FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 353:2148-2157 November 17, 2005 Number 20 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article PubMed Citation

ABSTRACT

Background Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate–mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung.

Methods In this double-blind, placebo-controlled study, we randomly assigned 278 patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks. The primary end point was the change from baseline to week 12 in the distance walked in six minutes. The change in mean pulmonary-artery pressure and World Health Organization (WHO) functional class and the incidence of clinical worsening were also assessed, but the study was not powered to assess mortality. Patients completing the 12-week randomized study could enter a long-term extension study.

Results The distance walked in six minutes increased from baseline in all sildenafil groups; the mean placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil, respectively (P<0.001 for all comparisons). All sildenafil doses reduced the mean pulmonary-artery pressure (P=0.04, P=0.01, and P<0.001, respectively), improved the WHO functional class (P=0.003, P<0.001, and P<0.001, respectively), and were associated with side effects such as flushing, dyspepsia, and diarrhea. The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo. Among the 222 patients completing one year of treatment with sildenafil monotherapy, the improvement from baseline at one year in the distance walked in six minutes was 51 m.

Conclusions Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension.

Source Information

From the Institute of Cardiology, University of Bologna, Bologna, Italy (N.G., A.B.); University Hospital, Justus-Liebig-University, Giessen, Germany (H.A.G., F.G.); the Institute of Tuberculosis and Lung Disease, Warsaw, Poland (A.T., M.K.); Babies and Children's Hospital, Columbia Presbyterian Medical Center, New York (R.J.B.); the University of California at San Diego, La Jolla (L.J.R.); University of Colorado Health Sciences Center, Denver (D.B.); the University of Washington, Seattle (T.F.); Pfizer Global Research and Development, Sandwich, Kent, United Kingdom (T.P., G.B.); and Hôpital Antoine Béclère, Clamart, France (G.S.).

Address reprint requests to Dr. Galiè at the Institute of Cardiology, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy, or at n.galie{at}bo.nettuno.it.

Full Text of this Article

Related Letters:

Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension
Hoeper M. M., Welte T., Izbicki G., Rosengarten D., Picard E., Kuschner W. G., Galiè N., Rubin L. J., Simonneau G.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:1091-1093, Mar 9, 2006. Correspondence

This article has been cited by other articles:

