Original Research: Diffuse Lung Disease |

Sildenafil Preserves Exercise Capacity in Patients With Idiopathic Pulmonary Fibrosis and Right-sided Ventricular DysfunctionSildenafil in Fibrosis, Ventricular Dysfunction

MeiLan K. Han, MD; David S. Bach, MD; Peter G. Hagan, MD; Eric Yow, MS; Kevin R. Flaherty, MD, FCCP; Galen B. Toews, MD; Kevin J. Anstrom, PhD; Fernando J. Martinez, MD, FCCP; for the IPFnet Investigators*
Author and Funding Information

From the University of Michigan Health System (Drs Han, Bach, Hagan, Flaherty, Toews, and Martinez), Ann Arbor, MI; and Duke Clinical Research Institute (Mr Yow and Dr Anstrom), Durham, NC.

Correspondence to: MeiLan K. Han, MD, Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 3916 Taubman Center, Box 5360, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5360; e-mail: mrking@umich.edu


A complete list of study participants is located in e-Appendix 1.

Funding/Support: This work is supported by funding from National Institutes of Health/National Heart, Lung and Blood Institute [Grants K23 HL093351 and U10HL080509 (data coordinating center), U10HL80413, U10HL80274, U10HL80370, U10HL80371, U10HL80383, U10HL80411, U10HL80509, U10HL80510, U10HL80513, U10HL80543, U10HL80571, and U10HL80685 (clinical centers)]; by the Cowlin Fund at the Chicago Community Trust; by Pfizer Inc, which donated sildenafil and matching placebo; and by Masimo Corp, which donated pulse oximeters.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Chest. 2013;143(6):1699-1708. doi:10.1378/chest.12-1594
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Background:  Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with pulmonary vasculopathy.

Objective:  The purpose of this study was to determine whether sildenafil improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction.

Methods:  The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by carbon monoxide diffusing capacity < 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment, and changes in 6MWD, St. George’s Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks.

Results:  The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafil experienced less decrement in 6MWD (99.3 m; P = .01) and greater improvement in SGRQ (13.4 points; P = .005) and EuroQol visual analog scores (17.9 points; P = .04) than subjects receiving placebo. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (P = .13), but was associated with greater relative improvement in SGRQ (14.8 points; P = .02) vs subjects receiving placebo. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36.

Conclusions:  Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafil also improves quality of life in subjects with RVH and RVSD.

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