TABLE 1

Overview of the effects of riociguat on the right ventricle in clinical studies

Study designRiociguat treatmentChanges to the right ventricle following riociguat treatment compared with baseline#Reference
Retrospective single-centre study of 39 patients with PH (21 PAH, 18 CTEPH) in PATENT-1, PATENT-2, PATENT PLUS, CHEST-1, CHEST-2 or CTEPH Early Access Study (EAS)1.0–2.5 mg three times daily for 3–12 monthsFunction
  • Increased TAPSE at 6 months (p=0.025) and 12 months (p=0.002)

  • Increased tricuspid annular velocity at 12 months (p=0.006)

  • Decreased systolic PA pressure and mPAP at 3 months (both p=0.03)

  • Increased CO and CI at 3 months (both p<0.001)

  • Decreased PVR at 3 months (p<0.001)

Size
  • Decreased RV area at 3 months (p=0.002), 6 months and 12 months (both p<0.001)

  • Decreased RA area at 6 months (p=0.06) and 12 months (p<0.001)

  • Decreased RV free wall thickness at 3 months (p<0.05), 6 months and 12 months (both p<0.01)

Other remodelling
  • Improved RV remodelling at 6 months (p=0.003) and 12 months (p=0.03)

[35]
Retrospective multicentre study of 71 patients with PH (32 PAH, 39 CTEPH) in phase II, PATENT-1, PATENT-2, PATENT PLUS, CHEST-1, CHEST-2 or CTEPH EAS (RIVER study)1.0–2.5 mg three times daily for 3–12 monthsFunction
  • Improved RV systolic function at 12 months (p=0.016)

  • Increased TAPSE at 12 months (p<0.001)

  • Decreased tricuspid regurgitation velocity at 12 months (p=0.005)

  • RV fractional area change at 12 months (p<0.001)

Size
  • Decreased RV area at 3 months, 6 months and 12 months (all p<0.001)

  • Decreased RA area at 6 months and 12 months (both p<0.001)

  • Decreased RV thickness at 12 months (p=0.023)

Other remodelling
  • Decreased PA diameter at 12 months (p=0.014)

[36]
Retrospective study of 27 patients with PH (7 PAH, 20 CTEPH)Mean dose of 7.3±0.7 mg administered for a mean 220 daysFunction
  • Increased RV fractional area change (p=0.005)

  • Decreased RV global longitudinal strain (p=0.0006)

Size
  • Decreased basal, mid and longitudinal RV diameters (all p=0.001)

  • Decreased RV end-diastolic area index (p=0.0005)

[37]
Retrospective analysis of 45 patients with PH (14 PAH, 31 CTEPH)Mean final daily dose of 7.2±0.9 mg administered for a mean 234 daysFunction
  • Decreased mPAP (p=0.008)

  • Increased CI (p=0.04)

  • Decreased PVR (p=0.016)

  • Increased RV systolic excursion velocity (p=0.001)

  • Decreased RV global longitudinal strain (p<0.001)

  • Increased fractional area change (p<0.001)

  • Decreased RV dyssynchrony index (p=0.012)

  • Decreased estimated PA systolic pressure (p<0.001)

  • Decreased tricuspid regurgitation pressure gradient (p<0.001)

Size
  • Decreased RV basal (p<0.001), mid (p<0.001) and longitudinal (p=0.002) diameters

  • Decreased RV end-diastolic and end-systolic area indices (p<0.001)

  • Decreased RA area index (p=0.0014)

[38]
Post hoc analysis of 341 patients with PAH in PATENT-1 and 238 patients with CTEPH in CHEST-1Up to 2.5 mg three times daily for 12 weeks for PATENT-1 and 16 weeks for CHEST-1Function compared with placebo treated
  • Increased stroke volume, SVI and cardiac efficiency in PATENT-1 and CHEST-1 (all p<0.0001)