• Rai, P. R., Cool, C. D., King, J. A. C., Stevens, T., Burns, N., Winn, R. A., Kasper, M., Voelkel, N. F. (2008). The Cancer Paradigm of Severe Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 178: 558-564 [Abstract] [Full Text]  
• Kuwano, K., Hashino, A., Noda, K., Kosugi, K., Kuwabara, K. (2008). A Long-Acting and Highly Selective Prostacyclin Receptor Agonist Prodrug, 2-{4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), Ameliorates Rat Pulmonary Hypertension with Unique Relaxant Responses of Its Active Form, {4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic Acid (MRE-269), on Rat Pulmonary Artery. J. Pharmacol. Exp. Ther. 326: 691-699 [Abstract] [Full Text]  
• Wells, A U, Hirani, N, on behalf of the British Thoracic Society Intersti, (2008). Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 63: v1-v58 [Full Text]  
• Denton, C P, Pope, J E, Peter, H-H, Gabrielli, A, Boonstra, A, van den Hoogen, F H J, Riemekasten, G, De Vita, S, Morganti, A, Dolberg, M, Berkani, O, Guillevin, L, (on behalf of the TRacleer Use in PAH associated w, (2008). Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis 67: 1222-1228 [Abstract] [Full Text]  
• Yuen, S. Y., Pope, J. E. (2008). Learning from past mistakes: assessing trial quality, power and eligibility in non-renal systemic lupus erythematosus randomized controlled trials. Rheumatology (Oxford) 47: 1367-1372 [Abstract] [Full Text]  
• Boutet, K., Montani, D., Jais, X., Yaici, A., Sitbon, O., Simonneau, G., Humbert, M. (2008). Review: Therapeutic advances in pulmonary arterial hypertension. Therapeutic Advances in Respiratory Disease 2: 249-265 [Abstract]  
• Hill, N. S., Preston, I. R., Roberts, K. E. (2008). Inoperable Chronic Thromboembolic Pulmonary Hypertension: Treatable With Medical Therapy. Chest 134: 221-223 [Full Text]  
• Nagayama, T., Zhang, M., Hsu, S., Takimoto, E., Kass, D. A. (2008). Sustained Soluble Guanylate Cyclase Stimulation Offsets Nitric-Oxide Synthase Inhibition to Restore Acute Cardiac Modulation by Sildenafil. J. Pharmacol. Exp. Ther. 326: 380-387 [Abstract] [Full Text]  
• Suntharalingam, J., Treacy, C. M., Doughty, N. J., Goldsmith, K., Soon, E., Toshner, M. R., Sheares, K. K., Hughes, R., Morrell, N. W., Pepke-Zaba, J. (2008). Long-term Use of Sildenafil in Inoperable Chronic Thromboembolic Pulmonary Hypertension. Chest 134: 229-236 [Abstract] [Full Text]  
• Frey, R., Muck, W., Unger, S., Artmeier-Brandt, U., Weimann, G., Wensing, G. (2008). Single-Dose Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of the Soluble Guanylate Cyclase Stimulator BAY 63-2521: An Ascending-Dose Study in Healthy Male Volunteers. J Clin Pharmacol 48: 926-934 [Abstract] [Full Text]  
• Hill, N. S., Preston, I. R., Roberts, K. E. (2008). Patients with Pulmonary Arterial Hypertension in Clinical Trials: Who Are They?. Proc Am Thorac Soc 5: 603-609 [Abstract] [Full Text]  
• Gomberg-Maitland, M. (2008). Traditional and Alternative Designs for Pulmonary Arterial Hypertension Trials. Proc Am Thorac Soc 5: 610-616 [Abstract] [Full Text]  
• Ventetuolo, C. E., Benza, R. L., Peacock, A. J., Zamanian, R. T., Badesch, D. B., Kawut, S. M. (2008). Surrogate and Combined End Points in Pulmonary Arterial Hypertension. Proc Am Thorac Soc 5: 617-622 [Abstract] [Full Text]  
