title: Survival with sildenafil and inhaled iloprost in a cohort with pulmonary hypertension: an observational study.
abstract: BACKGROUND
  Combination therapy is frequently used to treat patients with pulmonary hypertension but few studies have compared treatment regimens. This study examined the long-term effect of different combination regimens of inhaled iloprost and oral sildenafil on survival and disease progression.
  
  
  METHODS
  This was a retrospective study of patients in the Giessen Pulmonary Hypertension Registry who received iloprost monotherapy followed by addition of sildenafil (iloprost/sildenafil), sildenafil monotherapy followed by addition of iloprost (sildenafil/iloprost), or upfront combination therapy (iloprost + sildenafil). The primary outcome was transplant-free survival (Kaplan-Meier analysis). When available, haemodynamic parameters and 6-minute-walk distance were evaluated.
  
  
  RESULTS
  Overall, 148 patients were included. Baseline characteristics were similar across treatment groups; however, the iloprost + sildenafil cohort had higher mean pulmonary vascular resistance and pulmonary arterial pressure than the others. Transplant-free survival differed significantly between groups (P = 0.007, log-rank test). Cumulative transplant-free survival was highest for patients who received iloprost/sildenafil (1 year survival: iloprost/sildenafil, 95.1%; sildenafil/iloprost, 91.8%; iloprost + sildenafil, 62.9%); this group also remained on monotherapy significantly longer than the sildenafil/iloprost group (median 17.0 months vs 7.0 months, respectively; P = 0.004). Compared with pre-treatment values, mean 6-minute-walk distance increased significantly for all groups 3 months after beginning combination therapy.
  
  
  CONCLUSIONS
  In this observational study of patients with pulmonary hypertension receiving combination therapy with iloprost and sildenafil, cumulative transplant-free survival was highest in those who received iloprost monotherapy initially. However, owing to the size and retrospective design of this study, further research is needed before making firm treatment recommendations.
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. henning.gall@innere.med.uni-giessen.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Gall
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Natascha.Sommer@innere.med.uni-giessen.de.
authors.forename: Natascha
authors.initials: N
authors.lastname: Sommer
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. katrin.milger@gmail.com.|Medical Clinic V, University of Munich, Comprehensive Pneumology Center, Munich, Germany. katrin.milger@gmail.com.
authors.forename: Katrin
authors.initials: K
authors.lastname: Milger
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Manuel.J.Richter@t-online.de.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Richter
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. rvoswin@me.com.|Department of Internal Medicine, Friedberg Hospital, Friedberg, Germany. rvoswin@me.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Dirk.Bandorski@hkw.med.uni-giessen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bandorski
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Werner.Seeger@innere.med.uni-giessen.de.|Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. Werner.Seeger@innere.med.uni-giessen.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Friedrich.Grimminger@innere.med.uni-giessen.de.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Universities of Giessen & Marburg Lung Center, Medizinische Klinik II, Klinikstraße 33, 35392, Giessen, Germany. Ardeschir.Ghofrani@innere.med.uni-giessen.de.|Faculty of Medicine, Imperial College London, London, UK. Ardeschir.Ghofrani@innere.med.uni-giessen.de.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D016285:Iloprost / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D015996:Survival Rate; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D016285:Iloprost