Changes in the Characteristics and Initial Treatments of Pulmonary Hypertension Between 2008 and 2020 in Japan

Yuichi Tamura; Hiraku Kumamaru; Takumi Inami; Hiromi Matsubara; Ken-Ichi Hirata; Ichizo Tsujino; Rika Suda; Hiroaki Miyata; Shiori Nishimura; Byron Sigel; Masashi Takano; Koichiro Tatsumi; Japan Pulmonary Hypertension Registry (JAPHR) Network

doi:10.1016/j.jacasi.2022.02.011

Changes in the Characteristics and Initial Treatments of Pulmonary Hypertension Between 2008 and 2020 in Japan

JACC Asia. 2022 May 17;2(3):273-284. doi: 10.1016/j.jacasi.2022.02.011. eCollection 2022 Jun.

Affiliations

¹ Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
² Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Cardiovascular Medicine, Kyorin University Hospital, Tokyo, Japan.
⁴ Department of Clinical Science, National Hospital Organization Okayama Medical Center, Okayama, Japan.
⁵ Division of Cardiovascular Medicine Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
⁶ First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
⁷ Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
⁸ Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan.
⁹ Medical Affairs, Janssen Pharmaceutical K.K., Tokyo, Japan.

Abstract

Background: Pulmonary arterial hypertension (PAH) is a rare, progressive disease. The treatment landscape for PAH in Japan has evolved considerably in recent years, but there is limited knowledge of the changes in treatment practices or patient characteristics.

Objectives: The aim of this study was to evaluate the changes in characteristics and initial treatments for PAH in Japan over time.

Methods: This study used data from the Japan Pulmonary Hypertension Registry (JAPHR) to compare patient characteristics and treatment practices between 2008-2015 (n = 316) and 2016-2020 (n = 315).

Results: The mean ± standard deviation age at diagnosis increased from 47.9 ± 16.7 years in 2008-2015 to 52.7 ± 16.9 years in 2016-2020. The mean pulmonary arterial pressure decreased from 45.4 ± 15.0 to 38.6 ± 13.1 mm Hg. Idiopathic/hereditary PAH was the most common etiology in both periods (50.0% and 51.1%, respectively). The proportion of patients prescribed oral/inhaled combination therapies increased from 47.8% to 57.5%. Oral/inhaled combination therapies were frequently prescribed to patients with congenital heart disease-related PAH (81.8%). There was no significant trend in prescribing practices based on French low-risk criteria: among patients with 0, 1, 2, 3, or 4 criteria, 53.8%, 68.8%, 52.8%, 66.7%, and 39.4% were prescribed oral/inhaled combination therapies, and 0%, 16.7%, 27.0%, 17.3%, and 15.2% were prescribed oral/inhaled monotherapies. Macitentan, tadalafil, selexipag, and epoprostenol were the most frequently prescribed drugs.

Conclusions: The severity of PAH decreased over time in Japan. Oral/inhaled combination therapies were generally preferred. Physicians generally prescribed therapies after considering the patients' hemodynamics and clinical severity. (Japan Pulmonary Hypertension Registry [JAPHR]; UMIN000026680).

Keywords: 6MWD, 6-minute walk distance; AMED, Agency for Medical Research and Development; BNP, brain natriuretic peptide; CHD-PAH, congenital heart disease–related pulmonary arterial hypertension; CTD-PAH, connective tissue disease–related pulmonary arterial hypertension; ERA, endothelin receptor antagonist; HPAH, hereditary pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; JAPHR, Japan Pulmonary Hypertension Registry; Japan; NO, nitric oxide; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PGI2, prostacyclin; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; PoPH, portopulmonary hypertension; mPAP, mean pulmonary arterial pressure; mRAP, mean right arterial pressure; pulmonary arterial hypertension; risk criteria; treatment.