Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.
Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.
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DOI：
10.1001/jama.2016.10260
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发表时间：
2016-08-02
影响因子：
120.7
通讯作者：
Cappola, Thomas P.
中科院分区：
文献类型：
--
作者：
Margulies, Kenneth B.;Hernandez, Adrian F.;Redfield, Margaret M.;Givertz, Michael M.;Oliveira, Guilherme H.;Cole, Robert;Mann, Douglas L.;Whellan, David J.;Kiernan, Michael S.;Felker, G. Michael;McNulty, Steven E.;Anstrom, Kevin J.;Shah, Monica R.;Braunwald, Eugene;Cappola, Thomas P.
心脏代谢异常导致左心室射血分数（LVEF）降低的晚期心力衰竭的病理生理学。胰高血糖素样肽1（GLP-1）激动剂已在晚期心力衰竭患者的早期临床研究中显示出心脏保护作用，而与2型糖尿病状态无关。检测GLP-1激动剂治疗是否可改善急性心力衰竭住院后的临床稳定性。在近期住院的已确诊心力衰竭和LVEF降低患者中进行的II期、双盲、安慰剂对照、随机化临床试验。患者于2013年8月至2015年3月在24家美国研究中心入组。GLP-1激动剂利拉鲁肽（n = 154）或安慰剂（n = 146），每日皮下注射;在前30天内，研究药物剂量增至1.8 mg/d（如耐受），并持续180天。主要终点是一个总体等级评分，其中所有患者，无论治疗分配如何，均在3个分层中进行分级：至死亡时间、至因心力衰竭再住院时间和N末端B型利钠肽前体水平从基线至180天的时间平均比例变化。值越高表示健康状况越好（稳定性）。探索性次要结局包括主要终点成分、心脏结构和功能、6分钟步行距离、生活质量和联合事件。在随机分配的300名患者中，（中位年龄，61岁[四分位距{IQR}，52-68岁]; 64名[21%]女性; 178名[59%]患有2型糖尿病;中位LVEF为25% [IQR，19%-33%];中位N末端B型利钠肽原水平为2049 pg/mL [IQR，1054-4235 pg/mL]），271例完成研究。与安慰剂相比，利拉鲁肽对主要终点无显著影响（利拉鲁肽组的平均秩为146，安慰剂组为156，P = 0.31）。死亡人数没有显著的组间差异（利拉鲁肽组19例[12%] vs安慰剂组16例[11%];风险比，1.10 [95% CI，0.57-2.14]; P = 0.78）或因心力衰竭再次住院（分别为63 [41%] vs 50 [34%];风险比，1.30 [95%CI，0.89-1.88]; P = 0.17）或探索性次要终点。在糖尿病患者中预先设定的亚组分析未显示任何显著的组间差异。利拉鲁肽组和安慰剂组分别有16例（10%）和27例（18%）报告的促发剂高血糖事件，低血糖事件不常见（分别为2例[1%]和4例[3%]）。在近期因心力衰竭和LVEF降低住院的患者中，使用利拉鲁肽并未导致更高的住院后临床稳定性。这些结果不支持在这种临床情况下使用利拉鲁肽。clinicaltrials.gov标识符：NCT 01800968
Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52–68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%–33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054–4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57–2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89–1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively). Among patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation. clinicaltrials.gov Identifier: NCT01800968
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DOI：
10.1016/s0735-1097(97)00185-x
发表时间：
1997-08-01
影响因子：
24
作者：
Swan, JW;Anker, SD;Coats, AJS
通讯作者：
Coats, AJS
影响因子：
3.1
作者：
Wu, Shiying;Hopper, Ingrid;Krum, Henry
通讯作者：
Krum, Henry
影响因子：
6
作者：
Sokos, George G.;Nikolaidis, Lazaros A.;Shannon, Richard P.
通讯作者：
Shannon, Richard P.
DOI：
10.2174/1568008054064869
发表时间：
2005-06-05
期刊：
Current Drug Targets - Immune Endocrine and Metabolic Disorders
影响因子：
--
作者：
Abel, E. Dale
通讯作者：
Abel, E. Dale
影响因子：
9.3
作者：
Clarke SJ;McCormick LM;Dutka DP
通讯作者：
Dutka DP