Khan Muhammad Shahzeb, Greene Stephen J, Hellkamp Anne S, DeVore Adam D, Shen Xian, Albert Nancy M, Patterson J Herbert, Spertus John A, Thomas Laine E, Williams Fredonia B, Hernandez Adrian F, Fonarow Gregg C, Butler Javed
Division of Cardiology (M.S.K.), Duke University School of Medicine, Durham, NC.
Duke Clinical Research Institute, Durham, NC (S.J.G., A.S.H., A.D.D., L.E.T., A.F.H.).
Circ Heart Fail. 2021 Nov;14(11):e008351. doi: 10.1161/CIRCHEARTFAILURE.121.008351. Epub 2021 Oct 22.
Diuretics are a mainstay therapy for the symptomatic treatment of heart failure. However, in contemporary US outpatient practice, the degree to which diuretic dosing changes over time and the associations with clinical outcomes and health care resource utilization are unknown.
Among 3426 US outpatients with chronic heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure registry with complete medication data and who were prescribed a loop diuretic, diuretic dose increase was defined as: (1) change to a total daily dose higher than their previous total daily dose, (2) addition of metolazone to the regimen, (3) change from furosemide to either bumetanide or torsemide, and the change persists for at least 7 days. Adjusted hazard ratios or rate ratios along with 95% CIs were reported for clinical outcomes among patients with an increase in oral diuretic dose versus no increase in diuretic dose.
Overall, 796 (23%) had a diuretic dose increase (18 episodes per 100 patient-years). The proportion of patients with dyspnea at rest (38% versus 26%), dyspnea at exertion (79% versus 67%), orthopnea (32% versus 21%), edema (60% versus 43%), and weight gain (40% versus 23%) were significantly (all <0.001) higher in the diuretic increase group. Baseline angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (hazard ratio, 0.75 [95% CI, 0.65-0.87]) use were associated with lower likelihood of diuretic increase over time. Patients with a diuretic dose increase had a significantly higher number of heart failure hospitalizations (rate ratio, 2.53 [95% CI, 2.10-3.05]), emergency department visits (rate ratio, 1.84 [95% CI, 1.56-2.17]), and home health visits (rate ratio, 1.88 [95% CI, 1.39-2.54]), but not all-cause mortality (hazard ratio, 1.10 [95% CI, 0.89-1.36]). Similarly, greater furosemide dose equivalent increases were associated with greater resource utilization but not with mortality, compared with smaller increases.
In this contemporary US registry, 1 in 4 patients with heart failure with reduced ejection fraction had outpatient escalation of diuretic therapy over longitudinal follow-up, and these patients were more likely to have sign/symptoms of congestion. Outpatient diuretic dose escalation of any magnitude was associated with heart failure hospitalizations and resource utilization, but not all-cause mortality.
利尿剂是心力衰竭症状性治疗的主要手段。然而，在美国当代门诊实践中，利尿剂剂量随时间的变化程度以及与临床结局和医疗资源利用的关联尚不清楚。
在“改变心力衰竭患者管理”登记研究中，对3426例射血分数降低的美国慢性心力衰竭门诊患者进行分析，这些患者有完整的用药数据且被开具了袢利尿剂。利尿剂剂量增加定义为：（1）每日总剂量高于之前的每日总剂量；（2）治疗方案中加用美托拉宗；（3）从呋塞米改为布美他尼或托拉塞米，且这种变化持续至少7天。报告口服利尿剂剂量增加的患者与未增加利尿剂剂量的患者相比，临床结局的调整后风险比或率比以及95%置信区间。
总体而言，796例（23%）患者利尿剂剂量增加（每100患者年18次发作）。利尿剂增加组静息呼吸困难（38%对2%）、活动时呼吸困难（79%对67%）、端坐呼吸（32%对21%）、水肿（60%对43%）和体重增加（40%对23%）患者的比例显著更高（均P<0.001）。基线使用血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂（风险比，0.75[95%置信区间，0.65 - 0.87]）与随时间利尿剂增加的可能性较低相关。利尿剂剂量增加的患者心力衰竭住院次数显著更多（率比，2.53[95%置信区间，2.10 - 3.05]）、急诊就诊次数（率比，1.84[95%置信区间，1.56 - 2.17]）和家庭保健访视次数（率比，1.88[95%置信区间，1.39 - 2.54]），但全因死亡率无差异（风险比，1.10[95%置信区间，0.89 - 1.36]）。同样，与较小增加相比，更大的呋塞米等效剂量增加与更多的资源利用相关，但与死亡率无关。
在这个当代美国登记研究中，四分之一射血分数降低的心力衰竭患者在纵向随访期间门诊利尿剂治疗升级，这些患者更可能有充血的体征/症状。任何程度的门诊利尿剂剂量升级都与心力衰竭住院和资源利用相关，但与全因死亡率无关。
