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:

• Oudiz, R. J., Galie, N., Olschewski, H., Torres, F., Frost, A., Ghofrani, H. A., Badesch, D. B., McGoon, M. D., McLaughlin, V. V., Roecker, E. B., Harrison, B. C., Despain, D., Dufton, C., Rubin, L. J., for the ARIES Study Group, (2009). Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension.. J Am Coll Cardiol 54: 1971-1981 [Abstract] [Full Text]  
• Archer, S. L., Michelakis, E. D. (2009). Phosphodiesterase Type 5 Inhibitors for Pulmonary Arterial Hypertension. NEJM 361: 1864-1871 [Full Text]  
• Vardi, Y. (2009). Microvascular Complications in Diabetic Erectile Dysfunction: Do we need other alternatives?. Diabetes Care 32: S420-S422 [Full Text]  
• Gruenig, E., Michelakis, E., Vachiery, J.-L., Vizza, C. D., Meyer, F. J., Doelberg, M., Bach, D., Dingemanse, J., Galie, N. (2009). Acute Hemodynamic Effects of Single-Dose Sildenafil When Added to Established Bosentan Therapy in Patients With Pulmonary Arterial Hypertension: Results of the COMPASS-1 Study. J Clin Pharmacol 49: 1343-1352 [Abstract] [Full Text]  
• Dussault, S., Maingrette, F., Menard, C., Michaud, S.-E., Haddad, P., Groleau, J., Turgeon, J., Perez, G., Rivard, A. (2009). Sildenafil Increases Endothelial Progenitor Cell Function and Improves Ischemia-Induced Neovascularization in Hypercholesterolemic Apolipoprotein E-Deficient Mice. Hypertension 54: 1043-1049 [Abstract] [Full Text]  
• Authors/Task Force Members, , Galie, N., Hoeper, M. M., Humbert, M., Torbicki, A., Vachiery, J.-L., Barbera, J. A., Beghetti, M., Corris, P., Gaine, S., Gibbs, J. S., Gomez-Sanchez, M. A., Jondeau, G., Klepetko, W., Opitz, C., Peacock, A., Rubin, L., Zellweger, M., Simonneau, G., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Auricchio, A., Bax, J., Ceconi, C., Dean, V., Filippatos, G., Funck-Brentano, C., Hobbs, R., Kearney, P., McDonagh, T., McGregor, K., Popescu, B. A., Reiner, Z., Sechtem, U., Sirnes, P. A., Tendera, M., Vardas, P., Widimsky, P., Document Reviewers, , Sechtem, U., Al Attar, N., Andreotti, F., Aschermann, M., Asteggiano, R., Benza, R., Berger, R., Bonnet, D., Delcroix, M., Howard, L., Kitsiou, A. N, Lang, I., Maggioni, A., Nielsen-Kudsk, J. E., Park, M., Perrone-Filardi, P., Price, S., Domenech, M. T. S., Vonk-Noordegraaf, A., Zamorano, J. L. (2009). Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30: 2493-2537 [Full Text]  
• Szabo, G., Radovits, T., Veres, G., Krieger, N., Loganathan, S., Sandner, P., Karck, M. (2009). Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass. Eur. J. Cardiothorac. Surg. 36: 657-664 [Abstract] [Full Text]  
• Jing, Z-C, Jiang, X, Wu, B-X, Xu, X-Q, Wu, Y, Ma, C-R, Wang, Y, Yang, Y-J, Pu, J-L, Gao, W (2009). Vardenafil treatment for patients with pulmonary arterial hypertension: a multicentre, open-label study. Heart 95: 1531-1536 [Abstract] [Full Text]  
• Hekier, E., Mandel, J. (2009). A 22-Year-Old Woman With Unexplained Dyspnea. Chest 136: 867-876 [Full Text]  
• Peacock, A. J., Naeije, R., Galie, N., Rubin, L. (2009). End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?. Eur Respir J 34: 231-242 [Abstract] [Full Text]  
• Toyooka, S., Kusano, K. F., Goto, K., Masaomi, Y., Oto, T., Sano, Y., Fuke, S., Okazaki, M., Ohe, T., Kasahara, S., Sano, S., Date, H. (2009). Right but not left ventricular function recovers early after living-donor lobar lung transplantation in patients with pulmonary arterial hypertension. J. Thorac. Cardiovasc. Surg. 138: 222-226 [Abstract] [Full Text]  
