Background:
Majority of the trials conducted on the effects of pulmonary artery hypertension specific therapies (PAH-ST) are short-term. The long-term effects of these agents on clinical outcomes and mortality in PAH group 1 subjects remains unclear.
Methods:
9 randomized controlled trials evaluating PAH-ST for at least ≥ 24 weeks in patients with PAH group 1 were selected using MEDLINE, EMBASE and the CENTRAL (inception-Oct 2020). The primary outcome was all-cause mortality. The secondary outcomes were clinical worsening of PAH (composite as defined in each trial), PAH related hospitalizations, WHO class improvement, change in 6-minute walk distance (6MWD), discontinuation of drug due to adverse effects and drug related serious adverse events. Estimates were measured as random effects relative risk (RR) with a 95% confidence interval (CI). The sensitivity analysis was performed for all-cause mortality.
Results:
In analysis of 3,815 participants with a mean age of 47.8±4.9 years and mean follow-up of ~91 weeks, long-term use of PAH-ST did not significantly affect all-cause mortality (RR:0.93, 95%CI, 0.69-1.24, P=0.62, I2=12). PAH-specific therapies were associated with a significant 32% relative risk reduction in the clinical worsening of PAH (RR:0.68, 95%CI, 0.61-0.77, P<0.001, I2=20), and significant improvement in the 6MWD (Standard difference in mean: 0.19, 95%CI 0.12-0.25, P<0.001, I2=0). The PAH related hospitalizations (RR: 0.72, 95%CI, 0.52-1.01, P=0.06, I2=65) and WHO class improvement (RR:1.22, 95%CI, 0.97-1.54, P=0.09, I2=29) showed favorable trends which did not achieve statistical significance. There were significantly lower adverse events (RR:0.89, 95%CI, 0.80-0.99, P=0.04, I2=23); however, higher discontinuations (RR:1.66, 95%CI, 1.05-2.63, P=0.03, I2=76) among the active treatment cohort. The sensitivity analysis for all-cause mortality based on drug class, combination vs monotherapy and follow-up duration did not demonstrate statistically significant difference.
Conclusions:
The long-term use of PAH-ST resulted in clinical and functional improvement in subjects with PAH group 1, but it did not reduce the all-cause mortality.