In the past 15-20 years enormous progress has been made in the treatment of pulmonary arterial hypertension, one of the five subtypes of pulmonary hypertension (WHO group 1), with nine drugs approved by the EU regulatory authorities. The new treatments have led to significant improvements for patients in terms of symptoms, disease progression and survival. One of these nine drugs has shown benefits also in the form of pulmonary hypertension known as CTEPH (chronic thromboembolic pulmonary hypertension, WHO group 4). Currently there are no approved drugs for the other three classes of pulmonary hypertension.

Please scroll through the next sections for further details.

Further information and educational materials on PH therapies can also be found in the section ‘PH. It’s personal’ and drug information.

Approved drugs for pulmonary arterial hypertension fall under four main types:

1. Endothelin receptor antagonists (“ERA’s”)

These drugs aim to counterbalance the deleterious effects of endothelin, a substance which is thought to be produced in excess in PAH patients and which causes vaso-constriction (narrowing) of the blood vessels.

Three ERA’s are approved for use in PAH in Europe:

  • bosentan
  • macintentan
  • ambrisentan

ERA’s are oral drugs.

2. Phosphodiesterase type-5 (“PDE-5”) inhibitors

Inhibition of the PDE-5 enzyme results in vaso-dilatation through the nitric oxide pathway. In addition, PDE-5 inhibitors exert anti-proliferative effects.

Two PDE-5 inhibitors are approved for use in PAH in Europe:

  • sildenafil
  • tadalafil

PDE-5 inhibitors’s are oral drugs.

3. Prostanoids

Prostacyclin has very strong vasodilative effects on the blood vessels. In people with PAH an insufficient production of prostacyclin has been shown. The clinical use of prostacyclin has been made possible by synthetic analogues.

Four drugs targeting the prostacyclin pathway are currently approved in Europe:

  • selexipag
  • iloprost
  • treprostinil
  • epoprostenol

Drugs targeting the prostacycin pathway have different systems of delivery: oral (selexipag), inhaled (iloprost) and intravenous (epoprostenol), the latter two by 24/7 infusion with small portable pumps. In some countries the oral prostanoid beraprost is available as well as inhaled and intravenous treprostinil.

4. Soluble guanylate cyclase stimulators (SGCs)

Soluble guanylate cyclase stimulators help arteries relax to increase blood flow and decrease blood pressure. One soluble guanylate cyclase stimulator – riociguat – has been approved in Europe for two forms of pulmonary hypertension.

  • Riociguat is the first EMA approved treatment specifically for patients with CTEPH. It can be used for patients who have inoperable CTEPH and those with persistent or recurrent CTEPH following PEA (add hyperlink to section on CTEPH).
  • Riociguat is also indicated for patients with pulmonary arterial hypertension (PAH) of unknown causes, inherited or associated with connective tissue diseases, to improve their ability to exercise and to delay clinical worsening of their condition.

Riociguat is an oral drug.

Last updated: November 22, 2016