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. 2013 Aug 1;3(8):e003113.
doi: 10.1136/bmjopen-2013-003113.

Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials

Masataka Kuwana  1 , Hiroshi Watanabe, Nobushige Matsuoka, Naonobu Sugiyama
Affiliations

Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials

Masataka Kuwana et al. BMJ Open. .

Abstract

Objectives: 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.

Design: 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.

Setting: International.

Participants: Patients with PAH generally (n=3073) and CTD-PAH specifically (n=678).

Primary outcome measure: 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.

Keywords: THORACIC MEDICINE.

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Figures

Figure 1
Figure 1
Flow diagram summarising selection of studies evaluating treatments for patients with (A) all forms of pulmonary arterial hypertension (PAH) and (B) connective tissue disease-PAH. RCT, randomised controlled trial.
Figure 2
Figure 2
Effects of individual pulmonary arterial hypertension (PAH) agents on 6 min walk distance (6 MWD) in patients with any form of PAH. ERA, endothelin receptor antagonist; NA, not applicable; PDE, phosphodiesterase; PGI2, prostacyclin.
Figure 3
Figure 3
Effects of individual pulmonary arterial hypertension (PAH) agents on 6 min walk distance (6 MWD) in patients with PAH associated with connective tissue disease. ERA, endothelin receptor antagonist; NA, not applicable; PDE, phosphodiesterase; PGI2, prostacyclin. For single-arm studies, the mean changes from baseline are shown.
See this image and copyright information in PMC

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