Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2

Ann Rheum Dis. 2017 Feb;76(2):422-426. doi: 10.1136/annrheumdis-2015-209087. Epub 2016 Jul 25.


Background: The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD).

Methods: Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability.

Results: In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population.

Conclusions: Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD.

Trial registration numbers: PATENT-1 (NCT00810693), PATENT-2 (NCT00863681).

Keywords: Arterial Hypertension; Systemic Lupus Erythematosus; Systemic Sclerosis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Connective Tissue Diseases / complications
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Male
  • Middle Aged
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Scleroderma, Systemic / complications*
  • Treatment Outcome
  • Vascular Resistance
  • Walk Test


  • Antihypertensive Agents
  • Pyrazoles
  • Pyrimidines
  • riociguat

Associated data