• Wilkins, M. R., Wharton, J., Grimminger, F., Ghofrani, H. A. (2008). Phosphodiesterase inhibitors for the treatment of pulmonary hypertension. Eur Respir J 32: 198-209 [Abstract] [Full Text]  
• Nagendran, J., Gurtu, V., Fu, D. Z., Dyck, J. R.B., Haromy, A., Ross, D. B., Rebeyka, I. M., Michelakis, E. D. (2008). A dynamic and chamber-specific mitochondrial remodeling in right ventricular hypertrophy can be therapeutically targeted. J. Thorac. Cardiovasc. Surg. 136: 168-178 [Abstract] [Full Text]  
• Giardini, A., Balducci, A., Specchia, S., Gargiulo, G., Bonvicini, M., Picchio, F. M. (2008). Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Eur Heart J 29: 1681-1687 [Abstract] [Full Text]  
• Wojciak-Stothard, B (2008). New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular remodelling. Postgrad. Med. J. 84: 348-353 [Abstract] [Full Text]  
• Galie, N., Olschewski, H., Oudiz, R. J., Torres, F., Frost, A., Ghofrani, H. A., Badesch, D. B., McGoon, M. D., McLaughlin, V. V., Roecker, E. B., Gerber, M. J., Dufton, C., Wiens, B. L., Rubin, L. J., for the Ambrisentan in Pulmonary Arterial Hyperten, (2008). Ambrisentan for the Treatment of Pulmonary Arterial Hypertension: Results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy (ARIES) Study 1 and 2. Circulation 117: 3010-3019 [Abstract] [Full Text]  
• MacKnight, B., Martinez, E. A., Simon, B. A. (2008). Anesthetic Management of Patients With Pulmonary Hypertension. SEMIN CARDIOTHORAC VASC ANESTH 12: 91-96 [Abstract]  
• Shu Zhu, , White, R. E., Barman, S. A. (2008). Original Research: Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle. Therapeutic Advances in Respiratory Disease 2: 119-127 [Abstract]  
• Avouac, J, Wipff, J, Kahan, A, Allanore, Y (2008). Effects of oral treatments on exercise capacity in systemic sclerosis related pulmonary arterial hypertension: a meta-analysis of randomised controlled trials. Ann Rheum Dis 67: 808-814 [Abstract] [Full Text]  
• Wrishko, R. E., Dingemanse, J., Yu, A., Darstein, C., Phillips, D. L., Mitchell, M. I. (2008). Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects. J Clin Pharmacol 48: 610-618 [Abstract] [Full Text]  
• Chin, K. M., Rubin, L. J. (2008). Pulmonary arterial hypertension.. J Am Coll Cardiol 51: 1527-1538 [Abstract] [Full Text]  
• Rogliani, P., Mura, M., Assunta Porretta, M., Saltini, C. (2008). Review: New perspectives in the treatment of idiopathic pulmonary fibrosis. Therapeutic Advances in Respiratory Disease 2: 75-93 [Abstract]  
• Harris, A, Kagemann, L, Ehrlich, R, Ehrlich, Y, Lopez, C R, Purvin, V A (2008). The effect of sildenafil on ocular blood flow. Br. J. Ophthalmol. 92: 469-473 [Abstract] [Full Text]  
• Mathier, M. A., Zhang, J., Ramanathan, R. C. (2008). Dramatic Functional Improvement Following Bariatric Surgery in a Patient With Pulmonary Arterial Hypertension and Morbid Obesity. Chest 133: 789-792 [Abstract] [Full Text]  
• National Pulmonary Hypertension Centres of the UK, (2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Heart 94: i1-i41 [Full Text]  
• National Pulmonary Hypertension Centres of the UK, (2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax 63: ii1-ii41 [Full Text]  
• Moore, S. C., DeSantis, E. R. H. (2008). Treatment of complications associated with systemic sclerosis. Am J Health Syst Pharm 65: 315-321 [Abstract] [Full Text]  
