Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries
Background Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many par...
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| Veröffentlicht in: | European journal of heart failure 2020-08, Vol.22 (8), p.1472-1482 |
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| creator | Ouwerkerk, Wouter Teng, Tiew‐Hwa K. Tromp, Jasper Tay, Wan Ting Cleland, John G. Veldhuisen, Dirk J. Dickstein, Kenneth Ng, Leong L. Lang, Chim C. Anker, Stefan D. Zannad, Faiez Hung, Chung‐Lieh Sawhney, Jitendra P.S. Naik, Ajay Shimizu, Wataru Hagiwara, Nobuhisa Wander, Gurpreet Singh Anand, Inder Richards, A. Mark Voors, Adriaan A. Lam, Carolyn S.P. |
| description | Background
Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up‐titration of ACEi/ARBs and β‐blockers with all‐cause mortality and its combination with hospitalization for HF.
Methods and results
A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT‐CHF; n = 2100) and Asian (ASIAN‐HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline‐recommended target doses (GRTD) of combination ACEi/ARB and β‐blocker therapy, adjusted for
indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β‐blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β‐blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26–0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up‐titrating β‐blockers was associated with a consistent and greater reduction in hazards of all‐cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25–0.63) than corresponding ACEi/ARB up‐titration (HR 0.75, 95% CI 0.53–1.07).
Conclusion
This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β‐blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up‐titrating β‐blockers to target dose was associated with greater mortality reduction than up‐titrating ACEi/ARB. |
| doi_str_mv | 10.1002/ejhf.1869 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03719991v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2417400914</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3099-33c477cfa3d9dcc581a2e38376fc7c3e6c4ea53521e4af31e1782185d50479a53</originalsourceid><addsrcrecordid>eNp1kcFy0zAQhj0MDC2FAy_A6AgHt5JlxxI3N5M0YTL00HD2yPIqVrClIsl0cusjMNN34wH6JChJKSdO2l19-_878yfJe4LPCcbZBWw7dU7YhL9ITgkreYpZnr-MNWUs5SzPTpI33m8xJmXEXycnNCsY5Vl2mvyeKQUyeGQVknZotIEWOTDaPN4_CLPRNoDxx65vrQ_grAHkd7EakDadbnSwDgnTogaCeLz_1fRWfgeHggMRBjABWYPsGKI8-LiCOhAuICV0PzpAdzp00bEdZXSGbTxGR145cSg-xwWvN128UDk7oMvl9c26Wkeb6WJ-cK1ultXX2MfWwUb74DT4t8krJXoP757es-TbfLaeLtLV9dVyWq1SSTHnKaUyL0upBG15K2XBiMiAMlpOlCwlhYnMQRS0yAjkQlECpGQZYUVb4Lzk8ecs-XTU7URf3zo9CLerrdD1olrV-xmmJeGck58ksh-P7K2zP0bwoR60l9D3woAdfZ3lpMwx5iT_Jyud9d6BetYmuN5HXu8jr_eRR_bDk-zYDNA-k38zjsDFEbjTPez-r1TPvizmB8k_97W-Xw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417400914</pqid></control><display><type>article</type><title>Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><creator>Ouwerkerk, Wouter ; Teng, Tiew‐Hwa K. ; Tromp, Jasper ; Tay, Wan Ting ; Cleland, John G. ; Veldhuisen, Dirk J. ; Dickstein, Kenneth ; Ng, Leong L. ; Lang, Chim C. ; Anker, Stefan D. ; Zannad, Faiez ; Hung, Chung‐Lieh ; Sawhney, Jitendra P.S. ; Naik, Ajay ; Shimizu, Wataru ; Hagiwara, Nobuhisa ; Wander, Gurpreet Singh ; Anand, Inder ; Richards, A. Mark ; Voors, Adriaan A. ; Lam, Carolyn S.P.</creator><creatorcontrib>Ouwerkerk, Wouter ; Teng, Tiew‐Hwa K. ; Tromp, Jasper ; Tay, Wan Ting ; Cleland, John G. ; Veldhuisen, Dirk J. ; Dickstein, Kenneth ; Ng, Leong L. ; Lang, Chim C. ; Anker, Stefan D. ; Zannad, Faiez ; Hung, Chung‐Lieh ; Sawhney, Jitendra P.S. ; Naik, Ajay ; Shimizu, Wataru ; Hagiwara, Nobuhisa ; Wander, Gurpreet Singh ; Anand, Inder ; Richards, A. Mark ; Voors, Adriaan A. ; Lam, Carolyn S.P.</creatorcontrib><description>Background
Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up‐titration of ACEi/ARBs and β‐blockers with all‐cause mortality and its combination with hospitalization for HF.
