Faculty Opinions recommendation of Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.
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Read the full review for this Faculty Opinions recommended article: Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.Keywords:
On demand
Open label
Background: Phosphodiesterase type-5 inhibitors (iPDE5) are one of the mainstays of Pulmonary Arterial Hypertension (PAH) treatment. Tadalafil is an alternative to sildenafil with the advantage of a less frequent dosing (once instead of 3-times daily). Aim: To examine the feasibility of transitioning PAH patients from sildenafil to taladafil. Methods: We studied twenty clinically stable PAH outpatients from a single pulmonary vascular disease centre receiving sildenafil that were transitioned to tadalafil. We compared validated biochemical and functional capacity measures from the last visit under sildenafil and last follow-up visit under taladafil. Results: Patients had a mean age of 48±18 years and 75% were female. No significant differences were found between the sildenafil and taladafil evaluations. The proportion of patients at NYHA functional class 1 or 2 (65% vs 60%; p=0.16) was similar, as was the Borg class (0.5±1.1 vs 0.5±1.0; p=1.00) and 6-minute walking distance (393±168 vs 368±199 m; p=0.31). Similarly, NT-pro-BNP was stable between evaluations (590 [247-1929] vs 496 [310-2393] ng/mL; p=0.32). The median time between evaluations was 6 [4-7] months. One patient reported lower limb myalgia and had to suspend tadalafil. No other significant adverse effects were reported. Conclusions: Transitioning from sildenafil to taladafil was feasible as it was not associated with clinical worsening of PAH patients. Tadalafil was well tolerated in all patients but one, who developed myalgia that prevented treatment continuation.
myalgia
Group B
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Vardenafil
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Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model. Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens. Contractile forces were determined in an organ bath. Vessels were constricted with norepinephrine (NE) to determine the effects of sildenafil, tadalafil and vardenafil and with ET-1 to assess the effects of bosentan. All 3 PDE-5 inhibitors had no relevant effect on the basal tone of the vessels. Both sildenafil and vardenafil significantly (P < 0.0001) reduced the responses of the vessels to NE, whereas tadalafil was effective only in PA (P = 0.0009) but not in PV (P = 0.097). Sildenafil relaxed NE-preconstricted PV (P < 0.0001) but not PA (P = 0.143). Both tadalafil and vardenafil relaxed PA and PV significantly. Vardenafil appears to be the most potent of the PDE-5 inhibitors tested. Furthermore, we analysed the combination of bosentan and vardenafil in PA. Bosentan and vardenafil reduced ET-1 and NE induced vasoconstriction stronger than vardenafil alone (P ≤ 0.049). Vardenafil caused the most consistent antihypertensive response in this ex vivo model. However, ET receptor antagonism appears to be an even more potent mechanism. A combination therapy using vardenafil and bosentan turned out to be an effective combination to lower vessel tension in PA.
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Oxygen Saturation
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Introduction: Sildenafil (Revatio®) and tadalafil (Adcirca®) are specific inhibitors of the phosphodiesterase-5 enzyme and produce pulmonary vasodilation by inhibiting the breakdown of cyclic guanosine monophosphate (cGMP) in the walls of pulmonary arterioles.Areas covered: We focus on the efficacy and safety of sildenafil and tadalafil in the treatment of pulmonary hypertension (PH) in children through a PubMed literature search.Expert opinion: Although used since 1999 in the treatment of PH in children, it is only in the past few years that robust evidence for the use of sildenafil has emerged principally in the pivotal STARTS-1 study. The open-label extension of this study, STARTS-2, has revealed safety concerns substantiated by FDA post marketing surveillance leading to recommendations to use lower doses. More recently, tadalafil has been introduced allowing once daily dosing with apparently similar efficacy to sildenafil in children. Recently there have been suggestions that sildenafil and tadalafil may have a place in treating muscular dystrophy.
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