• Ivy, D. D., Doran, A. K., Smith, K. J., Mallory, G. B. Jr, Beghetti, M., Barst, R. J., Brady, D., Law, Y., Parker, D., Claussen, L., Abman, S. H. (2008). Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension. J Am Coll Cardiol 51: 161-169 [Abstract] [Full Text]  
• Pepke-Zaba, J., Gilbert, C., Collings, L., Brown, M. C. J. (2008). Sildenafil Improves Health-Related Quality of Life in Patients With Pulmonary Arterial Hypertension. Chest 133: 183-189 [Abstract] [Full Text]  
• Wang, H., Ye, M., Robinson, H., Francis, S. H., Ke, H. (2008). Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil. Mol. Pharmacol. 73: 104-110 [Abstract] [Full Text]  
• Hemnes, A. R., Zaiman, A., Champion, H. C. (2008). PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L24-L33 [Abstract] [Full Text]  
• Wryobeck, J. M., Lippo, G., McLaughlin, V., Riba, M., Rubenfire, M. (2007). Psychosocial Aspects of Pulmonary Hypertension: A Review. Psychosomatics 48: 467-475 [Abstract] [Full Text]  
• Thenappan, T., Shah, S. J., Rich, S., Gomberg-Maitland, M. (2007). A USA-based registry for pulmonary arterial hypertension: 1982 2006. Eur Respir J 30: 1103-1110 [Abstract] [Full Text]  
• Coghlan, J.G., Davar, J. (2007). How should we assess right ventricular function in 2008?. Eur Heart J Suppl 9: H22-H28 [Abstract] [Full Text]  
• Guazzi, M., Samaja, M., Arena, R., Vicenzi, M., Guazzi, M. D. (2007). Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure. J Am Coll Cardiol 50: 2136-2144 [Abstract] [Full Text]  
• Goldsmith, S. R. (2007). Type 5 Phosphodiesterase Inhibition in Heart Failure: The Next Step. J Am Coll Cardiol 50: 2145-2147 [Full Text]  
• Kass, D. A., Champion, H. C., Beavo, J. A. (2007). Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation. Circ. Res. 101: 1084-1095 [Abstract] [Full Text]  
• Reichenberger, F., Voswinckel, R., Enke, B., Rutsch, M., El Fechtali, E., Schmehl, T., Olschewski, H., Schermuly, R., Weissmann, N., Ghofrani, H. A., Grimminger, F., Mayer, E., Seeger, W. (2007). Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J 30: 922-927 [Abstract] [Full Text]  
• Girgis, R. E, Frost, A. E, Hill, N. S, Horn, E. M, Langleben, D., McLaughlin, V. V, Oudiz, R. J, Robbins, I. M, Seibold, J. R, Shapiro, S., Tapson, V. F, Barst, R. J (2007). Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. Ann Rheum Dis 66: 1467-1472 [Abstract] [Full Text]  
• Lewis, G. D., Shah, R., Shahzad, K., Camuso, J. M., Pappagianopoulos, P. P., Hung, J., Tawakol, A., Gerszten, R. E., Systrom, D. M., Bloch, K. D., Semigran, M. J. (2007). Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension. Circulation 116: 1555-1562 [Abstract] [Full Text]  
• Faoro, V., Huez, S., Giltaire, S., Pavelescu, A., van Osta, A., Moraine, J.-J., Guenard, H., Martinot, J.-B., Naeije, R. (2007). Effects of acetazolamide on aerobic exercise capacity and pulmonary hemodynamics at high altitudes. J. Appl. Physiol. 103: 1161-1165 [Abstract] [Full Text]  
• Patel, N. M., Lederer, D. J., Borczuk, A. C., Kawut, S. M. (2007). Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis. Chest 132: 998-1006 [Abstract] [Full Text]  
• Helman, D. L. Jr, Brown, A. W., Jackson, J. L., Shorr, A. F. (2007). Analyzing the Short-term Effect of Placebo Therapy in Pulmonary Arterial Hypertension: Potential Implications for the Design of Future Clinical Trials. Chest 132: 764-772 [Abstract] [Full Text]  
• Coggins, M. P., Bloch, K. D. (2007). Nitric Oxide in the Pulmonary Vasculature. Arterioscler. Thromb. Vasc. Bio. 27: 1877-1885 [Abstract] [Full Text]  
