Long-term outcomes in pulmonary arterial hypertension by functional class: a meta-analysis of randomized controlled trials and observational registries

• Type of Material: Article
• Authors: Nick H. Kim, University of California, San Diego; Micah Fisher, Emory University; David Poch, University of California, San Diego; Carol Zhao, Janssen Pharmaceuticals, Inc.; Mehul Shah, Janssen Pharmaceuticals, Inc.; Sonja Bartolome, University of Texas Southwestern Medical Center
• Language: English
• Date: 2020-10-01
• Publisher: SAGE PUBLICATIONS INC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1177/2045894020935291
• Title of Journal or Parent Work: PULMONARY CIRCULATION
• Volume: 10
• Issue: 4
• Start Page: 2045894020935291
• End Page: 2045894020935291
• Grant/Funding Information: Funding for this analysis was provided by Janssen Pharmaceuticals, Inc.
• Keywords: Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; functional class; meta-analysis; Science & Technology; Life Sciences & Biomedicine; mortality; Respiratory System; clinical worsening; morbidity; pulmonary arterial hypertension
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Limited data about the long-term prognosis and response to therapy in pulmonary arterial hypertension patients with World Health Organization functional class I/II symptoms are available. PubMed and Embase were searched for publications of observational registries and randomized, controlled trials in pulmonary arterial hypertension patients published between January 2001 and January 2018. Eligible registries enrolled pulmonary arterial hypertension patients ≥18 years, N > 30, and reported survival by functional class. Randomized, controlled trial inclusion criteria were pulmonary arterial hypertension patients ≥18 years, ≥6 months of treatment, and morbidity, mortality, or time to worsening as end points reported by functional class. The primary outcomes were survival for registries and clinical event rates for randomized, controlled trials. Separate random effects models were calculated for registries and randomized, controlled trials. Four randomized, controlled trials (n = 2482) and 10 registries (n = 6580) were included. Registries enrolled 9%–47% functional class I/II patients (the vast majority being functional class II) with various pulmonary arterial hypertension etiologies. Survival rates for functional class I/II patients at one, 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 for the 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 and 0.62 (95% CI: 0.49–0.78) for functional class III/IV. The calculated risk of death of 22% within three years for functional class I/II patients underlines the need for careful assessment and optimal treatment of patients with functional class I/II disease. The randomized, controlled trial analysis demonstrates that current medical therapies have a beneficial treatment effect in this population.