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Title: Titration of medications and outcomes in multi-ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand
Authors: Teng, Tiew-Hwa Katherine 
Tay, Wan Ting
Ouwerkerk, Wouter
Tromp, Jasper 
Richards, A Mark 
Gamble, Greg
Greene, Stephen J
Yiu, Kai-Hang
Poppe, Katrina
Ling, Lieng Hsi 
Lund, Mayanna
Sim, David 
Devlin, Gerard
Loh, Seet Yoong
Troughton, Richard
Ren, Qing-wen
Jaufeerally, Fazlur 
Lee, Shao Guang Sheldon 
Tan, Ru San 
Soon, Dinna Kar Nee
Leong, Gerald
Ong, Hean Yee 
Yeo, Daniel PS 
Lam, Carolyn SP 
Doughty, Rob N
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Medication dose
Heart failure
Reduced ejection fraction
Renin-angiotensin system inhibitors
Issue Date: 1-Apr-2023
Citation: Teng, Tiew-Hwa Katherine, Tay, Wan Ting, Ouwerkerk, Wouter, Tromp, Jasper, Richards, A Mark, Gamble, Greg, Greene, Stephen J, Yiu, Kai-Hang, Poppe, Katrina, Ling, Lieng Hsi, Lund, Mayanna, Sim, David, Devlin, Gerard, Loh, Seet Yoong, Troughton, Richard, Ren, Qing-wen, Jaufeerally, Fazlur, Lee, Shao Guang Sheldon, Tan, Ru San, Soon, Dinna Kar Nee, Leong, Gerald, Ong, Hean Yee, Yeo, Daniel PS, Lam, Carolyn SP, Doughty, Rob N (2023-04-01). Titration of medications and outcomes in multi-ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand. ESC HEART FAILURE 10 (2). ScholarBank@NUS Repository.
Abstract: Aims: 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). Methods and results: Participants with HFrEF (left ventricular ejection fraction <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. ‘Stay low’ was defined as <50% GRD at both time points, ‘stay high’ as ≥50% GRD, and ‘up-titrate’ and ‘down-titrate’ as dose trajectories. Among 1110 patients (mean age 63 ± 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 >80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in >90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving ≥50% GRD for ACEis/ARBs or beta-blockers. At 6 months, a large majority remained in the ‘stay low’ category, one third remained in ‘stay high’, whereas 10–16% up-titrated and 4–6% 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 ‘stay high’ 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 ‘staying low’ (all P < 0.005) for prescribed doses of ACEis/ARBs and beta-blockers. Adjusted for inverse probability weighting, ≥100% GRD for ACEis/ARBs [hazard ratio (HR) = 0.42; 95% confidence interval (CI) 0.24–0.73] and ≥50% GRD for beta-blockers (HR = 0.58; 95% CI 0.37–0.90) (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. Conclusions: 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.
ISSN: 2055-5822
DOI: 10.1002/ehf2.14275
Appears in Collections:Staff Publications

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