• Date, H., Kusano, K. F., Matsubara, H., Ogawa, A., Fujio, H., Miyaji, K., Okazaki, M., Yamane, M., Toyooka, S., Aoe, M., Sano, Y., Hanazaki, M., Goto, K., Kasahara, S., Sano, S., Ohe, T. (2007). Living-Donor Lobar Lung Transplantation for Pulmonary Arterial Hypertension After Failure of Epoprostenol Therapy. J Am Coll Cardiol 50: 523-527 [Abstract] [Full Text]  
• Kass, D. A. (2007). Hypertrophied Right Hearts Get Two for the Price of One: Can Inhibiting Phosphodiesterase Type 5 Also Inhibit Phosphodiesterase Type 3?. Circulation 116: 233-235 [Full Text]  
• Nagendran, J., Archer, S. L., Soliman, D., Gurtu, V., Moudgil, R., Haromy, A., St. Aubin, C., Webster, L., Rebeyka, I. M., Ross, D. B., Light, P. E., Dyck, J. R.B., Michelakis, E. D. (2007). Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility. Circulation 116: 238-248 [Abstract] [Full Text]  
• Kass, D. A., Takimoto, E., Nagayama, T., Champion, H. C. (2007). Phosphodiesterase regulation of nitric oxide signaling. Cardiovasc Res 75: 303-314 [Abstract] [Full Text]  
• Tidswell, M., Higgins, T. L. (2007). The Anesthesiologist and Pulmonary Arterial Hypertension. SEMIN CARDIOTHORAC VASC ANESTH 11: 93-95  
• Jain, S., Ventura, H., deBoisblanc, B. (2007). Pathophysiology of Pulmonary Arterial Hypertension. SEMIN CARDIOTHORAC VASC ANESTH 11: 104-109 [Abstract]  
• Yung, G. (2007). Lung Transplantation and Pulmonary Hypertension. SEMIN CARDIOTHORAC VASC ANESTH 11: 149-156 [Abstract]  
• Badesch, D. B., Abman, S. H., Simonneau, G., Rubin, L. J., McLaughlin, V. V. (2007). Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines. Chest 131: 1917-1928 [Abstract] [Full Text]  
• Frazier, A. A., Franks, T. J., Mohammed, T.-L. H., Ozbudak, I. H., Galvin, J. R. (2007). From the Archives of the AFIP: Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis. RadioGraphics 27: 867-882 [Abstract] [Full Text]  
• Schermuly, R. T., Pullamsetti, S. S., Kwapiszewska, G., Dumitrascu, R., Tian, X., Weissmann, N., Ghofrani, H. A., Kaulen, C., Dunkern, T., Schudt, C., Voswinckel, R., Zhou, J., Samidurai, A., Klepetko, W., Paddenberg, R., Kummer, W., Seeger, W., Grimminger, F. (2007). Phosphodiesterase 1 Upregulation in Pulmonary Arterial Hypertension: Target for Reverse-Remodeling Therapy. Circulation 115: 2331-2339 [Abstract] [Full Text]  
• Wang, X.-X., Zhang, F.-R., Shang, Y.-P., Zhu, J.-H., Xie, X.-D., Tao, Q.-M., Zhu, J.-H., Chen, J.-Z. (2007). Transplantation of Autologous Endothelial Progenitor Cells May Be Beneficial in Patients With Idiopathic Pulmonary Arterial Hypertension: A Pilot Randomized Controlled Trial. J Am Coll Cardiol 49: 1566-1571 [Abstract] [Full Text]  
• Wang, H., Liu, Y., Hou, J., Zheng, M., Robinson, H., Ke, H. (2007). From the Cover: Structural insight into substrate specificity of phosphodiesterase 10. Proc. Natl. Acad. Sci. USA 104: 5782-5787 [Abstract] [Full Text]  
• Thomas, B. G., Maloney, J. D. (2007). Use of silfenadil for treatment of respiratory distress after pneumonectomy for bronchogenic carcinoma. ICVTS 6: 262-263 [Abstract] [Full Text]  
• Forfia, P. R., Lee, M., Tunin, R. S., Mahmud, M., Champion, H. C., Kass, D. A. (2007). Acute Phosphodiesterase 5 Inhibition Mimics Hemodynamic Effects of B-Type Natriuretic Peptide and Potentiates B-Type Natriuretic Peptide Effects in Failing But Not Normal Canine Heart. J Am Coll Cardiol 49: 1079-1088 [Abstract] [Full Text]  
