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Original Research: Pulmonary Vascular Disease |

Comparative Effectiveness and Safety of Drug Therapy for Pulmonary Arterial HypertensionDrug Therapy for Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

Remy R. Coeytaux, MD, PhD; Kristine M. Schmit, MD, MPH; Bryan D. Kraft, MD; Andrzej S. Kosinski, PhD; Alicea M. Mingo, MD, MPH; Lisa M. Vann, MD; Daniel L. Gilstrap, MD; C. William Hargett, MD; Brooke Heidenfelder, PhD; Rowena J. Dolor, MD, MHS; Douglas C. McCrory, MD, MHS
Author and Funding Information

From the Department of Community and Family Medicine (Drs Coeytaux and Schmit), the Division of Pulmonary Medicine (Drs Kraft, Gilstrap, and Hargett), and the Department of Biostatistics and Bioinformatics (Dr Kosinski), Duke University School of Medicine; the Duke Evidence-based Practice Center (Drs Coeytaux, Heidenfelder, Dolor, and McCrory), Duke Clinical Research Institute, Duke University; the United States Navy (Dr Mingo); the Division of Hospital Medicine (Dr Vann), and the Division of General Internal Medicine (Drs Dolor and McCrory), Department of Medicine, Duke University Medical Center; and the Center for Health Services Research in Primary Care (Drs Dolor and McCrory), Department of Veterans Affairs, Durham, NC.

Correspondence to: Remy R. Coeytaux, MD, PhD, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC, 27705; e-mail: remy.coeytaux@dm.duke.edu


Funding/Support: This project was funded under the Agency for Healthcare Research and Quality, US Department of Health and Human Services [Contract No. 290-2007-10066-I].

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


Chest. 2014;145(5):1055-1063. doi:10.1378/chest.13-1864
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Background:  Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality.

Methods:  We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability.

Results:  We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively).

Conclusions:  Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.

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