Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study

Maeda, Makiko; Humber, Douglas; Hida, Eisuke; Ohtani, Tomohito; Wang, Guannan; Wu, Tong; Takeda, Shiori; Situ, Jacinta N.; Hayashi, Jun; Nonen, Shinpei; Takeda, Toshihiro; Okamoto, Hiroshi; Hori, Masatsugu; Sakata, Yasushi; Fujio, Yasushi; Tsunoda, Shirley M.

doi:https://doi.org/10.1371/journal.pone.0299510

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study

Maeda, Makiko; Humber, Douglas; Hida, Eisuke et al.

PLoS ONE, 2024, 19(3.0), e0299510

Number of Access:104（2025-04-30 13:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95643

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Title	Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study
Creator	NRID 1000070461168 1000070461168 researchmap permalink read0091695 read0091695 Scopus Author ID 7404013283 7404013283 CreatorName Maeda, Makiko
	CreatorName Humber, Douglas
	NRID 1000030469952 1000030469952 ORCID 0000-0001-9381-2013 0000-0001-9381-2013 researchmap permalink ehida ehida Scopus Author ID 57190171039 57190171039 CreatorName Hida, Eisuke
	NRID 1000030623897 1000030623897 researchmap permalink tohtani tohtani Scopus Author ID 57932819800 57932819800 CreatorName Ohtani, Tomohito
	CreatorName Wang, Guannan
	CreatorName Wu, Tong
	CreatorName Takeda, Shiori
	CreatorName Situ, Jacinta N.
	CreatorName Hayashi, Jun
	NRID 1000040467527 1000040467527 CreatorName Nonen, Shinpei
	NRID 1000070506493 1000070506493 researchmap permalink ttakeda_research ttakeda_research Scopus Author ID 7403572788 7403572788 CreatorName Takeda, Toshihiro
	CreatorName Okamoto, Hiroshi
	NRID 1000020124779 1000020124779 researchmap permalink read0013662 read0013662 CreatorName Hori, Masatsugu
	NRID 1000000397671 1000000397671 ORCID 0000-0002-5618-4721 0000-0002-5618-4721 researchmap permalink C4589 C4589 Scopus Author ID 35395964700 35395964700 CreatorName Sakata, Yasushi
	NRID 1000020359839 1000020359839 ORCID 0000-0003-0828-2930 0000-0003-0828-2930 researchmap permalink yfujio yfujio Scopus Author ID 7006517527 7006517527 CreatorName Fujio, Yasushi
	CreatorName Tsunoda, Shirley M.
Description	Maeda M., Humber D., Hida E., et al. (2024) Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study. PLoS ONE 19(3.0): e0299510. doi.org/10.1371/journal.pone.0299510.
Abstract	The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
Publisher	Public Library of Science
Source Title	PLoS ONE
Volume (Issue)	19(3.0)
Page	e0299510
Date of Issued	2024-03-07
Language	English
Handle URL	https://hdl.handle.net/11094/95643
eISSN	19326203
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1371/journal.pone.0299510
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	PLoS ONE. 2024, 19(3.0), p. e0299510
DC.title	Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study
DC.creator	Maeda, Makiko
	Humber, Douglas
	Hida, Eisuke
	Ohtani, Tomohito
	Wang, Guannan
	Wu, Tong
	Takeda, Shiori
	Situ, Jacinta N.
	Hayashi, Jun
	Nonen, Shinpei
	Takeda, Toshihiro
	Okamoto, Hiroshi
	Hori, Masatsugu
	Sakata, Yasushi
	Fujio, Yasushi
	Tsunoda, Shirley M.
DC.publisher	Public Library of Science
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-03-07
DC.identifier	https://doi.org/10.1371/journal.pone.0299510
DC.description	Maeda M., Humber D., Hida E., et al. (2024) Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study. PLoS ONE 19(3.0): e0299510. doi.org/10.1371/journal.pone.0299510.
DCTERMS.abstract	The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	95643
citation_title	Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study
citation_author	Maeda, Makiko
	Humber, Douglas
	Hida, Eisuke
	Ohtani, Tomohito
	Wang, Guannan
	Wu, Tong
	Takeda, Shiori
	Situ, Jacinta N.
	Hayashi, Jun
	Nonen, Shinpei
	Takeda, Toshihiro
	Okamoto, Hiroshi
	Hori, Masatsugu
	Sakata, Yasushi
	Fujio, Yasushi
	Tsunoda, Shirley M.
citation_publisher	Public Library of Science
citation_language	English
citation_date	2024-03-07
citation_journal_title	PLoS ONE
citation_volume	19
citation_issue	3.0
citation_firstpage	e0299510
citation_doi	https://doi.org/10.1371/journal.pone.0299510
citation_public_url	https://hdl.handle.net/11094/95643

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study

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