Abstract：
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).
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.
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.
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.
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.
摘要：
目的：我们研究了血管紧张素转换酶抑制剂（ACEis）/血管紧张素受体阻滞剂（ARBs）和β受体阻滞剂的滴定模式，6个月以上的生活质量（QoL），和相关的1年结局[全因死亡率/心力衰竭（HF）住院]在现实世界的人口与HF降低射血分数（HFrEF）。
结果：一项前瞻性多中心研究的HFrEF（左心室射血分数<40％）参与者在基线和6个月时检查了ACEis/ARB和β受体阻滞剂的使用和剂量[相对于指南推荐的维持剂量（GRD）]。“保持低”定义为在两个时间点都<50%GRD,\'保持高\'为≥50%GRD,和“向上滴定”和“向下滴定”作为剂量轨迹。在1110名患者中（平均年龄63±13岁，16%的女性，26%纽约心脏协会III/IV级)，714（64％）是来自新加坡的多种族亚洲人，396来自新西兰（主要是欧洲种族）。ACEis/ARBs或β受体阻滞剂的基线使用率很高（87％）。>80%的患者服用了环状利尿剂，盐皮质激素受体拮抗剂在大约一半的患者，和他汀类药物在>90％的患者。在基线,只有11%和9%的药物类别获得了100%的GRD，分别,大约一半（47%）的ACEis/ARBs或β受体阻滞剂达到≥50%的GRD。6个月时,绝大多数人仍处于“保持低位”类别，三分之一保持在“保持高位”，而10-16%的向上滴定和4-6%的向下滴定。患者较低（vs.较高）ACEis/ARBs和β受体阻滞剂的N末端β型利钠肽前体水平更有可能升高或处于“保持高水平”（P=0.002）。缺血性病因，既往HF住院，和新加坡的入学率(vs.对于规定剂量的ACEis/ARBs和β受体阻滞剂，新西兰）与“保持低”的可能性较高（所有P<0.005）独立相关。针对逆概率加权进行了调整，ACEis/ARBs≥100%GRD[风险比（HR）=0.42；95%置信区间（CI）0.24-0.73]，β受体阻滞剂≥50%GRD（HR=0.58；95%CI0.37-0.90）（与无）与1年复合结局的较低风险相关。注册国家没有修改剂量类别与1年复合结局的关联。更高的药物剂量与QoL的更大改善相关。
结论：尽管基线时HF药物使用率较高，大多数患者在6个月内未对这些药物进行上调.多种临床因素与药物剂量的变化有关。迫切需要进一步的研究来调查HF治疗缺乏上调的原因（及其频率），这可以为根据临床和生化参数及时上调HF治疗的策略提供信息。
结果：一项前瞻性多中心研究的HFrEF（左心室射血分数<40％）参与者在基线和6个月时检查了ACEis/ARB和β受体阻滞剂的使用和剂量[相对于指南推荐的维持剂量（GRD）]。“保持低”定义为在两个时间点都<50%GRD,\'保持高\'为≥50%GRD,和“向上滴定”和“向下滴定”作为剂量轨迹。在1110名患者中（平均年龄63±13岁，16%的女性，26%纽约心脏协会III/IV级)，714（64％）是来自新加坡的多种族亚洲人，396来自新西兰（主要是欧洲种族）。ACEis/ARBs或β受体阻滞剂的基线使用率很高（87％）。>80%的患者服用了环状利尿剂，盐皮质激素受体拮抗剂在大约一半的患者，和他汀类药物在>90％的患者。在基线,只有11%和9%的药物类别获得了100%的GRD，分别,大约一半（47%）的ACEis/ARBs或β受体阻滞剂达到≥50%的GRD。6个月时,绝大多数人仍处于“保持低位”类别，三分之一保持在“保持高位”，而10-16%的向上滴定和4-6%的向下滴定。患者较低（vs.较高）ACEis/ARBs和β受体阻滞剂的N末端β型利钠肽前体水平更有可能升高或处于“保持高水平”（P=0.002）。缺血性病因，既往HF住院，和新加坡的入学率(vs.对于规定剂量的ACEis/ARBs和β受体阻滞剂，新西兰）与“保持低”的可能性较高（所有P<0.005）独立相关。针对逆概率加权进行了调整，ACEis/ARBs≥100%GRD[风险比（HR）=0.42；95%置信区间（CI）0.24-0.73]，β受体阻滞剂≥50%GRD（HR=0.58；95%CI0.37-0.90）（与无）与1年复合结局的较低风险相关。注册国家没有修改剂量类别与1年复合结局的关联。更高的药物剂量与QoL的更大改善相关。
结论：尽管基线时HF药物使用率较高，大多数患者在6个月内未对这些药物进行上调.多种临床因素与药物剂量的变化有关。迫切需要进一步的研究来调查HF治疗缺乏上调的原因（及其频率），这可以为根据临床和生化参数及时上调HF治疗的策略提供信息。
