Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study.

Abstract

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.

METHODS AND 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.

• Authors: Saibal Mukhopadhyay, Manish Sharma, S Ramakrishnan, Jamal Yusuf, Mohit Dayal Gupta, Naveen Bhamri, Vijay Trehan, Sanjay Tyagi
• Journal: Circulation (Circulation) Vol. 114 Issue 17 Pg. 1807-10 (Oct 24 2006) ISSN: 1524-4539 [Electronic] United States
• PMID: 17030688 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Carbolines
• Phosphodiesterase Inhibitors
• Vasodilator Agents
• Tadalafil
• 3',5'-Cyclic-GMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 5
• PDE5A protein, human
• Oxygen

Topics

• 3',5'-Cyclic-GMP Phosphodiesterases (antagonists & inhibitors)
• Adult
• Carbolines (administration & dosage, pharmacology, therapeutic use)
• Cyclic Nucleotide Phosphodiesterases, Type 5
• Eisenmenger Complex (blood, drug therapy, enzymology, physiopathology)
• Exercise Tolerance (drug effects)
• Female
• Humans
• Male
• Oxygen (blood)
• Phosphodiesterase Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Tadalafil
• Treatment Outcome
• Vascular Resistance (drug effects)
• Vasodilator Agents (administration & dosage, pharmacology, therapeutic use)