Transition from phosphodiesterase-5 inhibitors (PDE5i) — such as United Therapeutics’ Adcirca (taladafil) and Pfizer‘s Revatio (sildenafil) — to Bayer‘s Adempas (riociguat), a soluble guanylate cyclase (sGC) stimulator, without a washout period is a viable option for some patients with pulmonary hypertension, a small study suggests.
The study, “Successful Transition from Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study,” was published in the journal Heart, Lung and Circulation.
Pulmonary arterial hypertension (PAH) is a rare, life-threatening disorder caused by a narrowing of the arteries in the lungs, leading to high blood pressure. Over the last decade, therapies have substantially improved, with the generation of PAH-specific drugs with different mechanisms of action that can be combined to provide the best possible outcome for each patient.
PDE5i and sGCs are both vasodilator compounds — agents that induce blood vessels’ widening and relaxation. They do so in different ways, but cannot be used as a therapeutic combination.
“Because sGC stimulator cannot be co-administered with a PDE5i because of the risk of systemic [low blood pressure], drug transition is considered in patients with an intolerance or inadequate clinical response to PDE5i,” the researchers stated.
Patients who transition from one medication to another, immediately or with a short washout period, may develop hemodynamic instability — a medical condition in which the body’s circulatory system fails to maintain a constant blood circulation because of lack of blood pressure.
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“A previous study [RESPITE trial, NCT02007629] suggested that selected patients with PAH may benefit from switching from PDE5i to sGC stimulator with a washout period. However, the feasibility of transitioning from a PDE5i to an sGC stimulator and the washout period required for transition have not been clearly established,” the researchers said.
Therefore, a team of Japanese investigators set out to test whether transitioning from Adcirca and Revatio (PDE5i) to Adempas (an sGC stimulator) would be safe without a washout period in patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH).
The pilot cohort study enrolled six patients with PAH and one with CTEPH, who had already received dual- or triple-combination therapy. All patients were monitored for signs of hemodynamic instability by heart catheterization, a procedure in which a thin catheter is inserted into blood vessels and threaded into the heart to diagnose and treat heart problems.
Three patients switched from PDE5i treatment to Adempas because of side effects (severe headaches) associated with PDE5i treatment; four switched because of inadequate therapy response.
Results showed that all patients transitioned successfully without a washout period, with no signs of hemodynamic instability.
Immediately after the transition, pulmonary vascular resistance (PVR, a measure of heart strain induced by high blood pressure in the lungs) dropped (from 797 to 518 dyne/s/cm–5), as well as systemic blood pressure (a significant drop from 121 to 100 mmHg) in all patients.
The most common side effects associated with PDE5i disappeared after transition to Adempas.
“Transition from a PDE5i to [Adempas] without washout periods is safe. This transition may be a viable option for patients with PAH and side effects, such as headache, caused by PDE5i or who experience an inadequate response to combination therapy including PDE5i,” the team concluded.
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