PRS7 Efficacy and Safety of Sildenafil Above 60 mg Daily in Pulmonary Arterial Hypertension Treatment - a Systematic Literature Review

Abstract

To assess efficacy and safety of dornase alfa in the treatment of cystic fibrosis (CF) in children and adults. METHODS: Systematic review of Medline, Em-Base, CENTRAL and clinicaltrials.gov databases was conducted. The references from relevant articles and abstracts from conferences were also examined to identify any additional studies. Each full-text article was critically appraised with use of the Jadad Scale. Clinical practice and CF treatment procedures in Poland were consulted with clinical experts. Placebo and treatment without dornase were identified as potential comparators. Changes in FEV 1 , FVC, and FEF 25%-75% , exacerbation of respiratory symptoms, body mass change, use of drugs, number of days spent at home due to CF, hospitalizations (number and length), ambulatory visits, quality of life, mortality rate, treatment acceptance by patient and safety were assessed and compared based on the review results. RESULTS: Among 294 reports found, 17 publications concerning 12 randomized clinical trials were included in the analysis. The meta-analysis of available data regarding changes in FEV 1 after 1, 3, 6 months and 1 and 2 years showed better results with dornase therapy. The use of dornase also improved pulmonary function measured in FVC. Exacerbations of respiratory symptoms were less frequent (by 20% when dornase alpha was administered once daily and by 34% when administered twice daily), which resulted in fewer hospitalizations. Patients treated with dornase required less frequent courses of intravenous antibiotics and spent fewer days at home due to CF. Safety analysis showed a higher risk of rash, voice alteration and pharyngitis with dornase. Mortality was similar among groups. CONCLUSIONS: Dornase alfa is an effective (improves respiratory function, reduces CF symptoms, dyspnea and respiratory system exacerbations) and safe therapeutic option.

Sildenafil for Asian Adult Patients with Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

“…In this study, we focused on 20 mg/TID, and included participants who were mainly idiopathic PAH, as well as CTD and CHD related PAH. The results on 6MWD, mean PAP, dyspnoea score, level of BNP were similar to those identi ed in other systematic reviews [16,[21][22][39][40][41][42] . As an important indicator for severity evaluation and prognosis [43] , previous studies have shown that there was a signi cant improvement in WHO functional class favouring sildena l when comparing to placebo [16] .…”

Sildenafil for adult Asian patients with pulmonary arterial hypertension: a systematic review and meta-analysis

“…In this study, we focused on 20 mg/TID, and included participants who were mainly idiopathic PAH, as well as CTD and CHD-related PAH. The results of 6MWD, mean PAP, dyspnoea score, and level of BNP were similar to those identified in other systematic reviews (16,21,22,(43)(44)(45)(46). As an important indicator for severity evaluation and prognosis (47), previous studies have shown that there is a significant improvement in WHO functional class favouring sildenafil comparing to the placebo (16).…”

“…Among these, both the FDA and EMA recommended that sildenafil be orally administered at a dose of 20 mg/TID. Although increasing evidence has suggested that sildenafil therapy is beneficial (21,22,(43)(44)(45)(46), the dose varies greatly. A Cochrane systematic review published in 2019 indicated that sildenafil has a better therapeutic effect, with a lower incidence of adverse events compared to the placebo (16).…”