Combination therapy in pulmonary arterial hypertension: a meta-analysis

Cardiology. 2011;120(3):157-65. doi: 10.1159/000334431. Epub 2011 Dec 29.


Objectives: It is unclear whether combination therapy is efficient and well tolerated in patients with pulmonary arterial hypertension (PAH). The objective was to analyze completed trials assessing the efficacy and safety of treating PAH with combination therapy.

Methods: We performed a meta-analysis of all randomized controlled combination therapy trials that evaluated efficacy and safety in PAH patients. Trials were identified in the Cochrane Library, EMBASE and PubMed databases, reviews and reference lists of relevant papers.

Results: Six trials with a total of 858 patients were included in the meta-analysis. Compared with the control group, combination therapy reduced clinical worsening [relative risk (RR) 0.48, 95% confidence interval (CI) 0.26-0.91, p = 0.023], increased the 6-min-walk distance significantly by 22.22 m, and reduced mean pulmonary arterial pressure, right atrial pressure and pulmonary vascular resistance. The incidence of serious adverse events was similar in the 2 groups (RR 1.17, 95% CI 0.40-3.42, p = 0.77). However, combination therapy did not influence mortality.

Conclusions: Treatment of PAH with combination therapy improves multiple clinical and hemodynamic outcomes, but it has no effect on mortality. The long-term efficacy and safety of combination therapy in PAH requires further study based on large and rational-designed controlled clinical trials.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Endothelin Receptor Antagonists
  • Familial Primary Pulmonary Hypertension
  • Hemodynamics / physiology
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / physiopathology
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Prostaglandins / therapeutic use
  • Publication Bias
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors
  • Prostaglandins