH associated with other medical conditions, such as scleroderma or congenital heart disease (CHD), may also undergo acute vasodilator testing.
    • Quality of evidence: no evidence
    • Recommendation: weak; based on the opinion of PH experts
  3. Acute vasodilator testing can be associated with significant risks. Patients with PAH should undergo acute vasodilator testing by a physician experienced in the management of PH.
    • Quality of evidence: no evidence
    • Recommendation: strong; based on the opinion of PH experts

 

Treatment of PAH patients with oral calcium-channel blockers (CCBs):

  1. A patient with Idiopathic PAH who does not have right ventricular (RV) failure but who demonstrates a good response to acute vasodilator testing, should be considered for a trial of treatment with oral calcium-channel blocker (CCB) tablets.
    • Quality of evidence: low
    • Recommendation: moderately strong
  2. A good response to acute vasodilator testing is very unusual in patients with PAH associated with other medical conditions, such as scleroderma or congenital heart disease. These PAH patients may also be considered for a trial of treatment with an oral calcium-channel blocker (CCB). Although these PAH patients may respond to oral CCBs, this is rare.
    • Quality of evidence: no evidence
    • Recommendation: moderately strong; based on the opinion of PH experts
  3. In patients with PAH who do not have a good response to acute vasodilator testing, CCBs should not be used to treat PH. As well, CCBs should not be used to treat PH in patients who have not undergone acute vasodilator testing. CCBs may increase the risk of death in such patients.
    • Quality of evidence: no evidence
    • Recommendation: strong; based on the opinion of PH experts

 

Treatment of PAH patients with Anticoagulants

  1. Patients with IPAH should be treated with the anticoagulant medication, warfarin.
    • Quality of evidence: fair
    • Recommendation: moderately strong
  2. In patients with PAH associated with other medical conditions, such as scleroderma or congenital heart disease (CHD), treatment with anticoagulant medication may be considered.
    • Quality of evidence: no evidence
    • Recommendation: weak; based on the opinion of PH experts

 

Treatment of PAH patients with Oxygen

  1. Some PAH patients may have low blood oxygen levels.
  2. In these PAH patients, treatment with supplemental or extra inhaled oxygen should be considered to keep blood oxygen levels >90% at all times.
    • Quality of evidence: no evidence
    • Recommendation: strong; based on the opinion of PH experts

 

Treatment of PAH patients in WHO functional class II

  1. In WHO class II PAH patients who have a good response to acute vasodilator testing, a trial of treatment with oral CCBs should be considered.
  2. In WHO class II PAH patients who do not have a good response to acute vasodilator testing, oral CCBs should not be used to treat PH.
  3. In WHO class II PAH patients who are not candidates for oral CCB treatment or who have already failed CCB treatment, treatment with oral sildenafil (Revatio) tablets should be considered. Alternatively, participation of these patients in clinical trials of new PH medications is encouraged.
    • Quality of evidence: no evidence
    • Recommendation: moderately strong based on the opinion of PH experts

More recently, recommendations from the 5th international Symposium on PH (Nice 2013) suggested that treatment with ambrisentan (Volibris), bosentan (Tracleer), macitentan (Opsumit), riociguat (Adempas), sildénafil (Revatio) ir tadalafil (Adcirca) are adequate options for WHO class II PAH patients who are not candidates for oral CCB treatment or who have already failed CCB treatment.

 

Treatment of PAH patients in WHO functional class III

  1. In WHO class III PAH patients who have a good response to acute vasodilator testing, a trial of treatment with oral CCBs should be considered.
  2. In WHO class III PAH patients who do not have a good response to acute vasodilator testing, oral CCBs should not be used to treat PH.
  3. In WHO class III PAH patients who are not candidates for oral CCB treatment or who have already failed CCB treatment, treatment with any of the following may be considered:
    1. Oral bosentan (Tracleer) tablets.
      • Quality of evidence: good
      • Recommendation: strong
    2. Oral sildenafil (Revatio) tablets.
      • Quality of evidence: good
      • Recommendation: strong
    3. Intravenous (IV) epoprostenol (Flolan, Caripul).
      • Quality of evidence: good
      • Recommendation: strong
    4. Subcutaneous (SC) treprostinil (Remodulin).
      • Quality of evidence: fair
      • Recommendation: moderately strong
    5. WHO class III PAH patients who do not qualify for or who do not respond to any of these treatments, should be considered for clinical trials of new PH medications.

More recently, recommendations from the 5th international Symposium on PH (Nice 2013) suggested that treatment with ambrisentan (Volibris), bosentan (Tracleer), macitentan (Opsumit), riociguat (Adempas), sildénafil (Revatio) ir tadalafil (Adcirca) are adequate options for WHO class III PAH patients who are not candidates for oral CCB treatment or who have already failed CCB treatment.

 

Treatment of PAH patients in WHO functional class IV

  1. WHO class IV PAH patients should generally not be treated with oral CCB tablets.
  2. In WHO class IV PAH patients, the first treatment of choice considered should be long-term IV epoprostenol (Flolan, Caripul).
    • Quality of evidence: good
    • Recommendation: strong
  3. In WHO class IV PAH patients, other treatments can also be considered:
    1. Oral bosentan (Tracleer) tablets.
      • Quality of evidence: fair
      • Recommendation: moderately strong
    2. Subcutaneous (SC) treprostinil (Remodulin).
      • Quality of evidence: fair
      • Recommendation: moderately strong
    3. WHO class IV PAH patients who do not qualify for or who do not respond to any of these treatments, should be considered for clinical trials of new PH medications.

 

Treatment of children with PAH

  1. In children with PAH, the general recommendations for medical treatments are similar to those in adults.
    • Quality of evidence: low
    • Recommendation: moderately strong
  2. Children with PAH should also be considered for treatment with oral anticoagulant medication, warfarin:
    1. Children with PAH and with right-ventricular (RV) failure should be treated with warfarin.
      • Quality of evidence: no evidence
      • Recommendation: moderately strong based on the opinion of PH experts
    2. Children with PAH but without RV failure may also treated with warfarin. For children < 5 years of age, a less intense degree of anticoagulation is recommended.
      • Quality of evidence: no evidence
      • Recommendation: weak based on the opinion of PH experts

 

Pregnancy in PAH patients

  1. In patients with PAH, pregnancy should be avoided, or abortion recommended.
    • Quality of evidence: good
    • Recommendation: strong