Pulmonary Arterial Hypertension
Scientific Updates – April 2005
Compiled
by
United
Therapeutics Corporation
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J Heart Lung Transplant. 2005 Apr;24(4):501-3. |
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Reversal of pulmonary hypertension and subsequent repair of atrial
septal defect after treatment with continuous intravenous epoprostenol.
Frost AE, Quinones MA, Zoghbi WA, Noon GP.
Baylor College of Medicine, The Methodist Hospital, Houston, Texas, USA.
We report the first case in the world literature of a patient with an atrial
septal defect, severe pulmonary hypertension, and equalization of pulmonary and
systemic pressures, who underwent successful closure of an ASD following
prolonged therapy with the intravenous vasodilator epoprostenol. Judicious use
of continuous prostacyclin in apparently inoperable patients with congenital
heart disease may be associated with significant reversal of pulmonary
hypertension, and conversion to an operable state.
J Heart Lung Transplant. 2005 Apr;24(4):498-500. |
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Novel use of sildenafil in the treatment of portopulmonary hypertension.
Chua R, Keogh A, Miyashita M.
St. Vincent's Hospital, Sydney, New South Wales, Australia.
Portopulmonary hypertension is a poorly understood and uncommon complication of
advanced chronic liver disease. Current therapy is based largely on treatment
options proven in idiopathic pulmonary hypertension. The severity of the
portopulmonary hypertension should best be attenuated medically before attempting
combined liver and lung transplantation to avoid increased peri-operative
mortality. This case report describes the successful use of sildenafil to
decrease the pulmonary vascular resistance in a patient with hepatitis-C
cirrhosis who was preparing for liver transplantation.
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Circ J. 2005 Apr;69(4):461-5. |
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Oral sildenafil improves primary pulmonary hypertension refractory to
epoprostenol.
Kataoka M, Satoh T, Manabe T, Anzai T, Yoshikawa T, Mitamura H, Ogawa S.
Cardiopulmonary
Division, Department of Medicine, Keio University School of Medicine.
Background Epoprostenol (prostaglandin I(2)) has become recognized as a
therapeutic breakthrough that can improve hemodynamics and survival in patients
with primary pulmonary hypertension (PPH). However, a significant number of
patients have PPH that is refractory to epoprostenol, and lung transplantation
has been the only remaining treatment option. Methods and Results The study
subjects included 20 consecutive patients with PPH (mean pulmonary arterial
pressure: 65+/-15 mmHg) who had received epoprostenol for more than 12 months.
The patients were divided into 2 groups; responders and non-responders. In the
non-responders, New York Heart Association (NYHA) functional class did not
improve and mean right atrial pressure (mRA) increased to 8 mmHg or more, and
additional sildenafil, a phosphodiesterase-5 inhibitor, was started. Six
patients were included in the non-responders, whose mRA was 9+/-5 mmHg before
and significantly increased to 13+/-3 mmHg after epoprostenol administration
(p<0.05). One patient died and the other 5 patients received oral
sildenafil. The mRA of 12+/-4 mmHg (value before sildenafil) improved to 8+/-5
mmHg after sildenafil administration. Three patients were classified in the
NYHA functional class 4 and improved to class 3, and 2 patients were in class 3
and remained in the same class after the addition of sildenafil. Conclusions In
patients with severe PPH refractory to epoprostenol treatment, additional oral
sildenafil can improve pulmonary hemodynamics and symptoms. The combination
therapy of epoprostenol and sildenafil is a new medical treatment to attempt
before progressing to lung transplantation for patients with PPH refractory to
epoprostenol. (Circ J 2005; 69: 461 - 465).
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Ann Pharmacother. 2005 May;39(5):869-84. Epub 2005 Apr 12. |
Sildenafil for pulmonary hypertension.
Lee AJ, Chiao TB, Tsang MP.
