A meta-analysis of randomized controlled trials in pulmonary arterial hypertension

Abstract

Aims: There is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition.

Methods and results: Trials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35-0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39-1.00; P = 0.048).

Conclusion: The results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.

Figure 1

Flow chart of the search strategy and selection of the trials.

Figure 2

Cumulative RR estimate of death in active treatment groups when compared with control groups (RR [95% CI]). P = 0.023 for the overall estimate of the primary analysis by inverse variance method. Studies with no events in both groups (Table 3) were excluded.

Figure 3

Cumulative RR estimate of death in active treatment groups when compared with control groups stratified according to treatment class (inverse variance method). Heterogeneity between groups: P = 0.771. Studies with no events in both groups (Table 3) were excluded. RR, relative risk.

Figure 4

Cumulative RR estimate of death in active treatment groups when compared with control groups stratified by the median of baseline exercise capacity of the studies (inverse variance method). Studies with no events in both groups (Table 3) were excluded. Heterogeneity between groups: P = 0.825. 6MWD, six-minute walk distance; RR, relative risk.

Figure 5

Cumulative RR estimate of hospitalizations in active treatment groups when compared with control groups. P < 0.001 for the overall estimate by inverse variance method. Studies with no events in both groups (Table 3) were excluded. RR, relative risk.