Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular–Pulmonary Arterial Coupling

Abstract

PurposeTo evaluate the influence of riociguat on World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling, and right ventricular–pulmonary arterial (RV–PA) coupling in patients with idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naïve or who have failed to achieve treatment goals with sildenafil therapy.MethodsTwenty patients with IPAH were enrolled: 12 had not previously received PAH-targeted therapy (treatment-naïve subgroup) and 8 had been receiving sildenafil therapy but failed to achieve treatment goals; on entering this pilot study these 8 patients were switched from sildenafil to riociguat therapy (treatment-switch subgroup). Patients received riociguat individually dose-adjusted up to a maximum of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC, 6MWD, right heart remodeling, and RV–PA coupling.ResultsRiociguat significantly improved WHO FC in treatment-naïve patients (from 0/4/8/0 patients in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week 12). Additionally, treatment-naïve and treatment-switch patients showed significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8 m and + 71.6 m, respectively), RV systolic function, and RV–PA coupling.ConclusionThese results support the proven efficacy of riociguat in patients with IPAH, including treatment-naïve patients and those switching to riociguat following failure to achieve treatment goals with sildenafil, and suggest that it may be possible to delay disease progression in this patient group.Electronic supplementary materialThe online version of this article (10.1007/s00408-018-0160-4) contains supplementary material, which is available to authorized users.

A focus on riociguat in the treatment of pulmonary arterial hypertension

“…A small pilot study of 20 patients with PAH either treatment naive or with insufficient response to sildenafil switched to riociguat has furthermore shown positive results, with significant improvement in 6MWD of +71.6 ( P = 0.03) and WHO FC ( P = 0.02) . The results reveal that patients with insufficient treatment response to PDE‐5 inhibitors might benefit from changing to riociguat and indicate that riociguat could be superior to PDE‐5 inhibitors in a patient group, where endogenous NO production might be insufficient.…”

Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

“…Thus, prevention or reverse of pulmonary vascular remodeling, which brings the decrease of pulmonary artery pressure, is considered the priority for PAH therapy. Besides intervention of pulmonary arteries, accumulating evidence suggests that directly targeting the RV with the aim of supporting and protecting the right side of the heart also possesses the potential to improve cardiac function in patients or animals with PAH [24,25]. During the development of PAH, multiple mechanisms are believed to be responsible for the right ventricular remodeling in response to the chronically elevated pulmonary artery pressure.…”

The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: focus on the stimulator of soluble guanylate cyclase riociguat

“…Кроме того, все пациенты показали значительный прирост Д6МХ к 12-й неделе по сравнению с исходным уровнем (+76,8 м и +71,6 м соответственно), улучшение систолической функции ПЖ и сердечно-сосудистого сопряжения ПЖ и ЛА. Таким образом, первые результаты подтвердили доказанную эффективность риоцигуата как у пациентов с ИЛГ, ранее не получавших специфические препараты, так и у пациентов после переключения с силденафила на риоцигуат в связи с неэффективностью предшествующего лечения и недостижением целей терапии [39]. В дальнейшем группа данного проспективного исследования была увеличена до 24 пациентов: 20 -с ИЛГ и 4 -с неоперабельной ХТЭЛГ с ФК II-III (ВОЗ) в возрасте 42,5 [37,25; 52,25] года, из них 14 -с впервые установленным диагнозом, ранее не принимавшие специфическую терапию (подгруппа 1), и 10 пациентов, ранее принимавших терапию силденафилом, но не достигших целей лечения (подгруппа 2).…”