Therapy in stable chronic obstructive pulmonary disease patients with pulmonary hypertension: a systematic review and meta-analysis

Abstract

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) without effective drugs to treat. We conducted a systematic review and meta-analysis in order to evaluate whether PH specific therapies were effective for stable COPD patients. Data were extracted from PubMed, Cochrane Central Register of Controlled Trials and China Knowledge Resource Integrated Database. Randomized controlled trials (RCTs) with PH specific therapy treated more than 4 weeks in COPD were selected. The main outcome was exercise capacity; meanwhile pulmonary arterial pressure (PAP), hypoxemia and health related life quality were also measured. We included nine trials involving 365 subjects, among which two were treated with bosentan and seven with sildenafil. The study time varied from 4 weeks to 18 months and mostly it was 12 weeks. In a pooled analysis of nine trials, exercise capacity of COPD patients was improved by PH-specific therapy [mean difference (MD) 66.39 m, 95% confidence intervals (CI): 59.44-73.34]. COPD with severe PH (mean PAP >35 mmHg by right heart catheterization or systolic PAP >50 mmHg by echocardiography) improved the exercise capacity (MD 67.24 m, 95% CI: 60.26-74.23), but COPD without PH at rest did not (MD -9.24 m, 95% CI: -75.08 to 56.31). Meanwhile PAP was decreased (MD -9.02 mmHg, 95% CI: -10.71 to -7.34 mmHg). Although hypoxemia and life quality were not improved, the dyspnea was alleviated or at least not aggravated (Borg dyspnea index, MD -0.86, 95% CI: -1.86 to 0.14). In conclusion, PH specific drugs (especially sildenafil) could improve exercise capacity and decrease PAP in COPD patients with severe PH.

Keywords: Chronic obstructive pulmonary disease (COPD); exercise capacity; pulmonary arterial pressure (PAP); pulmonary hypertension (PH); treatment.

Figure 1

Flowchart of study selection. *Vasodilator agents are three kinds of specific pulmonary vasodilators which are used in PH especially for IPAH, namely PDE-5 inhibitors, ERAs or prostacyclin analogs. Abbreviations: PH, pulmonary hypertension; IPH, idiopathic pulmonary arterial hypertension; PDE-5, phosphodiesterase-5; ERAs, endothelin receptor antagonists.

Figure 2

Risk of bias assessment for the randomized controlled trials included in the meta-analysis.

Figure 3

Heterogeneity (I²) and test for overall effect of PH specific drug on exercise capacity in COPD patients and subgroup analysis. Abbreviations: PH, pulmonary hypertension; COPD, chronic obstructive pulmonary disease.

Figure 4

Meta-analysis of different drugs on exercise capacity of COPD patients. Abbreviations: PH, pulmonary hypertension; COPD, chronic obstructive pulmonary disease; CI, confidence intervals.

Figure 5

The studies measured PAP, mean difference, 95% CI and forest plot in the meta-analysis. Abbreviations: PH, pulmonary hypertension; PAP, pulmonary arterial pressure; CI, confidence intervals.

Figure 6

Analysis of arterial partial pressure of oxygen (PaO₂) for the improvement of hypoxia. Abbreviations: PH, pulmonary hypertension; CI, confidence intervals.

Figure 7

To analyze the dyspnea with Borg index in two studies with PH specific therapy. Abbreviations: PH, pulmonary hypertension; CI, confidence intervals.

Figure 8

Evaluate health-related life-of-quality with SGRQ in COPD associated PH patients. Abbreviations: SGRQ, St. George’s Respiratory Questionnaire; COPD, chronic obstructive pulmonary disease; CI, confidence intervals.