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Long-term Survival of Patients with Pulmonary Hypertension Treated with Different Iloprost and Sildenafil Combination Regimens

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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Henning Gall

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Combination therapies for pulmonary hypertension (PH) are often used in patients who do not respond adequately to monotherapy; however, specific treatment guidelines on this topic are lacking and there is a need for more data on the relative efficacies of particular PH therapy combinations.

Background: Combination therapies for pulmonary hypertension (PH) are often used in patients who do not respond adequately to monotherapy; however, specific treatment guidelines on this topic are lacking and there is a need for more data on the relative efficacies of particular PH therapy combinations. This study aimed to examine long-term effects of different combination regimens of inhaled iloprost and oral sildenafil on survival and disease progression in patients with PH.

Methods: This was an observational, retrospective study of adults registered in the Giessen Pulmonary Hypertension Registry who were receiving inhaled iloprost with oral sildenafil. Three treatment regimens were studied: initial iloprost monotherapy with subsequent addition of sildenafil (ilo/sil); initial sildenafil monotherapy followed by addition of iloprost (sil/ilo); and upfront combination therapy of iloprost and sildenafil (ilo+sil). The primary outcome was survival, calculated by Kaplan–Meier analysis. When available, 6-minute walk distance (6MWD), pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and cardiac output data were obtained before treatment (pre-treatment baseline), 3 months after monotherapy initiation, before combination therapy (post-monotherapy baseline) and 3 months after starting combination therapy. Changes were compared by intra-individual analysis.

Results: A total of 148 patients were included in the study (ilo/sil, n=61; sil/ilo, n=63; ilo+sil, n=24). At pre-treatment baseline, patients receiving upfront combination therapy had significantly higher mean PAP and PVR than patients treated initially with monotherapy (p<0.001); however, there was no significant difference in cardiac output among regimens (p=0.264). All-cause mortality differed significantly among treatment groups (p=0.007; log-rank test). Cumulative survival was highest in patients receiving iloprost first (1-year survival rates: ilo/sil, 95.1%; sil/ilo, 91.8%; ilo+sil, 62.9%); this group also remained on monotherapy significantly longer than the group treated initially with sildenafil (p=0.004). With both add-on combinations, mean 6MWD increased significantly compared with pre-treatment baseline (ilo/sil, from 283 to 374 m, p < 0.001; sil/ilo, from 280 to 312 m, p = 0.038), and with post-monotherapy baseline (ilo/sil, from 345 to 374 m, p = 0.01; sil/ilo, from 303 to 328 m, p = 0.002). A significant improvement from the mean pre-treatment 6MWD was also seen in patients receiving the upfront combination regimen for 3 months (from 213 to 305 m; p=0.001). Following addition of sildenafil, hemodynamic variables improved significantly when compared with post-monotherapy baseline levels (mean PAP, p=0.037; mean cardiac output, p=0.001; mean PVR, p=0.006), but only mean PVR improved significantly relative to pre-treatment levels (p=0.006). In patients receiving upfront combination therapy, mean PAP decreased significantly after 3 months when compared with pre-treatment values (p=0.018).

Conclusions: The sequence in which patients with PH received combination therapy with iloprost and sildenafil was independently associated with survival rates: cumulative survival was highest in patients who received iloprost first. However, owing to the size and retrospective design of this study, further research on this topic is needed before a firm treatment recommendation can be made. 

Type: Clinical Science