Lower doses of bosentan in combination with sildenafil might be beneficial in pulmonary arterial hypertension

Abstract

Background:Endothelin-receptor-antagonist, bosentan, has been found to improve the functional capacity and cardiopulmonary hemodynamics in Pulmonary Arterial Hypertension (PAH). Clinical trials have shown the preferable dosage of 125 mg, twice daily, regarding both efficacy and safety.Objectives:The purpose of this study was to investigate the effects of lower doses of bosentan (62.5 mg, twice daily) in combination with sildenafil on exercise capacity and clinical events, in 41 patients with idiopathic pulmonary hypertension or chronic thromboembolic pulmonary hypertension (CTEPH).Patients and Methods:We assigned 41 patients with PAH (non-reactive idiopathic or non-operable chronic thromboembolic) to receive 62.5 mg of bosentan twice daily as combination therapy and evaluated the New York heart association (NYHA) functional class, 6-minutes-walk-distance (6MWD), time to clinical worsening, echocardiographic indexes and clinical events, for an average of 18.5 ± 9.5 months.Results:No adverse drug reaction was observed during the follow-up. Clinical worsening occurred in six (14%) patients, at least one year after treatment, two of the cases failed to respond to 125 mg, twice daily and died. Eight (19%) remained in FC I_II, but didn’t reach the goal of 380 meters for 6MWD. All other patients reached the treatment goals according to the latest European society of cardiology (ESC) guidelines.Conclusions:We observed acceptable results regarding both efficacy and safety with 62.5 mg of bosentan, twice daily in this group of patients. Further clinical trials investigating PAH with lower dosages of bosentan may be warranted.

Transition from Ambrisentan to Bosentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study

“…Due to these reasons, we measured the WHO FC as another effective functional index. FC is an important end point tool [ 14 ], as a supplement to the exercise capacity. In these patients, WHO FC was unchanged ( N = 5/2/1 and 11/1/0, resp.).…”

Organbadversuche an humanen Pulmonalgefäßen: Beurteilung der Medikamentenwirkung zur Behandlung der pulmonalarteriellen Hypertonie

“…In einer nicht placebokontrollierten Studie an 41 Patienten hatten sich bspw. bereits Hinweise auf eine adäquate Wirkung niedrigerer Bosentandosierungen in Kombination mit Sildenafil ergeben [25]. In weiteren Studien waren neben einer signifikanten Besserung hämodynamischer Parameter wie Herzindex (HI), pulmonalvaskulärem Widerstand (PVR) oder dem pulmonalarteriellen Mitteldruck (mPAP) im Regelfall auch deutliche Verbesserungen der Symptomatik zu verzeichnen, was sich in einem relevanten Anstieg der 6-Minuten-Gehstrecke (6MWD) oder einer Verbesserung der WHO-Funktionsklasse (WHO-FC) objektivieren ließ [26 -28].…”