Thomas J Long School of Pharmacy, University of the Pacific; Clinical
Specialist, Internal Medicine, Veterans Affairs Medical Center, San Francisco,
CA.
OBJECTIVE: To evaluate the efficacy of sildenafil for treatment of pulmonary
hypertension. DATA SOURCES: Literature retrieval was accessed through MEDLINE
(1977-March 2005), Cochrane Library, and International Pharmaceutical Abstracts
(1977-March 2005) using the terms sildenafil and pulmonary hypertension. In
addition, reference citations from publications identified were reviewed. STUDY
SELECTION AND DATA EXTRACTION: All articles in English identified from the data
sources were evaluated. Studies including >5 patients with primarily adult
populations were included in the review. DATA SYNTHESIS: The treatment of
pulmonary hypertension is challenging. Sildenafil has recently been studied as
monotherapy and in combination with other vasodilators in the management of
pulmonary hypertension. Eight hemodynamic studies and 12 clinical trials were
reviewed (1 retrospective, 3 double-blind, 8 open-label). Sildenafil reduced
pulmonary arterial hypertension and pulmonary vascular resistance/peripheral
vascular resistance index and tended to increase cardiac output/cardiac index
compared with baseline. Sildenafil was comparable to nitric oxide and at least
as effective as iloprost or epoprostenol in terms of its pulmonary
vasoreactivity. Combination therapy with iloprost, nitric oxide, or
epoprostenol resulted in enhanced and prolonged pulmonary vascular effects.
Clinical trials suggest that sildenafil improves exercise tolerance and New
York Heart Association functional class, but large, randomized controlled
trials are needed to confirm these findings. Overall, sildenafil was well
tolerated. CONCLUSIONS: Overall, sildenafil is a promising and well-tolerated
agent for management of pulmonary hypertension. Further well-designed trials
are warranted to establish its place in the treatment of pulmonary
hypertension.
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Int J Cardiol. 2005 Apr 20;100(2):267-73. |
Safety and efficacy of Sildenafil therapy in children with pulmonary
hypertension.
Karatza AA, Bush A, Magee AG.
Department of Paediatric Cardiology, Royal Brompton Hospital, Sydney Street,
SW3 6NP, London, UK.
OBJECTIVE: Sildenafil is a selective Phosphodiesterase-5 inhibitor that has
been reported to be a potent pulmonary vasodilator. We evaluated the safety,
efficacy and pharmacokinetics of oral Sildenafil in a case series of children
with pulmonary hypertension. METHODS: Three children, 1 with primary pulmonary
hypertension (patient 1) and 2 with pulmonary hypertension associated with
congenital heart disease (patients 2 and 3) were enrolled. Sildenafil was
started at 0.5 mg/kg 4-hourly and the dose increased to 1.0 and then to 2.0
mg/kg/dose. Patients were assessed at baseline and then monthly for a total of
6 visits. RESULTS: All patients reported increased exercise capacity with
improvement in New York Heart Association functional class. The distance walked
during the 6-min test increased by 74% (patient 1), 75% (patient 2) and 25%
(patient 3) and oxyhaemoglobin saturations increased from 79%, 97% and 80% to
93%, 100% and 93%, respectively. There were no side effects and no fall in
systemic blood pressure. Sildenafil plasma levels 1 h after a 0.5, 1.0 and 2
mg/kg dose of Sildenafil were 109+/-87, 150+/-62 and 368+/-200 ng/ml,
respectively. They fell to 211+/-106 ng/ml 3 h after the 2.0 mg/kg dose.
CONCLUSIONS: Medium term Sildenafil therapy improves oxyhaemoglobin saturations
and exercise tolerance in children with pulmonary hypertension without any side
effects. Mean plasma levels 1 h after doses of 0.5-2.0 mg/kg are similar to the
maximum plasma concentrations reported in adults receiving doses within the
therapeutic range. Sildenafil use in children appears to be safe and may be
beneficial in the management of pulmonary arterial hypertension.