PMID- 31722043 OWN - NLM STAT- MEDLINE DCOM- 20210531 LR - 20210531 IS - 1432-1750 (Electronic) IS - 0341-2040 (Print) IS - 0341-2040 (Linking) VI - 198 IP - 1 DP - 2020 Feb TI - The Role of Noninvasive Endpoints in Predicting Long-Term Outcomes in Pulmonary Arterial Hypertension. PG - 65-86 LID - 10.1007/s00408-019-00289-2 [doi] AB - BACKGROUND: Until recently, many clinical trials in patients with pulmonary arterial hypertension (PAH) evaluated exercise capacity with 6-minute walk distance (6MWD) as the primary endpoint. Common secondary endpoints include PAH functional class (FC), which assesses symptoms, and either brain natriuretic peptide (BNP) or the inactive N-terminal cleavage product of its prohormone (NT-proBNP), which assesses cardiac function. OBJECTIVE: Examine the relationships among 6MWD, FC, and BNP/NT-proBNP measured at baseline or follow-up with long-term outcomes in PAH studies. METHODS: Relevant literature from January 1990 to April 2018 were obtained by searching PubMed, Embase, and Cochrane. Articles in English reporting on associations between 6MWD, FC, or BNP/NT-proBNP and outcomes in PAH were identified. Each endpoint was evaluated individually. Prespecified inclusion and exclusion criteria were applied at level 1 (titles/abstracts) and level 2 (full-text review). RESULTS: The database search yielded 836 unique records; 65 full-text articles were reviewed. Twenty-five studies were eligible for inclusion. Findings supported the importance of measuring PAH noninvasive endpoints in predicting long-term outcomes. Patients with shorter or decreased 6MWD, poor (III/IV) or declining FC (e.g., from II to III), or elevated or increasing BNP/NT-proBNP had a higher risk of death and costly events (e.g., hospitalization, lung transplant). FC also predicted health care resource utilization and costs. Collectively, these endpoints establish risk groups that predict likelihood of complications from PAH or death. CONCLUSION: Assessment of 6MWD, FC, and BNP/NT-proBNP provides low-cost, efficient, and noninvasive means of predicting long-term health and economic outcomes in patients with PAH. FAU - Wronski, Samantha L AU - Wronski SL AD - RTI Health Solutions, Research Triangle Park, NC, USA. FAU - Mordin, Margaret AU - Mordin M AUID- ORCID: 0000-0002-6048-0275 AD - RTI Health Solutions, Ann Arbor, MI, USA. mmordin@rti.org. FAU - Kelley, Kim AU - Kelley K AD - Rx Trusted Advisors, Phoenix, AZ, USA. FAU - Anguiano, Rebekah H AU - Anguiano RH AD - Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA. FAU - Classi, Peter AU - Classi P AD - United Therapeutics, Research Triangle Park, NC, USA. FAU - Shen, Eric AU - Shen E AD - United Therapeutics, Research Triangle Park, NC, USA. FAU - Manaker, Scott AU - Manaker S AD - Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20191113 PL - United States TA - Lung JT - Lung JID - 7701875 RN - 0 (Biomarkers) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM MH - Biomarkers/blood MH - Disease Progression MH - *Functional Status MH - Hospitalization/statistics & numerical data MH - Humans MH - Lung Transplantation/statistics & numerical data MH - Mortality MH - Natriuretic Peptide, Brain/*blood MH - Outcome Assessment, Health Care MH - Peptide Fragments/*blood MH - Prognosis MH - Pulmonary Arterial Hypertension/blood/mortality/*physiopathology MH - Severity of Illness Index MH - *Walk Test PMC - PMC7012965 OTO - NOTNLM OT - Noninvasive endpoint OT - PAH OT - Risk assessment COIS- Samantha Wronski and Margaret Mordin are employees of RTI Health Solutions. Kim Kelley is business owner of Rx Trusted Advisors, PLLC which works with life science and futurist groups, along with peer to peer learning, pipeline strategy sessions. And additional work advising in high cost pharmacy and medical cases. Previous Director of Pharmacy for BlueCross and BlueShield of Arizona. Groups and organizations I have worked directly or indirectly with or own stock include; Rx Worldwide Meetings, Navigant Life Sciences, Amgen, Novartis, UCB, Gerson Lehrman Group Councel, Lilly, United Therapeutics Corporation, CB Partner, McCann Health, ClearView Health Partners, Parallax Life Sciences, Insmed, Integrated Healthcare Management, Business Talent Group, Evidera, and River West Meeting Associates. Dr. Anguiano is on the speaker's bureau and advisory board for United Therapeutics. Peter Classi is an employee and minor shareholder in United Therapeutics Corporation. Eric Shen is an employee of United Therapeutics Corporation. Scott Manaker is a Grand Rounds speaker, lecturer, consultant, and expert witness on documentation, coding, billing, and reimbursement to hospitals, physicians, departments, practice groups, professional societies, insurers, and attorneys (defense, plaintiff "qui tam", US Attorneys General, and the Office of the Inspector General). Consultant to Apnicure, Aetna, Pfizer, Novartis and Johnson & Johnson. Expert witness in workers' compensation and in medical negligence matters. Chair, Practice Expense Subcommittee of the American Medical Association/Specialty Society Relative Value Update Committee (RUC). Member, Hospital Outpatient Panel, a federal advisory commission to the Center for Medicare/Medicaid Services (CMS) for the Outpatient Hospital Prospective Payment System. Stock held in 3M; and (by spouse) in Pfizer, Johnson & Johnson. Director of ACCP Enterprises, a wholly owned for-profit subsidiary of ACCP. Section Editor (Critical Care), UpToDate. Associate Editor, CHEST Journal. Trustee, National Board for Respiratory Care. EDAT- 2019/11/14 06:00 MHDA- 2021/06/01 06:00 PMCR- 2019/11/13 CRDT- 2019/11/14 06:00 PHST- 2019/07/25 00:00 [received] PHST- 2019/10/29 00:00 [accepted] PHST- 2019/11/14 06:00 [pubmed] PHST- 2021/06/01 06:00 [medline] PHST- 2019/11/14 06:00 [entrez] PHST- 2019/11/13 00:00 [pmc-release] AID - 10.1007/s00408-019-00289-2 [pii] AID - 289 [pii] AID - 10.1007/s00408-019-00289-2 [doi] PST - ppublish SO - Lung. 2020 Feb;198(1):65-86. doi: 10.1007/s00408-019-00289-2. Epub 2019 Nov 13.