One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

Abstract

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Granulomatous angiitis leading to a pulmonary veno-occlusive disease-like picture

“…Bosentan was poorly tolerated by the patient, inducing probable pulmonary oedema. Sildenafil has been tolerated in PVOD in two previous case reports [15,16].…”

Pulmonary veno-occlusive disease: advances in clinical management and treatments

“…However, none of these patients developed pulmonary edema during acute testing with NO, nor were any of the clinical, functional or hemodynamic characteristics predictive of the onset of this complication after initiation of specific PAH therapy [8]. In selected cases, there have been reported mild clinical improvement or stabilization with continuous intravenous epoprostenol [10, [80][81][82][83], iloprost therapy [84,85] and oral sildenafil [86,87]. In contrast with idiopathic PAH, the benefits of specific PAH treatments in patients with PVOD remain unclear.…”

Seguimento de dois anos em pacientes com hipertensão arterial pulmonar sob tratamento com sildenafila

“…Así, con excepción del epoprostenol (derivado de la prostaciclina para uso por vía intravenosa), utilizado ya por más de dos décadas, los efectos a largo plazo de las así llamadas "nuevas drogas" apenas comienzan a ser conocidos. En nuestra institución, tuvimos la oportunidad de verificar los efectos del sildenafil en portadores de HAP idiopática o asociada a cardiopatías congénitas, en un estudio abierto de 12 meses de duración 11 . Debe destacarse, sin embargo, que a la luz de los conocimientos actuales, es poco probable que un grupo de pacientes con HAP se mantenga estable por largo tiempo bajo tratamiento con monodroga, pese a que esto sea posible en situaciones particulares.…”