TY - JOUR
T1 - Successful Transition From Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension
T2 - A Pilot Cohort Study
AU - Kuroda, Kazuhiro
AU - Akagi, Satoshi
AU - Nakamura, Kazufumi
AU - Sarashina, Toshihiro
AU - Ejiri, Kentaro
AU - Ito, Hiroshi
N1 - Funding Information:
S. Akagi has received lecture fees from Actelion Pharmaceuticals Japan, AOP Orphan Pharmaceuticals, Bayer Yakuhin, and Nippon Shinyaku. K. Nakamura has received lecture fees from Actelion Pharmaceuticals Japan, AOP Orphan Pharmaceuticals, Bayer Yakuhin, Nippon Shinyaku, and Pfizer Japan. H. Ito has received lecture fees from Mochida Pharmaceutical and research grants from Mochida Pharmaceutical, Actelion Pharmaceuticals Japan, AOP Orphan Pharmaceuticals, Bayer Yakuhin, and Nippon Shinyaku. The other authors have no conflicts of interest.
Publisher Copyright:
© 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)
PY - 2020/3
Y1 - 2020/3
N2 - Background: Transition to pulmonary arterial hypertension (PAH)-specific drugs is considered in patients with PAH and chronic thromboembolic pulmonary hypertension who do not respond to combination therapy or who experience side effects to the combination drugs. Riociguat directly stimulates soluble guanylate cyclase independently of nitric oxide. Therefore, transition from a phosphodiesterase type 5 inhibitor (PDE5i), which requires nitric oxide to exert its effects, to riociguat might be effective. The length of time of washout periods for transition is important because haemodynamic instability sometimes occurs during these periods or during transition with no washout period. Method: We investigated the feasibility of transitioning from a PDE5i to riociguat without washout periods by monitoring haemodynamics under right heart catheterisation in six patients with PAH and one with chronic thromboembolic pulmonary hypertension who had already received dual- or triple-combination therapy. Results: Reasons for transition were headache caused by a PDE5i in three patients, and an inadequate response to combination therapy in four. Transition was successful in all patients, with no haemodynamic instability observed. Pulmonary vascular resistance (from 797 ± 241 to 518 ± 230 dyne/s/cm–5) and systemic blood pressure (from 121 ± 13 to 100 ± 15 mmHg) were significantly reduced immediately after transition. There were no significant differences in the tricuspid regurgitation pressure gradient or systemic blood pressure during the post-transition and follow-up periods. Headaches caused by a PDE5i were diminished after transition to riociguat. Conclusions: Transition from a PDE5i to riociguat without a washout period is safe. This transition may be a viable option for patients with headaches caused by a PDE5i, or who have an inadequate response to combination therapy that includes a PDE5i.
AB - Background: Transition to pulmonary arterial hypertension (PAH)-specific drugs is considered in patients with PAH and chronic thromboembolic pulmonary hypertension who do not respond to combination therapy or who experience side effects to the combination drugs. Riociguat directly stimulates soluble guanylate cyclase independently of nitric oxide. Therefore, transition from a phosphodiesterase type 5 inhibitor (PDE5i), which requires nitric oxide to exert its effects, to riociguat might be effective. The length of time of washout periods for transition is important because haemodynamic instability sometimes occurs during these periods or during transition with no washout period. Method: We investigated the feasibility of transitioning from a PDE5i to riociguat without washout periods by monitoring haemodynamics under right heart catheterisation in six patients with PAH and one with chronic thromboembolic pulmonary hypertension who had already received dual- or triple-combination therapy. Results: Reasons for transition were headache caused by a PDE5i in three patients, and an inadequate response to combination therapy in four. Transition was successful in all patients, with no haemodynamic instability observed. Pulmonary vascular resistance (from 797 ± 241 to 518 ± 230 dyne/s/cm–5) and systemic blood pressure (from 121 ± 13 to 100 ± 15 mmHg) were significantly reduced immediately after transition. There were no significant differences in the tricuspid regurgitation pressure gradient or systemic blood pressure during the post-transition and follow-up periods. Headaches caused by a PDE5i were diminished after transition to riociguat. Conclusions: Transition from a PDE5i to riociguat without a washout period is safe. This transition may be a viable option for patients with headaches caused by a PDE5i, or who have an inadequate response to combination therapy that includes a PDE5i.
KW - Pulmonary hypertension
KW - Sildenafil
KW - Soluble guanylate cyclase stimulator
KW - Tadalafil
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U2 - 10.1016/j.hlc.2019.01.013
DO - 10.1016/j.hlc.2019.01.013
M3 - Article
C2 - 30773322
AN - SCOPUS:85061454569
SN - 1443-9506
VL - 29
SP - 331
EP - 336
JO - Heart Lung and Circulation
JF - Heart Lung and Circulation
IS - 3
ER -