  • Increased RV work in PATENT-1 (p=0.0002) and CHEST-1 (p=0.0317)

  • Increased RV work index in PATENT-1 (p<0.0001) and CHEST-1 (p=0.0338)

  • Increased RV power in PATENT-1 (p=0.0002) and CHEST-1 (p=0.0317)

  • Decreased PA elastance in PATENT-1 and CHEST-1 (both p<0.0001)

[39]
Single-centre prospective randomised open-label trial of 21 patients with CTEPH who had mPAP <30 mmHg after undergoing BPAUp to 2.5 mg three times daily for 6 months (8 of the 10 patients in the riociguat arm received less than the maximum dose)Function at peak workload compared with standard of care treated
  • Increased CO and decreased PVR at 6 months (both p<0.01)

  • Trend of improved mPAP–CO slope at 6 months (p=0.09)

[40]
Post hoc analysis of the RESPITE study in 61 patients with PAH1.0–2.5 mg three times daily for 24 weeks following a 1–3-day PDE5i treatment-free periodFunction following switch
  • Increased cardiac efficiency (p=0.0004)

  • Increased stroke volume (p=0.0044)

  • Increased SVI (p=0.0052)

  • Maintained RV work (p=0.1770)

  • Maintained RV work index (p=0.0793)

  • Maintained RV power (p=0.1770)

  • Maintained PA elastance (p=0.0888)

[41]
Retrospective analysis of 28 patients with CTEPH who were switched from sildenafil to riociguatUp to 2.5 mg three times daily for a median follow-up time of 5.8 (3.6–7.9) months following switchingFunction following switch
  • Decreased PVR (p=0.005)

  • Decreased systemic vascular resistance (p=0.001)

  • Decreased mPAP (p=0.03)

  • Increased CO (p=0.002)

[42]
Single-centre retrospective analysis of 26 patients with PAH receiving triple therapy with riociguat, macitentan and selexipagOf 26 patients, 24 received riociguat up-titrated to maximum tolerated dose for a median observation period of 441 daysFunction
  • Decreased mean RA pressure (p=0.005)

  • Decreased mPAP (p<0.001)

  • Increased CO (p<0.001)

  • Increased CI (p<0.001)

  • Decreased PVR (p<0.001)

  • Increased TAPSE (p=0.001)

  • Increased RV systolic excursion velocity (p=0.001)

  • Increased fractional area change (p<0.001)

Size
  • Decreased RV end-systolic area (p=0.006)

[43]
Prospective study of 6 patients with CTEPH0.5–2.5 mg three times daily for 6 monthsFunction
  • Increased RV SVI (p=0.03)

  • Trend of increased RV ejection fraction (p=0.09)

Other remodelling
  • Trend of decreased myocardial fibrosis volume and mass (both p=0.09)

[44]
Single-site pilot study of 20 patients with PAH (12 treatment-naïve patients and 8 who were switched from sildenafil to riociguat)1.0–2.5 mg three times daily for 12 weeksFunction
  • Decreased systolic PA pressure (p=0.003)

  • Decreased mPAP (p=0.007)

  • Increased RV fractional area change (p=0.04)

  • Decreased RV end-diastolic volume (p=0.003)

  • Decreased RV end-systolic volume (p=0.002)

Size
  • Decreased RV basal diameter in treatment-naïve patients only (p=0.03); not significant in switched patients

Other remodelling
  • Decreased RV–PA coupling (p=0.02)

[45]

RV: right ventricular; PH: pulmonary hypertension; PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; TAPSE: tricuspid annular plane systolic excursion; PA: pulmonary artery; mPAP: mean pulmonary arterial pressure; CO: cardiac output; CI: cardiac index; PVR: pulmonary vascular resistance; RA: right atrial; BPA: balloon pulmonary angioplasty; PDE5i: phosphodiesterase-5 inhibitors; SVI: stroke volume index. #: outcomes compared with baseline unless otherwise stated.