Long-term outcomes in pulmonary arterial hypertension by functionalclass: a meta-analysis of randomized controlled trials and observationalregistries

摘要

Limited data about the long-term prognosis and response to therapy in pulmonaryarterial hypertension patients with World Health Organization functional classI/II symptoms are available. PubMed and Embase were searched for publications ofobservational registries and randomized, controlled trials in pulmonary arterialhypertension patients published between January 2001 and January 2018. Eligibleregistries enrolled pulmonary arterial hypertension patients ≥18 years,N > 30, and reported survival by functional class.Randomized, controlled trial inclusion criteria were pulmonary arterialhypertension patients ≥18 years, ≥6 months of treatment, and morbidity,mortality, or time to worsening as end points reported by functional class. Theprimary outcomes were survival for registries and clinical event rates forrandomized, controlled trials. Separate random effects models were calculatedfor registries and randomized, controlled trials. Four randomized, controlledtrials (n = 2482) and 10 registries (n = 6580)were included. Registries enrolled 9%–47% functional class I/II patients (thevast majority being functional class II) with various pulmonary arterialhypertension etiologies. Survival rates for functional class I/II patients atone, two, and three years were 93% (95% confidence interval (CI): 91%–95%), 86%(95% CI: 82%–89%), and 78% (95% CI: 73%–83%), respectively. The hazard ratio forthe treatment effect in randomized, controlled trials overall was 0.61 (95% CI:0.51–0.74) and 0.60 (95% CI: 0.44–0.82) for functional class I/II patients and0.62 (95% CI: 0.49–0.78) for functional class III/IV. The calculated risk ofdeath of 22% within three years for functional class I/II patients underlinesthe need for careful assessment and optimal treatment of patients withfunctional class I/II disease. The randomized, controlled trial analysisdemonstrates that current medical therapies have a beneficial treatment effectin this population.