Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension

Heart. 2017 Apr;103(8):599-606. doi: 10.1136/heartjnl-2016-309621. Epub 2016 Dec 23.

Abstract

Objective: We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study.

Methods: Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo. Haemodynamic parameters were assessed at baseline and week 16.

Results: Riociguat decreased pulmonary vascular resistance (PVR) in inoperable (n=189; least-squares mean difference: -285 dyn s/cm5 (95% CI -357 to -213); p<0.0001) and persistent/recurrent (n=72; -131 dyn s/cm5 (95% CI -214 to -48); p=0.0025) patients. Cardiac index improved in inoperable patients by a least-squares mean difference of +0.6 L/min/m2 (95% CI 0.4 to 0.7; p<0.0001), while in persistent/recurrent patients the change was +0.2 L/min/m2 (95% CI -0.1 to 0.5; p=0.17). Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients(-4.7 mm Hg (95% CI -6.9 to -2.6; p<0.0001 and -4.8 mm Hg (-8.2 to -1.5; p=0.0055), respectively). For all patients, changes in 6 min walk distance correlated with changes in PVR (r=-0.29 (95% CI -0.41 to -0.17); p<0.0001) and cardiac index (r=0.23 (95% CI 0.10 to 0.35); p=0.0004).

Conclusions: Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH.

Trial registration number: NCT00855465.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Arterial Pressure / drug effects*
  • Chronic Disease
  • Double-Blind Method
  • Endarterectomy
  • Exercise Tolerance / drug effects
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Least-Squares Analysis
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiopathology
  • Pulmonary Embolism / complications*
  • Pulmonary Embolism / diagnosis
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Recovery of Function
  • Recurrence
  • Time Factors
  • Treatment Outcome
  • Vascular Resistance / drug effects*
  • Walk Test

Substances

  • Antihypertensive Agents
  • Pyrazoles
  • Pyrimidines
  • riociguat

Associated data

  • ClinicalTrials.gov/NCT00855465