Clinical efficacy, safety, tolerability, and survival outcome of long-term inhaled iloprost treatment in the management of pulmonary arterial hypertension: Data from prospective multicenter observational OPTION study

Abstract

Objective: To evaluate clinical efficacy, safety and tolerability of long-term inhaled iloprost treatment in the daily practice for the management of pulmonary arterial hypertension (PAH). Methods: A total of 115 patients with PAH on inhaled iloprost treatment were included. New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance (6MWD) were recorded at baseline and at 3 rd to 24 th month visits. Safety and tolerability of iloprost treatment were also evaluated during follow-up, as were the survival, clinical worsening, and the related risk factors. Results: The treatment was associated with an increase in the percentage NYHA functional class II (from 0.0% at enrolment to 36.2% at 24 th month visit) patients but no significant difference was noted in 6MWD values. Clinical worsening was observed in 63.5% patients, while survival rate was 69.6%. NT-proBNP levels were significantly higher in non-survivors than in survivors (p=0.042). Cox regression analysis revealed the association of female sex [odds ratio (OR)=0.318; 95% confidence interval (CI), 0.128-0.792; p=0.014] and scleroderma-related PAH (OR=0.347; 95% CI, 0.140-0.860; p=0.022) with significantly lower risk (3.14 fold and 2.88 fold, respectively) of mortality. Conclusion: Our findings indicate favorable efficacy, safety, and tolerability of long-term iloprost treatment in the management of PAH, whereas improved NYHA functional class was not accompanied with a significant change in 6MWD values. Patient age was a risk factor for clinical worsening, while female sex, scleroderma subtype, and lower NT-proBNP levels were associated with significantly lower mortality risk.

Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series

“…Given the retrospective nature and sample size of this report, efficacy of continuous iILO in this complex, dynamic patient population cannot be evaluated. Several adult studies demonstrate efficacy of chronic intermittent iILO for PAH, particularly when administered as add-on and/or combination therapy, 4,7,13,15 with positive primary endpoints of improvement in functional class, 6-min walk test, and cardiopulmonary hemodynamics. In these studies, iILO was delivered 6-9 times daily with reasonable compliance.…”

“…Several adult studies demonstrate efficacy of chronic intermittent iILO for PAH, particularly when administered as add‐on and/or combination therapy, 4,7,13,15 with positive primary endpoints of improvement in functional class, 6‐min walk test, and cardiopulmonary hemodynamics. In these studies, iILO was delivered 6–9 times daily with reasonable compliance 4,7,13,15 . Pediatric studies are limited.…”

“…In these studies, iILO was delivered 6–9 times daily with reasonable compliance. 4 , 7 , 13 , 15 Pediatric studies are limited. Ivy et al 3 report the largest pediatric cohort with 23 patients with Group 1 PAH.…”

“…The elimination half‐life of iloprost is 20–30 min, and pharmacodynamic effects of iILO may be observed up to 30–90 min following a single inhaled dose 1 . Thus, when utilized for sub‐acute or chronic therapy, it requires frequent administration, at least 6–9 times daily 3,7,15 . iILO is typically delivered via the I‐NEB adaptive aerosol delivery (ADD) system, but the effectiveness of iILO with various types of nebulization devices has also been described 7,8,16 .…”

“… 1 Thus, when utilized for sub‐acute or chronic therapy, it requires frequent administration, at least 6–9 times daily. 3 , 7 , 15 iILO is typically delivered via the I‐NEB adaptive aerosol delivery (ADD) system, but the effectiveness of iILO with various types of nebulization devices has also been described. 7 , 8 , 16 The most common side effects associated with iILO administration include cough, headache, flushing, jaw pain, bronchoconstriction, and systemic hypotension.…”