{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T02:11:55Z","timestamp":1782180715308,"version":"3.54.5"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":1015,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["R-172-003-219-511"],"award-info":[{"award-number":["R-172-003-219-511"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A*STAR-NZ HRC","award":["JGC 10_027"],"award-info":[{"award-number":["JGC 10_027"]}]},{"name":"Clinician Scientist Award"},{"name":"New Zealand Heart Foundation Project Grant"},{"name":"TM Hosking Trust"},{"DOI":"10.13039\/501100001529","name":"Waikato Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001529","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HRC Programme Grant"},{"name":"New Zealand Heart Foundation Chair in Cardiovascular Studies"},{"name":"New Zealand Heart Foundation Chair of Heart Health"},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001529","name":"Waikato Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001529","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We investigated titration patterns of angiotensin-converting enzyme inhibitors (ACEis)\/angiotensin receptor blockers (ARBs) and beta-blockers, quality of life (QoL) over 6 months, and associated 1 year outcome [all-cause mortality\/heart failure (HF) hospitalization] in a real-world population with HF with reduced ejection fraction (HFrEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Participants with HFrEF (left ventricular ejection fraction &amp;lt;40%) from a prospective multi-centre study were examined for use and dose [relative to guideline-recommended maintenance dose (GRD)] of ACEis\/ARBs and beta-blockers at baseline and 6 months. \u2018Stay low\u2019 was defined as &amp;lt;50% GRD at both time points, \u2018stay high\u2019 as \u226550% GRD, and \u2018up-titrate\u2019 and \u2018down-titrate\u2019 as dose trajectories. Among 1110 patients (mean age 63 \u00b1 13 years, 16% women, 26% New York Heart Association Class III\/IV), 714 (64%) were multi-ethnic Asians from Singapore and 396 were from New Zealand (mainly European ethnicity). Baseline use of either ACEis\/ARBs or beta-blockers was high (87%). Loop diuretic was prescribed in &amp;gt;80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in &amp;gt;90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving \u226550% GRD for ACEis\/ARBs or beta-blockers. At 6 months, a large majority remained in the \u2018stay low\u2019 category, one third remained in \u2018stay high\u2019, whereas 10\u201316% up-titrated and 4\u20136% down-titrated. Patients with lower (vs. higher) N-terminal pro-beta-type natriuretic peptide levels were more likely to be up-titrated or be in \u2018stay high\u2019 for ACEis\/ARBs and beta-blockers (P = 0.002). Ischaemic aetiology, prior HF hospitalization, and enrolment in Singapore (vs. New Zealand) were independently associated with higher odds of \u2018staying low\u2019 (all P &amp;lt; 0.005) for prescribed doses of ACEis\/ARBs and beta-blockers. Adjusted for inverse probability weighting, \u2265100% GRD for ACEis\/ARBs [hazard ratio (HR) = 0.42; 95% confidence interval (CI) 0.24\u20130.73] and \u226550% GRD for beta-blockers (HR = 0.58; 95% CI 0.37\u20130.90) (vs. Nil) were associated with lower hazards for 1 year composite outcome. Country of enrolment did not modify the associations of dose categories with 1 year composite outcome. Higher medication doses were associated with greater improvements in QoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although HF medication use at baseline was high, most patients did not have these medications up-titrated over 6 months. Multiple clinical factors were associated with changes in medication dosages. Further research is urgently needed to investigate the causes of lack of up-titration of HF therapy (and its frequency), which could inform strategies for timely up-titration of HF therapy based on clinical and biochemical parameters.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14275","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:00:26Z","timestamp":1675227626000},"page":"1280-1293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Titration of Medications and Outcomes in Multi-Ethnic Heart Failure Cohorts (with Reduced Ejection Fraction) from Singapore and New Zealand"],"prefix":"10.1093","volume":"10","author":[{"given":"Tiew-Hwa Katherine","family":"Teng","sequence":"first","affiliation":[{"name":"National Heart Centre Singapore \u00a0","place":["Singapore"]},{"name":"Duke-NUS Medical School \u00a0","place":["Singapore"]},{"name":"School of Allied Health, University of Western Australia , Perth ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Ting","family":"Tay","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Ouwerkerk","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore \u00a0","place":["Singapore"]},{"name":"Department of Dermatology, Amsterdam Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Tromp","sequence":"additional","affiliation":[{"name":"Duke-NUS Medical School \u00a0","place":["Singapore"]},{"name":"Saw Swee Hock School of Public Health, National University of Singapore \u00a0","place":["Singapore"]},{"name":"Department of Cardiology, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"National University Heart Centre \u00a0","place":["Singapore"]},{"name":"Department of Medicine, University of Otago , Dunedin ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Gamble","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Auckland , Auckland ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Greene","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Duke University School of Medicine , Durham, NC ,","place":["USA"]},{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Hang","family":"Yiu","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, The University of Hong Kong Shenzhen Hospital , Shenzhen 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