Long-term Efficacies of Selective Vasodilators in Pulmonary Arterial Hypertension: a Comprehensive Comparison Using a Spontaneous Reporting Database

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2024 Jan 5

PMID 38180559

Authors

Koji Suzuki

Tatsuya Yagi

Junichi Kawakami

Affiliations

Soon will be listed here.

Abstract

There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to the small population and lack of information on death in Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Of 1969 PAH patients reported in the JADER database, 1208 were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR, 0.38; 95% confidence interval (CI), 0.23-0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially among the macitentan users (aHR, 0.30; 95% CI, 0.22-0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR, 1.56; 95% CI, 1.19-2.04). Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH.

References

Barst R, Rubin L, Long W, McGoon M, Rich S, Badesch D . A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996; 334(5):296-301. DOI: 10.1056/NEJM199602013340504. View

Barst R, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L . Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2003; 41(12):2119-25. DOI: 10.1016/s0735-1097(03)00463-7. View

Bourge R, Waxman A, Gomberg-Maitland M, Shapiro S, Tarver 3rd J, Zwicke D . Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial. Chest. 2016; 150(1):27-34. DOI: 10.1016/j.chest.2015.11.005. View

Chaumais M, Jobard M, Huertas A, Vignand-Courtin C, Humbert M, Sitbon O . Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010; 6(12):1587-98. DOI: 10.1517/17425255.2010.534458. View

Galie N, Olschewski H, Oudiz R, Torres F, Frost A, Ghofrani H . Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation. 2008; 117(23):3010-9. DOI: 10.1161/CIRCULATIONAHA.107.742510. View

Galie N, Barbera J, Frost A, Ghofrani H, Hoeper M, McLaughlin V . Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015; 373(9):834-44. DOI: 10.1056/NEJMoa1413687. View

Hiramatsu K, Barrett A, Miyata Y . Current Status, Challenges, and Future Perspectives of Real-World Data and Real-World Evidence in Japan. Drugs Real World Outcomes. 2021; 8(4):459-480. PMC: 8605941. DOI: 10.1007/s40801-021-00266-3. View

Hoeper M, Al-Hiti H, Benza R, Chang S, Corris P, Gibbs J . Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2021; 9(6):573-584. DOI: 10.1016/S2213-2600(20)30532-4. View

Hoeper M, Pausch C, Grunig E, Staehler G, Huscher D, Pittrow D . Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry. Eur Respir J. 2021; 59(6). PMC: 9160392. DOI: 10.1183/13993003.02024-2021. View

10.

Humbert M, Segal E, Kiely D, Carlsen J, Schwierin B, Hoeper M . Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007; 30(2):338-44. DOI: 10.1183/09031936.00138706. View

11.

Humbert M, Kovacs G, Hoeper M, Badagliacca R, Berger R, Brida M . 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2022; 61(1). DOI: 10.1183/13993003.00879-2022. View

12.

Kloner R, Hutter A, Emmick J, Mitchell M, Denne J, Jackson G . Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol. 2003; 42(10):1855-60. DOI: 10.1016/j.jacc.2003.09.023. View

13.

Lau E, Giannoulatou E, Celermajer D, Humbert M . Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017; 14(10):603-614. DOI: 10.1038/nrcardio.2017.84. View

14.

Leber L, Beaudet A, Muller A . Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review. Pulm Circ. 2021; 11(1):2045894020977300. PMC: 7797595. DOI: 10.1177/2045894020977300. View

15.

Liu J, Barrett J, Leonardi E, Lee L, Roychoudhury S, Chen Y . Natural History and Real-World Data in Rare Diseases: Applications, Limitations, and Future Perspectives. J Clin Pharmacol. 2022; 62 Suppl 2:S38-S55. PMC: 10107901. DOI: 10.1002/jcph.2134. View

16.

McLaughlin V, Shillington A, Rich S . Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106(12):1477-82. DOI: 10.1161/01.cir.0000029100.82385.58. View

17.

Ogawa A, Ejiri K, Matsubara H . Long-term patient survival with idiopathic/heritable pulmonary arterial hypertension treated at a single center in Japan. Life Sci. 2014; 118(2):414-9. DOI: 10.1016/j.lfs.2014.01.077. View

18.

Ogawa A, Satoh T, Tamura Y, Fukuda K, Matsubara H . Survival of Japanese Patients With Idiopathic/Heritable Pulmonary Arterial Hypertension. Am J Cardiol. 2017; 119(9):1479-1484. DOI: 10.1016/j.amjcard.2017.01.015. View

19.

Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin L . Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002; 347(5):322-9. DOI: 10.1056/NEJMoa020204. View

20.

Pitre T, Su J, Cui S, Scanlan R, Chiang C, Husnudinov R . Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis. Eur Respir Rev. 2022; 31(165). PMC: 9724821. DOI: 10.1183/16000617.0036-2022. View