Methods and results
A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT‐CHF; n = 2100) and Asian (ASIAN‐HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline‐recommended target doses (GRTD) of combination ACEi/ARB and β‐blocker therapy, adjusted for
indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β‐blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β‐blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26–0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up‐titrating β‐blockers was associated with a consistent and greater reduction in hazards of all‐cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25–0.63) than corresponding ACEi/ARB up‐titration (HR 0.75, 95% CI 0.53–1.07).
Conclusion
This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β‐blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up‐titrating β‐blockers to target dose was associated with greater mortality reduction than up‐titrating ACEi/ARB.</description><identifier>ISSN: 1388-9842</identifier><identifier>EISSN: 1879-0844</identifier><identifier>DOI: 10.1002/ejhf.1869</identifier><identifier>PMID: 32583922</identifier><language>eng</language><publisher>Oxford, UK: John Wiley & Sons, Ltd</publisher><subject>Aged ; Aldosterone ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Asia - epidemiology ; Cardiology and cardiovascular system ; Europe ; Evidence‐based pharmacotherapy ; Female ; Heart failure ; Heart Failure - drug therapy ; Heart Failure - epidemiology ; Human health and pathology ; Humans ; Life Sciences ; Male ; Middle Aged ; Outcomes ; Prospective Studies ; Reduced ejection fraction ; Registries ; Renin-Angiotensin System ; Stroke Volume ; Up‐titration ; Ventricular Function, Left</subject><ispartof>European journal of heart failure, 2020-08, Vol.22 (8), p.1472-1482</ispartof><rights>2020 European Society of Cardiology</rights><rights>2020 European Society of Cardiology.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3099-33c477cfa3d9dcc581a2e38376fc7c3e6c4ea53521e4af31e1782185d50479a53</citedby><cites>FETCH-LOGICAL-c3099-33c477cfa3d9dcc581a2e38376fc7c3e6c4ea53521e4af31e1782185d50479a53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fejhf.1869$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fejhf.1869$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32583922$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.univ-lorraine.fr/hal-03719991$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ouwerkerk, Wouter</creatorcontrib><creatorcontrib>Teng, Tiew‐Hwa K.</creatorcontrib><creatorcontrib>Tromp, Jasper</creatorcontrib><creatorcontrib>Tay, Wan Ting</creatorcontrib><creatorcontrib>Cleland, John G.</creatorcontrib><creatorcontrib>Veldhuisen, Dirk J.</creatorcontrib><creatorcontrib>Dickstein, Kenneth</creatorcontrib><creatorcontrib>Ng, Leong L.</creatorcontrib><creatorcontrib>Lang, Chim C.</creatorcontrib><creatorcontrib>Anker, Stefan D.</creatorcontrib><creatorcontrib>Zannad, Faiez</creatorcontrib><creatorcontrib>Hung, Chung‐Lieh</creatorcontrib><creatorcontrib>Sawhney, Jitendra P.S.</creatorcontrib><creatorcontrib>Naik, Ajay</creatorcontrib><creatorcontrib>Shimizu, Wataru</creatorcontrib><creatorcontrib>Hagiwara, Nobuhisa</creatorcontrib><creatorcontrib>Wander, Gurpreet Singh</creatorcontrib><creatorcontrib>Anand, Inder</creatorcontrib><creatorcontrib>Richards, A. Mark</creatorcontrib><creatorcontrib>Voors, Adriaan A.</creatorcontrib><creatorcontrib>Lam, Carolyn S.P.</creatorcontrib><title>Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries</title><title>European journal of heart failure</title><addtitle>Eur J Heart Fail</addtitle><description>Background
Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up‐titration of ACEi/ARBs and β‐blockers with all‐cause mortality and its combination with hospitalization for HF.
Methods and results
A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT‐CHF; n = 2100) and Asian (ASIAN‐HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline‐recommended target doses (GRTD) of combination ACEi/ARB and β‐blocker therapy, adjusted for
indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β‐blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β‐blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26–0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up‐titrating β‐blockers was associated with a consistent and greater reduction in hazards of all‐cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25–0.63) than corresponding ACEi/ARB up‐titration (HR 0.75, 95% CI 0.53–1.07).