• Hoeper, M. M. (2007). Observational trials in pulmonary arterial hypertension: low scientific evidence but high clinical value. Eur Respir J 29: 432-434 [Full Text]  
• Mathai, S. C., Girgis, R. E., Fisher, M. R., Champion, H. C., Housten-Harris, T., Zaiman, A., Hassoun, P. M. (2007). Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J 29: 469-475 [Abstract] [Full Text]  
• Diller, G.-P., Gatzoulis, M. A. (2007). Pulmonary Vascular Disease in Adults With Congenital Heart Disease. Circulation 115: 1039-1050 [Abstract] [Full Text]  
• Lewis, G. D., Lachmann, J., Camuso, J., Lepore, J. J., Shin, J., Martinovic, M. E., Systrom, D. M., Bloch, K. D., Semigran, M. J. (2007). Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure. Circulation 115: 59-66 [Abstract] [Full Text]  
• Klodell, C. T. Jr, Morey, T. E., Lobato, E. B., Aranda, J. M. Jr, Staples, E. D., Schofield, R. S., Hess, P. J., Martin, T. D., Beaver, T. M. (2007). Effect of Sildenafil on Pulmonary Artery Pressure, Systemic Pressure, and Nitric Oxide Utilization in Patients With Left Ventricular Assist Devices. Ann. Thorac. Surg. 83: 68-71 [Abstract] [Full Text]  
• Hoeper, M. M., Lee, S. H., Voswinckel, R., Palazzini, M., Jais, X., Marinelli, A., Barst, R. J., Ghofrani, H. A., Jing, Z.-C., Opitz, C., Seyfarth, H.-J., Halank, M., McLaughlin, V., Oudiz, R. J., Ewert, R., Wilkens, H., Kluge, S., Bremer, H.-C., Baroke, E., Rubin, L. J. (2006). Complications of Right Heart Catheterization Procedures in Patients With Pulmonary Hypertension in Experienced Centers. J Am Coll Cardiol 48: 2546-2552 [Abstract] [Full Text]  
• Shim, J. K., Choi, Y. S., Oh, Y. J., Kim, D. H., Hong, Y. W., Kwak, Y. L. (2006). Effect of oral sildenafil citrate on intraoperative hemodynamics in patients with pulmonary hypertension undergoing valvular heart surgery. J. Thorac. Cardiovasc. Surg. 132: 1420-1425 [Abstract] [Full Text]  
• Barst, R. J., Galie, N., Naeije, R., Simonneau, G., Jeffs, R., Arneson, C., Rubin, L. J. (2006). Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J 28: 1195-1203 [Abstract] [Full Text]  
• McLaughlin, V. V., Oudiz, R. J., Frost, A., Tapson, V. F., Murali, S., Channick, R. N., Badesch, D. B., Barst, R. J., Hsu, H. H., Rubin, L. J. (2006). Randomized Study of Adding Inhaled Iloprost to Existing Bosentan in Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 174: 1257-1263 [Abstract] [Full Text]  
• Distler, O., Behrens, F., Huscher, D., Foeldvari, I., Zink, A., Nash, P., Denton, C. P., Humbert, M., Matucci-Cerinic, M., Seibold, J., Rubin, L., Furst, D. E. (2006). Need for improved outcome measures in pulmonary arterial hypertension related to systemic sclerosis. Rheumatology (Oxford) 45: 1455-1457 [Full Text]  
• Blount, M. A., Zoraghi, R., Ke, H., Bessay, E. P., Corbin, J. D., Francis, S. H. (2006). A 46-Amino Acid Segment in Phosphodiesterase-5 GAF-B Domain Provides for High Vardenafil Potency over Sildenafil and Tadalafil and Is Involved in Phosphodiesterase-5 Dimerization. Mol. Pharmacol. 70: 1822-1831 [Abstract] [Full Text]  
• Faber, J. E., Szymeczek, C. L., Salvi, S. S., Zhang, H. (2006). Enhanced {alpha}1-adrenergic trophic activity in pulmonary artery of hypoxic pulmonary hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 291: H2272-H2281 [Abstract] [Full Text]  
