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      Current status of pulmonary arterial hypertension in Korea

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          Abstract

          Pulmonary arterial hypertension (PAH) is characterized by remodeling of the distal pulmonary arteries resulting in high pulmonary vascular resistance and, eventually, right ventricular heart failure. Although current advances in PAH therapy have improved outcomes, poor survival remains a reality worldwide, including Korea. One of the most important issues in PAH is the late diagnosis, since screening or diagnostic efforts are often overlooked due to the rarity of disease. Data from Korean registries and observational cohorts show that delayed detection leads to increased morbidity. Additionally, low percentages of Korean patients are committed to intensive PAH-targeted therapy. Current Korean health insurance policies’ lack of coverage for new PAH-targeted drugs and upfront combination therapy may also hamper the improvement of treatment outcomes. Understanding individual variability in response to therapeutics through deep phenotyping is a novel strategy that should be considered when treating PAH. Overall, early detection of PAH by proactive screening together with early, intensive, individualized PAH therapy using deep phenotyping is crucial for improving prognoses for PAH patients in Korea.

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          Most cited references59

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          Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.

          Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.
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            Selexipag for the Treatment of Pulmonary Arterial Hypertension.

            In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension.
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              Tadalafil therapy for pulmonary arterial hypertension.

              Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway. In this 16-week, double-blind, placebo-controlled study, 405 patients with pulmonary arterial hypertension (idiopathic or associated), either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan, were randomized to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes. Changes in World Health Organization functional class, clinical worsening, and health-related quality of life were also assessed. Patients completing the 16-week study could enter a long-term extension study. Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner; only the 40-mg dose met the prespecified level of statistical significance (P<0.01). Overall, the mean placebo-corrected treatment effect was 33 m (95% confidence interval, 15 to 50 m). In the bosentan-naive group, the treatment effect was 44 m (95% confidence interval, 20 to 69 m) compared with 23 m (95% confidence interval, -2 to 48 m) in patients on background bosentan therapy. Tadalafil 40 mg improved the time to clinical worsening (P=0.041), incidence of clinical worsening (68% relative risk reduction; P=0.038), and health-related quality of life. The changes in World Health Organization functional class were not statistically significant. The most common treatment-related adverse events reported with tadalafil were headache, myalgia, and flushing. In patients with pulmonary arterial hypertension, tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening.
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                Author and article information

                Journal
                Korean J Intern Med
                Korean J. Intern. Med
                KJIM
                The Korean Journal of Internal Medicine
                The Korean Association of Internal Medicine
                1226-3303
                2005-6648
                July 2019
                1 July 2019
                : 34
                : 4
                : 696-707
                Affiliations
                [1 ]Gachon Cardiovascular Research Institute, Gachon University, Incheon, Korea
                [2 ]Department of Cardiovascular Medicine, Gachon University Gil Medical Center, Incheon, Korea
                Author notes
                Correspondence to Wook-Jin Chung, M.D. Department of Cardiovascular Medicine, Gachon University College of Medicine, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea Tel: +82-32-460-3663 Fax: +82-32-469-1906 E-mail: heart@ 123456gachon.ac.kr

                This paper was contributed by The Korean Society of Hypertension.

                Author information
                http://orcid.org/0000-0002-9767-7098
                Article
                kjim-2019-185
                10.3904/kjim.2019.185
                6610200
                31272141
                af15cef8-f907-4c39-8980-b30228384133
                Copyright © 2019 The Korean Association of Internal Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 June 2019
                : 14 June 2019
                Categories
                Review

                Internal medicine
                pulmonary arterial hypertension,early diagnosis,pharmacotherapy,phenotyping,precision medicine

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