CHEST Guidelines-Acute-Hemodynamic-Effects-of-Riociguat-in-Patients

Acute-Hemodynamic-Effects-of-Riociguat-in-Patients

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The study "Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1)" evaluates the impact of riociguat, a soluble guanylate cyclase stimulator, on patients with pulmonary hypertension (PH) linked to heart failure with preserved ejection fraction (HFpEF). This randomized, double-blind, placebo-controlled trial aimed to assess the acute effects of single oral doses of riociguat (0.5 mg, 1 mg, or 2 mg) compared to a placebo.<br /><br />Results indicated that riociguat did not significantly change the primary efficacy measure, mean pulmonary artery pressure (mPAP), within six hours post-administration. However, the 2 mg dose of riociguat increased stroke volume and cardiac index, decreased systolic blood pressure and systemic vascular resistance, and significantly reduced the right ventricular end-diastolic area without altering heart rate, pulmonary arterial wedge pressure, transpulmonary pressure gradient, or pulmonary vascular resistance. These changes suggest an improvement in exploratory hemodynamic and echocardiographic parameters while riociguat was well tolerated among patients.<br /><br />Riociguat's mode of action includes sensitizing soluble guanylate cyclase to nitric oxide, leading to vasodilation. This study reflects its potential to enhance cardiac output and manage pulmonary hypertension without worsening left-sided heart pressures. Although the study's sample size was limited, and baseline differences existed, resulting favorable outcomes support exploring riociguat in chronic, large-scale studies possibly for long-term treatment benefits in HFpEF patients with PH.<br /><br />Therefore, while mPAP was unchanged, the positive shifts in other cardiac markers suggest that riociguat could aid heart function and highlight the necessity of continuous research in sGC stimulators for heart failure therapy. Potential therapeutic benefits warrant further investigation, alongside comprehensive safety assessments and longer-term evaluations.

Keywords

Riociguat

Pulmonary Hypertension

Diastolic Heart Failure

HFpEF

Hemodynamic Effects

Cardiac Output

Vasodilation

sGC Stimulators

Echocardiographic Parameters

Heart Failure Therapy