Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study.
BACKGROUND
Phosphodiesterase-5 inhibitors produce a significant decrease in pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension. We studied the effects of tadalafil, a phosphodiesterase-5 inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week period in patients of Eisenmenger syndrome having a pulmonary vascular pathology similar to idiopathic pulmonary arterial hypertension.


RESULTS
Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25+/-8.9 years) were assessed hemodynamically at baseline and 90 minutes after a single dose of tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then continued daily for 12 weeks, and the patients were restudied. There was a significant decrease in mean pulmonary vascular resistance immediately (24.75+/-8.49 to 19.22+/-8.23 Woods units; P<0.005) and at 12 weeks (19.22+/-8.23 to 17.02+/-6.19 Woods units; P=0.03 versus 90 minutes). Thirteen of 16 patients (81.25%) showed a > or = 20% decrease in pulmonary vascular resistance and were defined as responders. The mean systemic oxygen saturation improved significantly both immediately (84.34+/-5.47% to 87.39+/-4.34%; P<0.005) and at 12 weeks (87.39+/-4.34% to 89.16+/-3.8%; P<0.02 versus 90 minutes) without a significant change in systemic vascular resistance. None of the patients had a fall in systemic arterial pressure, worsening of systemic oxygen saturation, or any adverse reactions to the drug. The mean World Health Organization functional class improved from 2.31+/-0.47 to 1.25+/-0.44 (P<0.0001), and the 6-minute walk distance improved from 344.56+/-119.06 to 387.56+/-117.18 m (P<0.001).


CONCLUSIONS
Preliminary evaluation of tadalafil has shown efficacy and safety in selected patients with Eisenmenger syndrome, warranting further investigation in this subgroup of patients.
Mukhopadhyay
Saibal
S
Department of Cardiology, GB Pant Hospital, New Delhi, India 110 002. saibalmukhopadhyay@yahoo.com
Sharma
Manish
M
Ramakrishnan
S
S
Yusuf
Jamal
J
Gupta
Mohit Dayal
MD
Bhamri
Naveen
N
Trehan
Vijay
V
Tyagi
Sanjay
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004541:Eisenmenger Complex / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068581:Tadalafil; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D000068581:Tadalafil; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D010100:Oxygen