• SCHOINDRE, Y., MEUNE, C., DINH-XUAN, A. T., AVOUAC, J., KAHAN, A., ALLANORE, Y. (2009). Lack of Specificity of the 6-Minute Walk Test as an Outcome Measure for Patients with Systemic Sclerosis. The Journal of Rheumatology 36: 1481-1485 [Abstract] [Full Text]  
• Badesch, D. B., Champion, H. C., Gomez Sanchez, M. A., Hoeper, M. M., Loyd, J. E., Manes, A., McGoon, M., Naeije, R., Olschewski, H., Oudiz, R. J., Torbicki, A. (2009). Diagnosis and assessment of pulmonary arterial hypertension.. J Am Coll Cardiol 54: S55-S66 [Abstract] [Full Text]  
• Barst, R. J., Gibbs, J. S. R., Ghofrani, H. A., Hoeper, M. M., McLaughlin, V. V., Rubin, L. J., Sitbon, O., Tapson, V. F., Galie, N. (2009). Updated evidence-based treatment algorithm in pulmonary arterial hypertension.. J Am Coll Cardiol 54: S78-S84 [Abstract] [Full Text]  
• McLaughlin, V. V., Badesch, D. B., Delcroix, M., Fleming, T. R., Gaine, S. P., Galie, N., Gibbs, J. S. R., Kim, N. H., Oudiz, R. J., Peacock, A., Provencher, S., Sitbon, O., Tapson, V. F., Seeger, W. (2009). End Points and Clinical Trial Design in pulmonary arterial hypertension.. J Am Coll Cardiol 54: S97-107 [Abstract] [Full Text]  
• Galie, N., Brundage, B. H., Ghofrani, H. A., Oudiz, R. J., Simonneau, G., Safdar, Z., Shapiro, S., White, R. J., Chan, M., Beardsworth, A., Frumkin, L., Barst, R. J., on behalf of the Pulmonary Arterial Hypertension a, (2009). Tadalafil Therapy for Pulmonary Arterial Hypertension. Circulation 119: 2894-2903 [Abstract] [Full Text]  
• Laumanns, I. P., Fink, L., Wilhelm, J., Wolff, J.-C., Mitnacht-Kraus, R., Graef-Hoechst, S., Stein, M. M., Bohle, R. M., Klepetko, W., Hoda, M. A. R., Schermuly, R. T., Grimminger, F., Seeger, W., Voswinckel, R. (2009). The Noncanonical WNT Pathway Is Operative in Idiopathic Pulmonary Arterial Hypertension. Am. J. Respir. Cell Mol. Bio. 40: 683-691 [Abstract] [Full Text]  
• Barnett, C. F., Bonura, E. J., Nathan, S. D., Ahmad, S., Shlobin, O. A., Osei, K., Zaiman, A. L., Hassoun, P. M., Moller, D. R., Barnett, S. D., Girgis, R. E. (2009). Treatment of Sarcoidosis-Associated Pulmonary Hypertension: A Two-Center Experience. Chest 135: 1455-1461 [Abstract] [Full Text]  
• Vonk, M C, Broers, B, Heijdra, Y F, Ton, E, Snijder, R, van Dijk, A P J, van Laar, J M, Bootsma, H, van Hal, P T. W, van den Hoogen, F H J, van Daele, P L A (2009). Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study. Ann Rheum Dis 68: 961-965 [Abstract] [Full Text]  
• McLaughlin, V., Humbert, M., Coghlan, G., Nash, P., Steen, V. (2009). Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford) 48: iii25-iii31 [Abstract] [Full Text]  
• Faughnan, M. E., Granton, J. T., Young, L. H. (2009). The pulmonary vascular complications of hereditary haemorrhagic telangiectasia. Eur Respir J 33: 1186-1194 [Abstract] [Full Text]  
• Wang, T., Liu, Y., Chen, L., Wang, X., Hu, X-R., Feng, Y-L., Liu, D-S., Xu, D., Duan, Y-P., Lin, J., Ou, X-M., Wen, F-Q. (2009). Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur Respir J 33: 1122-1132 [Abstract] [Full Text]  
• Roberts, K. E., Fallon, M. B., Krowka, M. J., Brown, R. S., Trotter, J. F., Peter, I., Tighiouart, H., Knowles, J. A., Rabinowitz, D., Benza, R. L., Badesch, D. B., Taichman, D. B., Horn, E. M., Zacks, S., Kaplowitz, N., Kawut, S. M., for the Pulmonary Vascular Complications of Liver, (2009). Genetic Risk Factors for Portopulmonary Hypertension in Patients with Advanced Liver Disease. Am. J. Respir. Crit. Care Med. 179: 835-842 [Abstract] [Full Text]  
