Greene Stephen J, Butler Javed, Hellkamp Anne S, Spertus John A, Vaduganathan Muthiah, Devore Adam D, Albert Nancy M, Patterson J Herbert, Thomas Laine, Williams Fredonia B, Hernandez Adrian F, Fonarow Gregg C
Duke Clinical Research Institute, Durham, North Carolina; Division of Cardiology, Duke University School of Medicine, Durham, North Carolina.
Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
J Card Fail. 2022 Mar;28(3):370-384. doi: 10.1016/j.cardfail.2021.08.023. Epub 2021 Nov 15.
The comparative effectiveness of differing dosages of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) on clinical and patient-reported outcomes in clinical practice in the United States is unknown. This study sought to characterize associations between the dosing of GDMT and outcomes for patients with HFrEF in U.S. clinical practice.
This analysis included 4832 outpatients who had chronic HFrEF across 150 practices in the U.S. in the Change the Management of Patients with Heart Failure (CHAMP-HF) registry with no contraindication and available dosing data for at least 1 GDMT at baseline. Baseline dosing of angiotensin-converting enzyme (ACEI)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) therapies were examined. For each medication class, multivariable models assessed associations between medication dosing and clinical outcomes over 24 months (all-cause mortality, HF hospitalization) and patient-reported outcomes at 12 months (change in the Kansas City Cardiomyopathy Questionnaire Overall Summary score [KCCQ-OS]).
After adjustment, compared with target dosing, lower dosing was associated with higher all-cause mortality for ACEIs/ARBs/ARNIs (50% to < 100% target dosage, HR 1.16 [95% CI 0.87-1.55]; < 50% target dosage, HR 1.37 [95% CI 1.05-1.79]; none, HR 1.75 [95% CI 1.32-2.34; overall P< 0.001) and beta-blockers (50% to < 100% target dosage, HR 1.30 [95% CI 1.00-1.69]; < 50% target dosage, HR 1.41 [95% CI 1.11-1.79; none, HR 1.24 [95% CI 0.92-1.67]; overall P= 0.042). Lower dosing of ACEIs/ARBs/ARNIs was independently associated with higher risk of HF hospitalization (50% to < 100% target dosage, HR 1.08 [95% CI 0.90-1.30]; < 50% target dosage, HR 1.23 [1.04-1.47]; none, HR 1.29 [1.04-1.60]; overall P= 0.046), but beta-blocker dosing was not (overall P= 0.085). Target dosing of MRAs was not associated with risk of mortality or HF hospitalization. For each GDMT, compared with target dosing, lower dosing was not associated with change in the KCCQ-OS at 12 months, with the potential exception of worsening KCCQ-OS scores with lower dosing of ACEIs/ARBs/ARNIs.
In this contemporary U.S. outpatient HFrEF registry, target dosing of ACEI/ARB/ARNI and beta-blocker therapy was associated with reduced mortality and was variably associated with HF hospitalization and patient-reported outcomes. MRA dosing was not associated with outcomes. The totality of these findings support the benefits of target dosing of GDMT in routine practice, as tolerated, with unmeasured differences among patients receiving differing dosages potentially explaining the differing results seen here compared with randomized clinical trials.
在美国临床实践中，不同剂量的射血分数降低的心力衰竭（HFrEF）指南指导药物治疗（GDMT）对临床和患者报告结局的比较有效性尚不清楚。本研究旨在描述美国临床实践中GDMT剂量与HFrEF患者结局之间的关联。
本分析纳入了美国150家医疗机构中4832例慢性HFrEF门诊患者，这些患者来自心力衰竭患者管理改变（CHAMP-HF）登记处，无用药禁忌，且基线时至少有一种GDMT有可用的剂量数据。研究检查了血管紧张素转换酶（ACEI）/血管紧张素II受体阻滞剂（ARB）/血管紧张素受体脑啡肽酶抑制剂（ARNI）、β受体阻滞剂和盐皮质激素受体拮抗剂（MRA）疗法的基线剂量。对于每类药物，多变量模型评估了药物剂量与24个月内的临床结局（全因死亡率、心力衰竭住院）以及12个月时患者报告结局（堪萨斯城心肌病问卷总体总结评分[KCCQ-OS]的变化）之间的关联。
调整后，与目标剂量相比，ACEI/ARB/ARNI较低剂量与全因死亡率较高相关（50%至<100%目标剂量，HR 1.16[95%CI 0.87-1.55]；<50%目标剂量，HR 1.37[95%CI 1.05-1.79]；未用药，HR 1.75[95%CI 1.32-2.34]；总体P<0.001）以及β受体阻滞剂（50%至<100%目标剂量，HR 1.30[95%CI 1.00-1.69]；<50%目标剂量，HR 1.41[95%CI 1.11-1.79]；未用药，HR 1.24[95%CI 0.92-1.67]；总体P=0.042）。ACEI/ARB/ARNI较低剂量与心力衰竭住院风险较高独立相关（50%至<100%目标剂量，HR 1.08[95%CI 0.90-1.30]；<50%目标剂量，HR 1.2
