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.
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。