title: Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials.
abstract: OBJECTIVE
  Few studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established.
  
  
  METHODS
  Meta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and August 2012 were eligible.
  
  
  METHODS
  International.
  
  
  METHODS
  Patients with PAH generally (n=3073) and CTD-PAH specifically (n=678).
  
  
  METHODS
  Exercise capacity (6 min walk distance, 6 MWD).
  
  
  RESULTS
  Patients with PAH (all forms) had mean age 32-55 years (women, 61-87%); CTD-PAH patients had mean age 45-55 years (women, 74-95%). Overall estimate of mean change in 6 MWD from baseline (95% CI) for the active treatment group versus the control group in all patients with PAH was 34.6 m (27.4-41.9 m). Pooled mean differences from the results for patients receiving placebo by subgroup of patients receiving phosphodiesterase (PDE)-5 inhibitors, endothelin receptor antagonists (ERAs) and prostacyclin (PGI2) analogues were 22.4-45.5, 39.5-44.2 and 12.4-64.9 m, respectively. Overall estimate of mean difference between changes in 6 MWD in patients with CTD-PAH was 34.2 m (23.3-45.0 m). Pooled mean differences by subgroup of patients receiving PDE-5 inhibitors, ERAs and PGI2 analogues in patients with CTD-PAH were 37.0-47.1, 14.1-21.7 and 21.0-108.0 m, respectively. ERAs were less effective in patients with CTD-PAH than all-form patients with PAH: 14.1 m (-4.4-32.6 m) vs 39.5 m (19.5-59.6 m) for bosentan and 21.7 m (2.2-41.3 m) vs 44.2 m (30.2-58.2 m) for ambrisentan.
  
  
  CONCLUSIONS
  All three types of PAH agent are effective. However, ERAs may be a less effective choice against CTD-PAH; further studies are needed. Limitations include the limited number of studies for some agents and for patients with CTD-PAH.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Nobushige
authors.initials: N
authors.lastname: Matsuoka
authors.forename: Naonobu
authors.initials: N
authors.lastname: Sugiyama
keywords: THORACIC MEDICINE
references.citation: Am Heart J. 2006 Apr;151(4):851.e1-5
references.pmid: 16569546
references.citation: J Heart Lung Transplant. 2010 Feb;29(2):137-49
references.pmid: 20022264
references.citation: J Am Coll Cardiol. 2002 May 1;39(9):1496-502
references.pmid: 11985913
references.citation: Circulation. 2008 Jun 10;117(23):3010-9
references.pmid: 18506008
references.citation: Chest. 2009 Jan;135(1):137-142
references.pmid: 18812447
references.citation: N Engl J Med. 2002 Mar 21;346(12):896-903
references.pmid: 11907289
references.citation: J Cardiovasc Pharmacol. 2003 Feb;41(2):293-9
references.pmid: 12548091
references.citation: Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):487-92
references.pmid: 10673190
references.citation: N Engl J Med. 2005 Nov 17;353(20):2148-57
references.pmid: 16291984
references.citation: Rheumatology (Oxford). 2010 Mar;49(3):490-500
references.pmid: 20015974
references.citation: Circ J. 2010 Jul;74(7):1458-64
references.pmid: 20519876
references.citation: Arthritis Rheum. 2005 Dec;52(12):3792-800
references.pmid: 16320330
references.citation: Eur Respir J. 2010 Sep;36(3):549-55
references.pmid: 20562126
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S97-S107
references.pmid: 19555863
references.citation: Am J Respir Crit Care Med. 2009 Jan 15;179(2):151-7
references.pmid: 18931333
references.citation: Am J Respir Crit Care Med. 2002 Mar 15;165(6):800-4
references.pmid: 11897647
references.citation: Ann Rheum Dis. 2006 Oct;65(10):1336-40
references.pmid: 16793845
references.citation: Ann Rheum Dis. 2003 Nov;62(11):1088-93
references.pmid: 14583573
references.citation: Ann Rheum Dis. 2012 Feb;71(2):249-52
references.pmid: 21998119
references.citation: Ann Rheum Dis. 2010 Jul;69(7):1360-3
references.pmid: 20472586
references.citation: Int Heart J. 2009 Jul;50(4):513-29
references.pmid: 19609055
references.citation: Med Sci Sports Exerc. 2008 Oct;40(10):1725-32
references.pmid: 18799981
references.citation: Chest. 2010 Dec;138(6):1383-94
references.pmid: 20507945
references.citation: BMJ. 2012 Jan 03;344:d7762
references.pmid: 22214758
references.citation: Am Heart J. 2010 Feb;159(2):245-57
references.pmid: 20152223
references.citation: Lancet. 2008 Jun 21;371(9630):2093-100
references.pmid: 18572079
references.citation: Circulation. 2006 Jul 4;114(1):48-54
references.pmid: 16801459
references.citation: N Engl J Med. 1996 Feb 1;334(5):296-301
references.pmid: 8532025
references.citation: Eur Respir J. 2006 Oct;28(4):691-4
references.pmid: 17012628
references.citation: J Rheumatol. 2007 Dec;34(12):2417-22
references.pmid: 17985403
references.citation: Respir Res. 2010 Jan 29;11:12
references.pmid: 20113497
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S43-S54
references.pmid: 19555858
references.citation: Chest. 2004 Aug;126(2):420-7
references.pmid: 15302727
references.citation: Lancet. 2001 Oct 6;358(9288):1119-23
references.pmid: 11597664
references.citation: Eur Heart J. 2009 Feb;30(4):394-403
references.pmid: 19155250
references.citation: Circulation. 2010 Jul 13;122(2):164-72
references.pmid: 20585012
references.citation: Cardiovasc Ther. 2012 Apr;30(2):93-9
references.pmid: 21884013
references.citation: Chest. 2003 Feb;123(2):344-50
references.pmid: 12576350
references.citation: Am J Respir Crit Care Med. 2006 Dec 1;174(11):1257-63
references.pmid: 16946127
references.citation: Circulation. 2009 Jun 9;119(22):2894-903
references.pmid: 19470885
references.citation: Ann Intern Med. 1990 Apr 1;112(7):485-91
references.pmid: 2107780
references.citation: Chest. 2010 Jun;137(6):1258-60
references.pmid: 20525647
references.citation: Ann Rheum Dis. 2008 Jun;67(6):808-14
references.pmid: 17901091
references.citation: Ann Intern Med. 2008 Oct 21;149(8):521-30
references.pmid: 18936500
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S55-S66
references.pmid: 19555859
references.citation: Circulation. 2010 Jul 13;122(2):156-63
references.pmid: 20585011
references.citation: J Am Coll Cardiol. 2002 Aug 21;40(4):780-8
references.pmid: 12204511
references.citation: Ann Intern Med. 2000 Mar 21;132(6):425-34
references.pmid: 10733441
references.citation: J Am Coll Cardiol. 2010 May 4;55(18):1915-22
references.pmid: 20430262
references.citation: Eur Heart J. 2010 Sep;31(17):2080-6
references.pmid: 20504865