Riociguat significantly improves haemodynamics in patients with pulmonary hypertension with HFpEF: DYNAMIC Trial

EUROPE: According to a study published in the European Heart Journal, the vasodilator riociguat enhanced haemodynamics in patients with pulmonary hypertension and heart failure with preserved ejection fraction.

Riociguat was generally considered safe, however it did not alter clinical symptoms during the research period and caused more dropouts than a placebo, according to the authors.

Heart failure (HF) with preserved ejection fraction (HFpEF), which makes up roughly 50% of all instances of HF, is linked to poor quality of life (QoL), significant healthcare resource usage, and early mortality. Clinical heart failure with preserved ejection fraction is significantly made worse by the presence of pulmonary hypertension (PH) (HFpEF). Pulmonary vasodilators have not yet shown any promise as a treatment for heart failure.

In this trial, riociguat, an oral soluble guanylate cyclase activator, was used to treat PH-HFpEF patients over an extended period of time to investigate its efficacy.

For this objective, the PH-HFpEF was evaluated in the phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicenter DYNAMIC study. Five hospitals were chosen to recruit patients in Austria and Germany. Mean pulmonary artery pressure 25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction 50% were important eligibility criteria. Patients were randomly assigned to receive either a placebo or riociguat orally in 1:1 ratio. The dosage was increased for the patients from 0.5 mg TID to 1.5 mg TID. The right heart catheterization-measured change in cardiac output (CO) at rest from baseline to week 26 served as the primary efficacy outcome. On the entire analysis set, primary efficacy analyses were carried out. 56 patients received a placebo, while 58 patients received riociguat.

"The DYNAMIC trial is the first to evaluate the clinical and hemodynamic consequences of long-term administration of the oral sGC stimulator riociguat in PH-HFpEF patients who had not previously received vasoactive therapy," the authors said.

Key conclusive points:

• In the riociguat group, CO surged by 0.37–1.263 L/min after 26 weeks, while it reduced by 0.11–0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval: 0.112–0.971; P = 0.0142).
• Riociguat-related side effects led to the withdrawal of five patients, however no deaths or major side effects from the medication were reported.
• Heart rate (HR) remained constant, with mean changes from baseline in the riociguat group being +1.9 ±  20.8 bpm and -0.9 ±  20.0 bpm in the placebo group.
• With a mean difference between treatments of 0.50 L/min (95% CI: 0.058, 0.937; P = 0.0271), analysis using PPS revealed a comparable result for CO change.
• No appreciable improvements in NT-proBNP serum levels, WHO-FC, exercise capacity, or quality of life were seen in conjunction with the indicated hemodynamic alterations.

The researchers concluded that riociguat was safe in the majority of patients with PH-HFpEF, improved CO, PVR, and further pulmonary haemodynamics, but also caused more dropouts and did not alter clinical symptoms during the study period.

"It is important to do more research in appropriately planned trials to determine whether the use of riociguat may affect clinically significant endpoints of morbidity and death," they added.

REFERENCE

Theresa Marie Dachs, Franz Duca, René Rettl, Christina Binder-Rodriguez, Daniel Dalos, Luciana Camuz Ligios, Andreas Kammerlander, Ekkehard Grünig, Ingrid Pretsch, Regina Steringer-Mascherbauer, Klemens Ablasser, Manfred Wargenau, Julia Mascherbauer, Irene M Lang, Christian Hengstenberg, Roza Badr-Eslam, Johannes Kastner, Diana Bonderman, Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial, European Heart Journal, Volume 43, Issue 36, 21 September 2022, Pages 3402–3413, https://doi.org/10.1093/eurheartj/ehac389