• Kowal-Bielecka, O, Landewe, R, Avouac, J, Chwiesko, S, Miniati, I, Czirjak, L, Clements, P, Denton, C, Farge, D, Fligelstone, K, Foldvari, I, Furst, D E, Muller-Ladner, U, Seibold, J, Silver, R M, Takehara, K, Toth, B G., Tyndall, A, Valentini, G, van den Hoogen, F, Wigley, F, Zulian, F, Matucci-Cerinic, M., and the EUSTAR co-authors, (2009). EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68: 620-628 [Abstract] [Full Text]  
• McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., Mathier, M. A., McGoon, M. D., Park, M. H., Rosenson, R. S., Rubin, L. J., Tapson, V. F., Varga, J. (2009). ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association Developed in Collaboration With the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 53: 1573-1619 [Full Text]  
• Writing Committee Members, , McLaughlin, V. V., Archer, S. L., Badesch, D. B., Barst, R. J., Farber, H. W., Lindner, J. R., Mathier, M. A., McGoon, M. D., Park, M. H., Rosenson, R. S., Rubin, L. J., Tapson, V. F., Varga, J. (2009). ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: Developed in Collaboration With the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 119: 2250-2294 [Full Text]  
• Woyda, K., Koebrich, S., Reiss, I., Rudloff, S., Pullamsetti, S. S., Ruhlmann, A., Weissmann, N., Ghofrani, H. A., Gunther, A., Seeger, W., Grimminger, F., Morty, R. E., Schermuly, R. T. (2009). Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia. Eur Respir J 33: 861-870 [Abstract] [Full Text]  
• Grimminger, F., Weimann, G., Frey, R., Voswinckel, R., Thamm, M., Bolkow, D., Weissmann, N., Muck, W., Unger, S., Wensing, G., Schermuly, R. T., Ghofrani, H.A. (2009). First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 33: 785-792 [Abstract] [Full Text]  
• Kuhn, M. (2009). Cardiac anti-remodelling effects of phosphodiesterase type 5 inhibitors: afterload-(in)dependent?. Cardiovasc Res 82: 4-6 [Full Text]  
• Schafer, S., Ellinghaus, P., Janssen, W., Kramer, F., Lustig, K., Milting, H., Kast, R., Klein, M. (2009). Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling. Cardiovasc Res 82: 30-39 [Abstract] [Full Text]  
• Rich, S. (2009). The Effects of Vasodilators in Pulmonary Hypertension: Pulmonary Vascular or Peripheral Vascular?. Circ Heart Fail 2: 145-150 [Full Text]  
• Souza, R., Jardim, C. (2009). Trends in pulmonary arterial hypertension. ERR 18: 7-12 [Full Text]  
• Ghofrani, H. A., Grimminger, F. (2009). Soluble guanylate cyclase stimulation: an emerging option in pulmonary hypertension therapy. ERR 18: 35-41 [Abstract] [Full Text]  
• Galie, N., Manes, A., Negro, L., Palazzini, M., Bacchi-Reggiani, M. L., Branzi, A. (2009). A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 30: 394-403 [Abstract] [Full Text]  
• Haworth, S G, Hislop, A A (2009). Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001-2006. Heart 95: 312-317 [Abstract] [Full Text]  
• McGoon, M. D., Kane, G. C. (2009). Pulmonary Hypertension: Diagnosis and Management. Mayo Clin Proc. 84: 191-207 [Abstract] [Full Text]  
• Zhu, B., Zhang, L., Alexeyev, M., Alvarez, D. F., Strada, S. J., Stevens, T. (2009). Type 5 phosphodiesterase expression is a critical determinant of the endothelial cell angiogenic phenotype. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L220-L228 [Abstract] [Full Text]  
