RIOCIGUAT IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION AND SEVERE RENAL IMPAIRMENT

Abstract

Objective: To demonstrate the efficiency and safety of using riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and severe renal impairment with creatinine clearance (CrCL) <15 ml/min. Design and method: A 51-year old female was admitted to pulmonary hypertension department with shortness of breath during minimal exertion and cough. At the age of 37 she underwent allogeneic kidney transplantation due to terminal renal impairment, which developed as a result of chronic glomerulonephritis. Nephropathy of transplanted kidney progressed within following 3 years to creatinine level 350–400 μmol/l. At the age of 49 the patient had pulmonary embolism. After 1 year of anticoagulation therapy there was diagnosed CTEPH, WHO-FC III. Due to severity of renal impairment thrombendarterectomy and balloon pulmonary angioplasty weren’t performed. In department echocardiography showed increased systolic pulmonary artery pressure (PAP) (80 mmHg), mean PAP (44 mmHg). 6-minute walking distance (6MWD) was 360 m. Right heart catheterization and angiopulmonography were not performed due to the high risk of worsening of renal function. The patient was administered riociguat 0.5 mg with gradual increase to 1 mg 3 times a day. Because the product label states, that patients with renal impairment have increased riociguat exposure, daily dose wasn’t enlarged more. Results: After 2 weeks with riociguat we revealed disappearance of cough, increased physical activity (6MWD 416 m), decreased systolic and mean PAP (72 and 41 mmHg). In control blood tests there were no signs of renal function worsening: creatinine before treatment 356 vs after 387 μmol/l, CrCL by Cockroft-Golt – 14 vs 13 ml/min, urea – 18.4 vs 20.3 mmol/l. At 6 months follow-up we observed further reduction of systolic and mean PAP (67 and 39 mmHg), increase of 6MWD (430 m). The sings of renal impairment were at the same level: creatinine 385 μmol/l, CrCL 13 ml/min, urea 21.9 mmol/l. Conclusions: The administration of riociguat for patients with CTEPH and severe renal impairment with CrCL <15 ml/min can be effective and safe, if provided strict control of renal function and carefully adjusted dose.