Conclusion
This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β‐blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up‐titrating β‐blockers to target dose was associated with greater mortality reduction than up‐titrating ACEi/ARB.</description><subject>Aged</subject><subject>Aldosterone</subject><subject>Angiotensin Receptor Antagonists</subject><subject>Angiotensin-Converting Enzyme Inhibitors</subject><subject>Asia - epidemiology</subject><subject>Cardiology and cardiovascular system</subject><subject>Europe</subject><subject>Evidence‐based pharmacotherapy</subject><subject>Female</subject><subject>Heart failure</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - epidemiology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Outcomes</subject><subject>Prospective Studies</subject><subject>Reduced ejection fraction</subject><subject>Registries</subject><subject>Renin-Angiotensin System</subject><subject>Stroke Volume</subject><subject>Up‐titration</subject><subject>Ventricular Function, Left</subject><issn>1388-9842</issn><issn>1879-0844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFy0zAQhj0MDC2FAy_A6AgHt5JlxxI3N5M0YTL00HD2yPIqVrClIsl0cusjMNN34wH6JChJKSdO2l19-_878yfJe4LPCcbZBWw7dU7YhL9ITgkreYpZnr-MNWUs5SzPTpI33m8xJmXEXycnNCsY5Vl2mvyeKQUyeGQVknZotIEWOTDaPN4_CLPRNoDxx65vrQ_grAHkd7EakDadbnSwDgnTogaCeLz_1fRWfgeHggMRBjABWYPsGKI8-LiCOhAuICV0PzpAdzp00bEdZXSGbTxGR145cSg-xwWvN128UDk7oMvl9c26Wkeb6WJ-cK1ultXX2MfWwUb74DT4t8krJXoP757es-TbfLaeLtLV9dVyWq1SSTHnKaUyL0upBG15K2XBiMiAMlpOlCwlhYnMQRS0yAjkQlECpGQZYUVb4Lzk8ecs-XTU7URf3zo9CLerrdD1olrV-xmmJeGck58ksh-P7K2zP0bwoR60l9D3woAdfZ3lpMwx5iT_Jyud9d6BetYmuN5HXu8jr_eRR_bDk-zYDNA-k38zjsDFEbjTPez-r1TPvizmB8k_97W-Xw</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Ouwerkerk, Wouter</creator><creator>Teng, Tiew‐Hwa K.</creator><creator>Tromp, Jasper</creator><creator>Tay, Wan Ting</creator><creator>Cleland, John G.</creator><creator>Veldhuisen, Dirk J.</creator><creator>Dickstein, Kenneth</creator><creator>Ng, Leong L.</creator><creator>Lang, Chim C.</creator><creator>Anker, Stefan D.</creator><creator>Zannad, Faiez</creator><creator>Hung, Chung‐Lieh</creator><creator>Sawhney, Jitendra P.S.</creator><creator>Naik, Ajay</creator><creator>Shimizu, Wataru</creator><creator>Hagiwara, Nobuhisa</creator><creator>Wander, Gurpreet Singh</creator><creator>Anand, Inder</creator><creator>Richards, A. Mark</creator><creator>Voors, Adriaan A.</creator><creator>Lam, Carolyn S.P.</creator><general>John Wiley & Sons, Ltd</general><general>European Society of Cardiology (Wiley)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>202008</creationdate><title>Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries</title><author>Ouwerkerk, Wouter ; Teng, Tiew‐Hwa K. ; Tromp, Jasper ; Tay, Wan Ting ; Cleland, John G. ; Veldhuisen, Dirk J. ; Dickstein, Kenneth ; Ng, Leong L. ; Lang, Chim C. ; Anker, Stefan D. ; Zannad, Faiez ; Hung, Chung‐Lieh ; Sawhney, Jitendra P.S. ; Naik, Ajay ; Shimizu, Wataru ; Hagiwara, Nobuhisa ; Wander, Gurpreet Singh ; Anand, Inder ; Richards, A. Mark ; Voors, Adriaan A. ; Lam, Carolyn S.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3099-33c477cfa3d9dcc581a2e38376fc7c3e6c4ea53521e4af31e1782185d50479a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Aldosterone</topic><topic>Angiotensin Receptor Antagonists</topic><topic>Angiotensin-Converting Enzyme Inhibitors</topic><topic>Asia - epidemiology</topic><topic>Cardiology and cardiovascular system</topic><topic>Europe</topic><topic>Evidence‐based pharmacotherapy</topic><topic>Female</topic><topic>Heart failure</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - epidemiology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Outcomes</topic><topic>Prospective Studies</topic><topic>Reduced ejection fraction</topic><topic>Registries</topic><topic>Renin-Angiotensin System</topic><topic>Stroke Volume</topic><topic>Up‐titration</topic><topic>Ventricular Function, Left</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ouwerkerk, Wouter</creatorcontrib><creatorcontrib>Teng, Tiew‐Hwa K.</creatorcontrib><creatorcontrib>Tromp, Jasper</creatorcontrib><creatorcontrib>Tay, Wan Ting</creatorcontrib><creatorcontrib>Cleland, John G.</creatorcontrib><creatorcontrib>Veldhuisen, Dirk J.</creatorcontrib><creatorcontrib>Dickstein, Kenneth</creatorcontrib><creatorcontrib>Ng, Leong L.</creatorcontrib><creatorcontrib>Lang, Chim C.</creatorcontrib><creatorcontrib>Anker, Stefan D.</creatorcontrib><creatorcontrib>Zannad, Faiez</creatorcontrib><creatorcontrib>Hung, Chung‐Lieh</creatorcontrib><creatorcontrib>Sawhney, Jitendra P.S.