CTEPH: medical treatment
Riociguat has a dual mode of action: it increases the sensitivity of sGC to endogenous bioavailable nitric oxide (NO) by stabilising the NO-sGC binding and stimulates directly sGC
independently of NO. Oral administration of riociguat results in an increase of cGMP with antifibrotic (vascular remodelling) and vasodilating effects. The most recent and largest RCT of medical treatment in CTEPH to date is the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial-1), including 261 patients of whom 27% had post-operative residual or persistent PH after PEA.20
Patients were randomised to
receive either placebo or riociguat and were studied for 16 weeks. The six minute walk distance increased from baseline by a mean of 39m in the riociguat group (95% confidence interval: 25 to 67; p<0.001). PVR decreased by 226 dyn.se
c. cm-5 in the riociguat group (95% confidence interval: –303 to –190; p<0.001). Riociguat therapy was also associated with significant improvements in NT-proBNP level (p<0.001) and WHO functional class (p=0.003). This study became the first to show significant clinical efficacy in CTEPH and was pivotal for the approval by the US Food and Drug Administration and by the European Medical Agency for the treatment of patients with inoperable or persistent/ recurrent pulmonary hypertension after PEA.
Other treatment options In select inoperable cases, or after PEA failure, lung transplantation could be considered.
Balloon pulmonary angioplasty, a technique developed in Japan, could become a potential promising alternative for inoperable patients but needs further validation.21
(Figure 1) Conclusions
Once CTEPH is diagnosed, all patients should receive life-long anticoagulation therapy unless contra-indicated. The standard and potentially curative treatment for CTEPH is PEA, a surgical procedure in which the pulmonary blood vessels are cleared of obstructive material. Therefore all CTEPH patients should be evaluated for operability by an experienced CTEPH team.
If a patient is considered inoperable by an experienced CTEPH team, a second
“Riociguat is the first, and so far only, drug to demonstrate significant clinical efficacy in patients with inoperable CTEPH or persistent/ recurrent CTEPH after pulmonary endarterectomy and has been approved by the EMA and FDA”
In select cases lung transplantation could be considered. Balloon pulmonary angioplasty, a technique developed in Japan, could become a potential promising alternative but further studies are required.21 l
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opinion is recommended.
For inoperable patients, or patients with persistent pulmonary hypertension after pulmonary endarterectomy, medical treatment is recommended. Several open-label and randomised controlled trials of three to six months duration have reported different degrees of efficacy with medical treatment. Riociguat is the first and so far only drug to demonstrate significant clinical efficacy in patients with inoperable CTEPH or persistent/ recurrent CTEPH after pulmonary endarterectomy and has been recently approved by the American Food and Drug Administration and European Medical Agency.
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