Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension
Hossein A. Ghofrani, MD*,
Frank Rose, MD*,
Ralph T. Schermuly, PhD*,
Horst Olschewski, MD*,
Ralph Wiedemann, MD*,
André Kreckel, MD*,
Norbert Weissmann, PhD*,
Stefanie Ghofrani, MD*,
Beate Enke, MD*,
Werner Seeger, MD* and
Friedrich Grimminger, MD, PhD*,*
* Department of Internal Medicine, Pulmonary and Critical Care Medicine, University Hospital, Justus-Liebig-University Giessen, Giessen, Germany.
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Figure 1 Time course of 6-min walk distance in response to iloprost and sildenafil treatment. Mean and SEM are given for the 6-min walk distance. Data were obtained at baseline, after three months of inhaled iloprost therapy (Ilo 3 months), after a mean interval of 18 ± 4 months upon clinical deterioration (Pre-Sil), and after 3, 6, and 9 to 12 months of adjunct sildenafil therapy while leaving the iloprost regimen unchanged (Sil-Ilo). Plus signs with vertical bars on either side demonstrate significant differences in walk distance (assessed by Wilcoxon test, two-sided p values given) for the impact of adjunct sildenafil treatment.
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Figure 2 Distribution of patients (n = 14) in New York Heart Association (NYHA) functional classes. The numbers of patients classified in class II (open bars), III (bars with diagonal lines), or IV (solid bars) are given for the initial pre-intervention baseline, for three months of inhaled iloprost therapy (Ilo 3 months), for a mean interval of 18 ± 4 months when clinical deterioration was noted (Pre-Sil), and for 3, 6, and 9–12 months of adjunct sildenafil therapy while leaving the iloprost regimen unchanged (Sil-Ilo). Note that one patient died between three and six months and one died at eight months of adjunct sildenafil therapy (n = 13 penultimate and n = 12 ultimate column).
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Figure 3 Time course of pulmonary vascular resistance index (PVRI) in response to iloprost and sildenafil treatment. Values for PVRI are presented as the mean and SEM. Open squares represent pre-iloprost values, assessed in the morning after an overnight break of prostanoid inhalation. Closed squares represent PVRI values subsequent to iloprost inhalation. Data pairs (pre- and post-inhalation) were obtained after three months of inhaled iloprost therapy (Ilo 3 months), after a mean interval of 18 ± 4 months on clinical deterioration (Pre-Sil), and after another three months of adjunct sildenafil therapy while leaving the iloprost regimen unchanged (Sil-Ilo). Plus signs with vertical bars on either side demonstrate significant differences (assessed by Wilcoxon test, two-sided p values given) for the impact of adjunct sildenafil treatment.
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