CLINICAL STUDIES
Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension
Noritoshi Nagaya, MD*,
Masaaki Uematsu, MD, PhD ,
Yoshiaki Okano, MD ,
Toru Satoh, MD, PhD*,
Shingo Kyotani, MD, PhD*,
Fumio Sakamaki, MD, PhD*,
Norifumi Nakanishi, MD, PhD*,
Kunio Miyatake, MD, PhD, FACC* and
Takeyoshi Kunieda, MD, PhD
* Division of Cardiology, Department of Medicine, National Cardiovascular Center, Osaka, Japan
Cardiovascular Division, Osaka Police Hospital, Osaka, Japan
Department of Clinical Laboratory Medicine, Kyoto University Hospital, Kyoto, Japan
Department of Medicine, Ise Keio Hospital, Keio University, Mie, Japan
Manuscript received May 28, 1998;
revised manuscript received May 4, 1999,
accepted June 11, 1999.
Reprint requests and correspondence: Noritoshi Nagaya, MD, Division of Cardiology, Department of Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565, Japan
OBJECTIVES
This study sought to investigate the effect of beraprost sodium (BPS), an orally active prostacyclin analogue, on the survival of outpatients with primary pulmonary hypertension (PPH).
BACKGROUND
Continuous intravenous administration of epoprostenol (prostacyclin) has been shown to improve survival in PPH. However, the effect of oral BPS on survival in PPH remains unknown.
METHODS
Fifty-eight consecutive patients with PPH who could be discharged after the first diagnostic catheterization for PPH were retrospectively divided into two groups: patients treated with BPS (BPS group, n = 24) and those without BPS (conventional group, n = 34). The baseline demographic and hemodynamic data did not significantly differ between the two.
RESULTS
Twenty-seven patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 44 ± 45 months. In contrast, only 4 patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 30 ± 20 months. In a subsample (n = 15) of patients in the BPS group, mean pulmonary arterial pressure and total pulmonary resistance significantly decreased, respectively, by 13% and 25% during a mean follow-up period of 53 days. Among the variables previously known to be associated with the mortality in PPH, the absence of BPS therapy and the reduced cardiac output were independently related to the mortality by a multivariate Cox proportional hazards regression analysis (both p < 0.05). The Kaplan-Meier survival curves demonstrated that the one-, two- and three-year survival rates for the BPS group were 96%, 86% and 76%, respectively, as compared with 77%, 47% and 44%, respectively, in the conventional group (log-rank test, p < 0.05).
CONCLUSIONS
The oral administration of BPS may have beneficial effects on the survival of outpatients with PPH as compared with conventional therapy alone.
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Abbreviations and Acronyms
| | BPS | = beraprost sodium | | PPH | = primary pulmonary hypertension |
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281(48):
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|
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172(12):
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December 1, 2005;
60(12):
981 - 983.
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December 1, 2005;
128(6_suppl):
622S - 628S.
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|
S. Provencher, X. Jais, A. Yaici, O. Sitbon, M. Humbert, and G. Simonneau
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December 1, 2005;
128(6_suppl):
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|
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|
|
|
|
|
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May 1, 2005;
127(5):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Badesch, S. H. Abman, G. S. Ahearn, R. J. Barst, D. C. McCrory, G. Simonneau, and V. V. McLaughlin
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July 1, 2004;
126(1_suppl):
35S - 62S.
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|
|
|
|
|
|
|
V. V. McLaughlin, K. W. Presberg, R. L. Doyle, S. H. Abman, D. C. McCrory, T. Fortin, and G. Ahearn
Prognosis of Pulmonary Arterial Hypertension*: ACCP Evidence-Based Clinical Practice Guidelines
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July 1, 2004;
126(1_suppl):
78S - 92S.
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|
|
|
|
|
|
|
E. Berman Rosenzweig, K. A. Schmitt, R. Garofano, and R. J. Barst
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March 1, 2004;
125(3):
1157 - 1160.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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109(3):
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[Full Text]
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|
|
|
|
|
|
|
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January 1, 2004;
169(1):
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[Full Text]
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|
|
|
|
|
|
|
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Effects of the Dual Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Arterial Hypertension: A 1-Year Follow-up Study
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July 1, 2003;
124(1):
247 - 254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Barst, M. McGoon, V. McLaughlin, V. Tapson, R. Oudiz, S. Shapiro, I. M. Robbins, R. Channick, D. Badesch, B. K. Rayburn, et al.
Beraprost therapy for pulmonary arterial hypertension
J. Am. Coll. Cardiol.,
June 18, 2003;
41(12):
2119 - 2125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ono, N. Nagaya, H. Okumura, Y. Shimizu, S. Kyotani, N. Nakanishi, and K. Miyatake
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May 1, 2003;
123(5):
1583 - 1588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Budhiraja and P. M. Hassoun
Portopulmonary Hypertension: A Tale of Two Circulations
Chest,
February 1, 2003;
123(2):
562 - 576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Stitham, A. Stojanovic, B. L. Merenick, K. A. O'Hara, and J. Hwa
The Unique Ligand-binding Pocket for the Human Prostacyclin Receptor. SITE-DIRECTED MUTAGENESIS AND MOLECULAR MODELING
J. Biol. Chem.,
January 31, 2003;
278(6):
4250 - 4257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Widlitz and R.J. Barst
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Eur. Respir. J.,
January 1, 2003;
21(1):
155 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Galie, A. Manes, and A. Branzi
The new clinical trials on pharmacological treatment in pulmonary arterial hypertension
Eur. Respir. J.,
October 1, 2002;
20(4):
1037 - 1049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chatterjee, T. De Marco, and J. S. Alpert
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Arch Intern Med,
September 23, 2002;
162(17):
1925 - 1933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Stitham, A. Stojanovic, and J. Hwa
Impaired Receptor Binding and Activation Associated with a Human Prostacyclin Receptor Polymorphism
J. Biol. Chem.,
May 3, 2002;
277(18):
15439 - 15444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Galie, M. Humbert, J.-L. Vachiery, C. Vizza, M. Kneussl, A. Manes, O. Sitbon, A. Torbicki, M. Delcroix, R. Naeije, et al.
Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial
J. Am. Coll. Cardiol.,
May 1, 2002;
39(9):
1496 - 1502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Hoeper, N. Galie, G. Simonneau, and L. J. Rubin
New Treatments for Pulmonary Arterial Hypertension
Am. J. Respir. Crit. Care Med.,
May 1, 2002;
165(9):
1209 - 1216.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Nagaya, Y Shimizu, T Satoh, H Oya, M Uematsu, S Kyotani, F Sakamaki, N Sato, N Nakanishi, and K Miyatake
Oral beraprost sodium improves exercise capacity and ventilatory efficiency in patients with primary or thromboembolic pulmonary hypertension
Heart,
April 1, 2002;
87(4):
340 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. SIMONNEAU, R. J. BARST, N. GALIE, R. NAEIJE, S. RICH, R. C. BOURGE, A. KEOGH, R. OUDIZ, A. FROST, S. D. BLACKBURN, et al.
Continuous Subcutaneous Infusion of Treprostinil, a Prostacyclin Analogue, in Patients with Pulmonary Arterial Hypertension . A Double-blind, Randomized, Placebo-controlled Trial
Am. J. Respir. Crit. Care Med.,
March 15, 2002;
165(6):
800 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.M. Hoeper
Pulmonary hypertension in collagen vascular disease
Eur. Respir. J.,
March 1, 2002;
19(3):
571 - 576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Clapp, P. Finney, S. Turcato, S. Tran, L. J. Rubin, and A. Tinker
Differential Effects of Stable Prostacyclin Analogs on Smooth Muscle Proliferation and Cyclic AMP Generation in Human Pulmonary Artery
Am. J. Respir. Cell Mol. Biol.,
February 1, 2002;
26(2):
194 - 201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R WILKINS and J. WHARTON
Progress in, and future prospects for, the treatment of primary pulmonary hypertension
Heart,
December 1, 2001;
86(6):
603 - 604.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C D Vizza, S Sciomer, S Morelli, C Lavalle, P Di Marzio, D Padovani, R Badagliacca, A R Vestri, R Naeije, and F Fedele
Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue
Heart,
December 1, 2001;
86(6):
661 - 665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W Budts, N Van Pelt, H Gillyns, M Gewillig, F Van de Werf, and S Janssens
Residual pulmonary vasoreactivity to inhaled nitric oxide in patients with severe obstructive pulmonary hypertension and Eisenmenger syndrome
Heart,
November 1, 2001;
86(5):
553 - 558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Galiè and A. Torbicki
GENERAL CARDIOLOGY: Pulmonary arterial hypertension: new ideas and perspectives
Heart,
April 1, 2001;
85(4):
475 - 480.
[Full Text]
|
|
|
|
|
|
|
N. NAGAYA, M. UEMATSU, H. OYA, N. SATO, F. SAKAMAKI, S. KYOTANI, K. UENO, N. NAKANISHI, M. YAMAGISHI, and K. MIYATAKE
Short-term Oral Administration of L-Arginine Improves Hemodynamics and Exercise Capacity in Patients with Precapillary Pulmonary Hypertension
Am. J. Respir. Crit. Care Med.,
March 15, 2001;
163(4):
887 - 891.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. L BAILEY, R. N CHANNICK, and L. J RUBIN
A new era in the treatment of primary pulmonary hypertension
Heart,
March 1, 2001;
85(3):
251 - 252.
[Full Text]
|
|
|
|
|
|
|
N. Galie
Do we need controlled clinical trials in pulmonary arterial hypertension?
Eur. Respir. J.,
January 1, 2001;
17(1):
1 - 3.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Higenbottam and T. Siddons
Trials of inhaled Iloprost and other new vasodilating prostaglandins
Eur. Respir. J.,
January 1, 2001;
17(1):
6 - 7.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Nagaya, T Nishikimi, M Uematsu, T Satoh, H Oya, S Kyotani, F Sakamaki, K Ueno, N Nakanishi, K Miyatake, et al.
Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension
Heart,
December 1, 2000;
84(6):
653 - 658.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Archer and S. Rich
Primary Pulmonary Hypertension : A Vascular Biology and Translational Research "Work in Progress"
Circulation,
November 28, 2000;
102(22):
2781 - 2791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nagaya, T. Nishikimi, M. Uematsu, T. Satoh, S. Kyotani, F. Sakamaki, M. Kakishita, K. Fukushima, Y. Okano, N. Nakanishi, et al.
Plasma Brain Natriuretic Peptide as a Prognostic Indicator in Patients With Primary Pulmonary Hypertension
Circulation,
August 22, 2000;
102(8):
865 - 870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. MIYAMOTO, N. NAGAYA, T. SATOH, S. KYOTANI, F. SAKAMAKI, M. FUJITA, N. NAKANISHI, and K. MIYATAKE
Clinical Correlates and Prognostic Significance of Six-minute Walk Test in Patients with Primary Pulmonary Hypertension . Comparison with Cardiopulmonary Exercise Testing
Am. J. Respir. Crit. Care Med.,
February 1, 2000;
161(2):
487 - 492.
[Abstract]
[Full Text]
|
|
|
|
