Successful Transition from Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study

Kazuhiro Kuroda, Satoshi Akagi, Kazufumi Nakamura, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Itoh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalHeart Lung and Circulation
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Phosphodiesterase 5 Inhibitors
Pulmonary Hypertension
Cohort Studies
Headache
Hemodynamics
Nitric Oxide
Blood Pressure
Tricuspid Valve Insufficiency
Drug Combinations
Therapeutics
Cardiac Catheterization
riociguat
Vascular Resistance
Pressure
Pharmaceutical Preparations

Keywords

  • Pulmonary hypertension
  • Sildenafil
  • Soluble guanylate cyclase stimulator
  • Tadalafil

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{8b9d51b5effc499e922fc1b0ffee3882,
title = "Successful Transition from Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study",
abstract = "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.",
keywords = "Pulmonary hypertension, Sildenafil, Soluble guanylate cyclase stimulator, Tadalafil",
author = "Kazuhiro Kuroda and Satoshi Akagi and Kazufumi Nakamura and Toshihiro Sarashina and Kentaro Ejiri and Hiroshi Itoh",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.hlc.2019.01.013",
language = "English",
journal = "Heart Lung and Circulation",
issn = "1443-9506",
publisher = "Wiley-Blackwell",

}

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 - Itoh, Hiroshi

PY - 2019/1/1

Y1 - 2019/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=85061454569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061454569&partnerID=8YFLogxK

U2 - 10.1016/j.hlc.2019.01.013

DO - 10.1016/j.hlc.2019.01.013

M3 - Article

AN - SCOPUS:85061454569

JO - Heart Lung and Circulation

JF - Heart Lung and Circulation

SN - 1443-9506

ER -