Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics

Int J Cardiol. 2018 Oct 15:269:283-288. doi: 10.1016/j.ijcard.2018.07.015. Epub 2018 Jul 3.

Abstract

Background: This study evaluated the incremental effect of riociguat on pulmonary hemodynamics in patients with inoperative or persistent chronic thromboembolic pulmonary hypertension (CTEPH) treated previously with sildenafil.

Methods: The retrospective study included 28 patients diagnosed with CTEPH who were ineligible for surgical treatment due to distal thrombi location or who suffered from persistent CTEPH after pulmonary endarterectomy and who were treated with sildenafil at a dose of 25 mg TID for a minimum of 3 months. Sildenafil was subsequently discontinued, and riociguat therapy was started with gradually increasing doses. Right heart catheterization was performed and WHO functional class (FC) was assessed in each patient at three time points: before starting sildenafil therapy (baseline), before the transition to riociguat, and after 3 to 6 months of therapy with riociguat.

Results: Compared to baseline, the use of sildenafil and riociguat significantly decreased pulmonary vascular resistance (PVR) (10.47 ± 3.56 vs. 7.81 ± 3.58 Wood units, p < 0.001) and mean pulmonary arterial pressure (PAP) (54.1 ± 11.6 vs. 46.1 ± 13.2 mm Hg; p < 0.001) while increasing cardiac output (CO) (4.31 ± 0.88 vs. 4.85 ± 0.87 L/min; p = 0.007). Switching from sildenafil to riociguat reduced PVR by 14% (p = 0.005) and the mean PAP by 6% (p = 0.03) while increasing CO by 11% (p = 0,002). The number of patients with WHO FC III and IV symptoms decreased from 71,4% to 57,1% (p = 0,02) after the change from sildenafil to riociguat.

Conclusions: Replacing sildenafil with riociguat in patients with inoperable or persistent CTEPH may improve pulmonary hemodynamics and FC.

Keywords: Chronic thromboembolic pulmonary hypertension; Hemodynamics; Riociguat; Sequential therapy; Sildenafil.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Drug Substitution / methods*
  • Enzyme Activators / administration & dosage
  • Female
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Lung / drug effects
  • Lung / physiology
  • Male
  • Middle Aged
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / physiopathology
  • Pyrazoles / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Retrospective Studies
  • Sildenafil Citrate / administration & dosage*
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage

Substances

  • Enzyme Activators
  • Pyrazoles
  • Pyrimidines
  • Vasodilator Agents
  • Sildenafil Citrate
  • riociguat