• Lynch, J. P. III (2009). Idiopathic Pulmonary Fibrosis, Nonspecific Interstitial Pneumonia/Fibrosis, and Sarcoidosis. ACCP Pulmonary Med Brd Rev 25: 635-686 [Full Text]  
• Gilbert, C., Brown, M. C. J., Cappelleri, J. C., Carlsson, M., McKenna, S. P. (2009). Estimating a Minimally Important Difference in Pulmonary Arterial Hypertension Following Treatment With Sildenafil. Chest 135: 137-142 [Abstract] [Full Text]  
• Henkens, I. R., Gan, C. T.-J., van Wolferen, S. A., Hew, M., Boonstra, A., Twisk, J. W. R., Kamp, O., van der Wall, E. E., Schalij, M. J., Vonk Noordegraaf, A., Vliegen, H. W. (2008). ECG Monitoring of Treatment Response in Pulmonary Arterial Hypertension Patients. Chest 134: 1250-1257 [Abstract] [Full Text]  
• Andersen, A., Nielsen, J. M., Peters, C. D., Schou, U. K., Sloth, E., Nielsen-Kudsk, J. E. (2008). Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. Eur J Heart Fail 10: 1158-1165 [Abstract] [Full Text]  
• Spence, R., Mandagere, A., Dufton, C., Venitz, J. (2008). Pharmacokinetics and Safety of Ambrisentan in Combination With Sildenafil in Healthy Volunteers. J Clin Pharmacol 48: 1451-1459 [Abstract] [Full Text]  
• Guazzi, M. (2008). Clinical Use of Phosphodiesterase-5 Inhibitors in Chronic Heart Failure. Circ Heart Fail 1: 272-280 [Full Text]  
• Simonneau, G., Rubin, L. J., Galie, N., Barst, R. J., Fleming, T. R., Frost, A. E., Engel, P. J., Kramer, M. R., Burgess, G., Collings, L., Cossons, N., Sitbon, O., Badesch, D. B., for the PACES Study Group, (2008). Addition of Sildenafil to Long-Term Intravenous Epoprostenol Therapy in Patients with Pulmonary Arterial Hypertension: A Randomized Trial. ANN INTERN MED 149: 521-530 [Abstract] [Full Text]  
• Baliga, R. S., Zhao, L., Madhani, M., Lopez-Torondel, B., Visintin, C., Selwood, D., Wilkins, M. R., MacAllister, R. J., Hobbs, A. J. (2008). Synergy between Natriuretic Peptides and Phosphodiesterase 5 Inhibitors Ameliorates Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 178: 861-869 [Abstract] [Full Text]  
• Peinado, V. I., Pizarro, S., Barbera, J. A. (2008). Pulmonary Vascular Involvement in COPD. Chest 134: 808-814 [Abstract] [Full Text]  
• Schermuly, R. T., Stasch, J-P., Pullamsetti, S. S., Middendorff, R., Muller, D., Schluter, K-D., Dingendorf, A., Hackemack, S., Kolosionek, E., Kaulen, C., Dumitrascu, R., Weissmann, N., Mittendorf, J., Klepetko, W., Seeger, W., Ghofrani, H. A., Grimminger, F. (2008). Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J 32: 881-891 [Abstract] [Full Text]  
• Philip, A., Ramchandani, S., Dorrance, K., Dorrance, C. (2008). Sildenafil-Induced Thrombocytopenia. ANN INTERN MED 149: 437-439 [Full Text]  
• 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]  
• Ghofrani, H. A., Wilkins, M. W., Rich, S. (2008). Uncertainties in the Diagnosis and Treatment of Pulmonary Arterial Hypertension. Circulation 118: 1195-1201 [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 BTS Interstitial Lung Disease Gui, (2008). Interstitial lung disease guideline. 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. Ther Adv Respir Dis 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. Ther Adv Respir Dis 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. Ther Adv Respir Dis 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]