A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology

Am Heart J. 2007 Jun;153(6):1037-47. doi: 10.1016/j.ahj.2007.02.037.


Background: Various innovative pharmacologic strategies for the treatment of patients with pulmonary hypertension have been tested in recent years. Neither their comparative efficacy on surrogate end points nor the overall impact on mortality have been formally reviewed.

Methods: We did a systematic overview of all randomized trials on the therapeutic yield of prostacyclin and analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors in patients with pulmonary hypertension searched in EMBASE, MEDLINE, and CINAHL databases from January 1985 to December 2005.

Results: Sixteen trials involving 1962 patients met the inclusion criteria. Up to 80% of the patients were in functional class III/IV with a median walking distance of 330 m at baseline. Overall, experimental treatments were associated with (1) a nonsignificant reduction in all-cause mortality (relative risk 0.70, 95% CI 0.41-1.22), (2) a minor but statistically significant improvement in exercise capacity of 42.8 m (95% CI 27.8-57.8), and (3) an improved dyspnea status by at least one functional class (relative risk 1.83, 95% CI 1.26-2.66). Changes in exercise capacity were not found to be predictive of a survival benefit.

Conclusions: Although confirming the limited benefits in clinical end points documented by each trial, the overview fails to support a significant survival advantage and does not support the predictive power of surrogate end points.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Endothelin Receptor Antagonists*
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / therapeutic use*
  • Exercise
  • Exercise Tolerance
  • Humans
  • Hypertension, Pulmonary / classification
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality*
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Predictive Value of Tests
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome


  • Endothelin Receptor Antagonists
  • Phosphodiesterase Inhibitors
  • Epoprostenol