• Mukhopadhyay, S., Sharma, M., Ramakrishnan, S., Yusuf, J., Gupta, M. D., Bhamri, N., Trehan, V., Tyagi, S. (2006). Phosphodiesterase-5 Inhibitor in Eisenmenger Syndrome: A Preliminary Observational Study. Circulation 114: 1807-1810 [Abstract] [Full Text]  
• Channick, R. N., Olschewski, H., Seeger, W., Staub, T., Voswinckel, R., Rubin, L. J. (2006). Safety and Efficacy of Inhaled Treprostinil as Add-On Therapy to Bosentan in Pulmonary Arterial Hypertension. J Am Coll Cardiol 48: 1433-1437 [Abstract] [Full Text]  
• Newman, J. H., Robbins, I. M. (2006). Exercise Training in Pulmonary Hypertension: Implications for the Evaluation of Drug Trials. Circulation 114: 1448-1449 [Full Text]  
• Mereles, D., Ehlken, N., Kreuscher, S., Ghofrani, S., Hoeper, M. M., Halank, M., Meyer, F. J., Karger, G., Buss, J., Juenger, J., Holzapfel, N., Opitz, C., Winkler, J., Herth, F. F.J., Wilkens, H., Katus, H. A., Olschewski, H., Grunig, E. (2006). Exercise and Respiratory Training Improve Exercise Capacity and Quality of Life in Patients With Severe Chronic Pulmonary Hypertension. Circulation 114: 1482-1489 [Abstract] [Full Text]  
• Gomberg-Maitland, M. (2006). Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: is more better?. Eur Respir J 28: 683-686 [Full Text]  
• Hoeper, M. M., Leuchte, H., Halank, M., Wilkens, H., Meyer, F. J., Seyfarth, H. J., Wensel, R., Ripken, F., Bremer, H., Kluge, S., Hoeffken, G., Behr, J. (2006). Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 28: 691-694 [Abstract] [Full Text]  
• Rich, S. (2006). The current treatment of pulmonary arterial hypertension: time to redefine success.. Chest 130: 1198-1202 [Abstract] [Full Text]  
• Fesler, P., Pagnamenta, A., Rondelet, B., Kerbaul, F., Naeije, R. (2006). Effects of sildenafil on hypoxic pulmonary vascular function in dogs. J. Appl. Physiol. 101: 1085-1090 [Abstract] [Full Text]  
• Said, S. I. (2006). Mediators and modulators of pulmonary arterial hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol. 291: L547-L558 [Abstract] [Full Text]  
• Ghofrani, H. A., Voswinckel, R., Reichenberger, F., Weissmann, N., Schermuly, R. T., Seeger, W., Grimminger, F. (2006). Hypoxia- and non-hypoxia-related pulmonary hypertension - Established and new therapies. Cardiovasc Res 72: 30-40 [Abstract] [Full Text]  
• Oliver, J. J., Melville, V. P., Webb, D. J. (2006). Effect of Regular Phosphodiesterase Type 5 Inhibition in Hypertension. Hypertension 48: 622-627 [Abstract] [Full Text]  
• Distler, O., Pignone, A. (2006). Pulmonary arterial hypertension and rheumatic diseases--from diagnosis to treatment. Rheumatology (Oxford) 45: iv22-iv25 [Abstract] [Full Text]  
• Kahler, C. M., Colleselli, D. (2006). Pulmonary arterial hypertension (PAH) in connective tissue diseases. Rheumatology (Oxford) 45: iii11-iii13 [Abstract] [Full Text]  
• Riemekasten, G., Sunderkotter, C. (2006). Vasoactive therapies in systemic sclerosis. Rheumatology (Oxford) 45: iii49-iii51 [Abstract] [Full Text]  
• McLaughlin, V. V., McGoon, M. D. (2006). Pulmonary Arterial Hypertension. Circulation 114: 1417-1431 [Full Text]  
• Krowka, M. J., Swanson, K. L. (2006). How should we treat portopulmonary hypertension?. Eur Respir J 28: 466-467 [Full Text]  
• Trow, T. K. (2006). Clinical Year in Review II: Occupational Lung Disease, Pulmonary Vascular Disease, Bronchiectasis, and Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 3: 557-560 [Full Text]