Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension.
BACKGROUND
The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors.


RESULTS
The short-term effects of 8.4 to 10.5 microgram of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4+/-1.3 versus 6.4+/-1.1 mm Hg; P<0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8+/-1.4 versus 9.4+/-1.3 mm Hg; P<0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects.


CONCLUSIONS
Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.
Wilkens
H
H
Medizinische Klinik und Poliklinik, Innere Medizin V, Innere Medizin III, Homburg/Saar, Germany. inhwil@med-rz.uni-saarland.de
Guth
A
A
König
J
J
Forestier
N
N
Cremers
B
B
Hennen
B
B
Böhm
M
M
Sybrecht
G W
GW
D000280:Administration, Inhalation; D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003371:Cough / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D016285:Iloprost