</creatorcontrib><creatorcontrib>Naik, Ajay</creatorcontrib><creatorcontrib>Shimizu, Wataru</creatorcontrib><creatorcontrib>Hagiwara, Nobuhisa</creatorcontrib><creatorcontrib>Wander, Gurpreet Singh</creatorcontrib><creatorcontrib>Anand, Inder</creatorcontrib><creatorcontrib>Richards, A. Mark</creatorcontrib><creatorcontrib>Voors, Adriaan A.</creatorcontrib><creatorcontrib>Lam, Carolyn S.P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>European journal of heart failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ouwerkerk, Wouter</au><au>Teng, Tiew‐Hwa K.</au><au>Tromp, Jasper</au><au>Tay, Wan Ting</au><au>Cleland, John G.</au><au>Veldhuisen, Dirk J.</au><au>Dickstein, Kenneth</au><au>Ng, Leong L.</au><au>Lang, Chim C.</au><au>Anker, Stefan D.</au><au>Zannad, Faiez</au><au>Hung, Chung‐Lieh</au><au>Sawhney, Jitendra P.S.</au><au>Naik, Ajay</au><au>Shimizu, Wataru</au><au>Hagiwara, Nobuhisa</au><au>Wander, Gurpreet Singh</au><au>Anand, Inder</au><au>Richards, A. Mark</au><au>Voors, Adriaan A.</au><au>Lam, Carolyn S.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries</atitle><jtitle>European journal of heart failure</jtitle><addtitle>Eur J Heart Fail</addtitle><date>2020-08</date><risdate>2020</risdate><volume>22</volume><issue>8</issue><spage>1472</spage><epage>1482</epage><pages>1472-1482</pages><issn>1388-9842</issn><eissn>1879-0844</eissn><abstract>Background
Angiotensin‐converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β‐blockers are guideline‐recommended first‐line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under‐dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up‐titration of ACEi/ARBs and β‐blockers with all‐cause mortality and its combination with hospitalization for HF.
Methods and results
A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT‐CHF; n = 2100) and Asian (ASIAN‐HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline‐recommended target doses (GRTD) of combination ACEi/ARB and β‐blocker therapy, adjusted for
indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β‐blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β‐blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26–0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up‐titrating β‐blockers was associated with a consistent and greater reduction in hazards of all‐cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25–0.63) than corresponding ACEi/ARB up‐titration (HR 0.75, 95% CI 0.53–1.07).
Conclusion
This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β‐blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up‐titrating β‐blockers to target dose was associated with greater mortality reduction than up‐titrating ACEi/ARB.</abstract><cop>Oxford, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>32583922</pmid><doi>10.1002/ejhf.1869</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1388-9842 |
| ispartof | European journal of heart failure, 2020-08, Vol.22 (8), p.1472-1482 |
| issn | 1388-9842 1879-0844 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_03719991v1 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content |
| subjects | Aged Aldosterone Angiotensin Receptor Antagonists Angiotensin-Converting Enzyme Inhibitors Asia - epidemiology Cardiology and cardiovascular system Europe Evidence‐based pharmacotherapy Female Heart failure Heart Failure - drug therapy Heart Failure - epidemiology Human health and pathology Humans Life Sciences Male Middle Aged Outcomes Prospective Studies Reduced ejection fraction Registries Renin-Angiotensin System Stroke Volume Up‐titration Ventricular Function, Left |
| title | Effects of combined renin–angiotensin–aldosterone system inhibitor and beta‐blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT‐CHF and ASIAN‐HF registries |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T19%3A56%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20combined%20renin%E2%80%93angiotensin%E2%80%93aldosterone%20system%20inhibitor%20and%20beta%E2%80%90blocker%20treatment%20on%20outcomes%20in%20heart%20failure%20with%20reduced%20ejection%20fraction:%20insights%20from%20BIOSTAT%E2%80%90CHF%20and%20ASIAN%E2%80%90HF%20registries&rft.jtitle=European%20journal%20of%20heart%20failure&rft.au=Ouwerkerk,%20Wouter&rft.date=2020-08&rft.volume=22&rft.issue=8&rft.spage=1472&rft.epage=1482&rft.pages=1472-1482&rft.issn=1388-9842&rft.eissn=1879-0844&rft_id=info:doi/10.1002/ejhf.1869&rft_dat=%3Cproquest_hal_p%3E2417400914%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2417400914&rft_id=info:pmid/32583922&rfr_iscdi=true |