The Influence of Liraglutide for Heart Failure: A Meta-Analysis of Randomized Controlled Trials
DOI:
https://doi.org/10.1532/hsf.2513Abstract
Introduction: The efficacy of liraglutide to treat heart failure remains controversial. We conducted a systematic review and meta-analysis to explore the influence of liraglutide on heart failure.
Methods: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through March 2018 for randomized controlled trials (RCTs) assessing the effect of liraglutide on cardiac function of heart failure. Meta-analysis is performed using the random-effect model.
Results: Four RCTs involving 629 patients are included in the meta-analysis. Overall, compared with the control group for heart failure, liraglutide treatment significantly can reduce NT-proBNP (Std. MD = -3.06; 95% CI = -5.78 to -0.34;
P = .03), and improve 6MWT (Std. MD=1.10; 95% CI = 0.75 to 1.44; P < .00001), but has no remarkable influence on LVEF change (Std. MD=1.10; 95% CI = -1.97 to 3.98;
P = 0.51), LVEDV change (Std. MD = 6.26; 95% CI = -1.45 to 13.97; P = .11), LVESV change (Std. MD = -13.47; 95% CI = -31.04 to 4.10; P = .13), hospitalization for heart failure (RR = 1.18; 95% CI = 0.88 to 1.58; P = .27), major adverse cardiovascular events (RR = 1.55; 95% CI = -0.24 to 9.89; P = .64), and cardiac death (RR = 1.11; 95% CI = 0.61 to 2.04; P = .72).
Conclusions: Liraglutide treatment has an important ability to reduce NT-proBNP and improve 6MWT for heart failure, but shows no important influence on LVEF, LVEDV, LVESV, hospitalization for heart failure, major adverse cardiovascular events, and cardiac death.
References
Bethel MA, Patel RA, Merrill P, Lokhnygina Y, Buse JB, Mentz RJ, et al. 2018. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. The lancet Diabetes & endocrinology. 6:105-13.
Bonsu KO, Arunmanakul P, Chaiyakunapruk N. 2018. Pharmacological treatments for heart failure with preserved ejection fraction-a systematic review and indirect comparison. Heart failure reviews.
Chanchai R, Kanjanavanit R, Leemasawat K, Amarittakomol A, Topaiboon P, Phrommintikul A. 2018. Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic. Journal of drug assessment. 7:8-13.
Chang G, Zhang D, Yu H, Zhang P, Wang Y, Zheng A, et al. 2013. Cardioprotective effects of exenatide against oxidative stress-induced injury. International journal of molecular medicine. 32:1011-20.
Chatterjee P, Joynt Maddox KE. 2018. US National Trends in Mortality From Acute Myocardial Infarction and Heart Failure: Policy Success or Failure? JAMA cardiology.
Chen WR, Hu SY, Chen YD, Zhang Y, Qian G, Wang J, et al. 2015. Effects of liraglutide on left ventricular function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. American heart journal. 170:845-54.
Chen WR, Shen XQ, Zhang Y, Chen YD, Hu SY, Qian G, et al. 2016. Effects of liraglutide on left ventricular function in patients with non-ST-segment elevation myocardial infarction. Endocrine. 52:516-26.
Chen WR, Tian F, Chen YD, Wang J, Yang JJ, Wang ZF, et al. 2016. Effects of liraglutide on no-reflow in patients with acute ST-segment elevation myocardial infarction. International journal of cardiology. 208:109-14.
Dokken BB, La Bonte LR, Davis-Gorman G, Teachey MK, Seaver N, McDonagh PF. 2011. Glucagon-like peptide-1 (GLP-1), immediately prior to reperfusion, decreases neutrophil activation and reduces myocardial infarct size in rodents. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 43:300-5.
Drucker DJ. 2006. The biology of incretin hormones. Cell metabolism. 3:153-65.
Halbirk M, Norrelund H, Moller N, Holst JJ, Schmitz O, Nielsen R, et al. 2010. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. American journal of physiology Heart and circulatory physiology. 298:H1096-102.
Hemmingsen B, Sonne DP, Metzendorf MI, Richter B. 2017. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. The Cochrane database of systematic reviews. 5:CD012204.
Higgins JP, Thompson SG. 2002. Quantifying heterogeneity in a meta-analysis. Statistics in medicine. 21:1539-58.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. 1996. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clinical Trials. 17:1-12.
Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hanselmann A, et al. 2017. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. European journal of heart failure. 19:69-77.
Kavianipour M, Ehlers MR, Malmberg K, Ronquist G, Ryden L, Wikstrom G, et al. 2003. Glucagon-like peptide-1 (7-36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium. Peptides. 24:569-78.
Kjaergard LL, Villumsen J, Gluud C. 2001. Reported Methodologic Quality and Discrepancies between Large and Small Randomized Trials in Meta-Analyses. Annals of Internal Medicine. 135:982-9.
Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, et al. 2016. Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. Jama. 316:500-8.
Matsushita K, Harada K, Miyazaki T, Miyamoto T, Iida K, Tanimoto S, et al. 2018. Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction. Heart and vessels.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of clinical epidemiology. 62:1006-12.
Munaf M, Pellicori P, Allgar V, Wong K. 2012. A meta-analysis of the therapeutic effects of glucagon-like Peptide-1 agonist in heart failure. International journal of peptides. 2012:249827.
Nauck MA, Meier JJ, Cavender MA, Abd El Aziz M, Drucker DJ. 2017. Cardiovascular Actions and Clinical Outcomes With Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors. Circulation. 136:849-70.
Nielsen R, Jorsal A, Iversen P, Tolbod LP, Bouchelouche K, Sorensen J, et al. 2017. Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.
Nguyen TD, Shingu Y, Amorim PA, Schenkl C, Schwarzer M, Doenst T. 2018. GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved Ejection Fraction. Journal of cardiovascular translational research.
Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, et al. 2009. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 58:975-83.
Packer M. 2017. Will long-acting glucagon-like peptide-1 analogues recapitulate our agonizing experience with cyclic AMP-dependent positive inotropic agents in heart failure? European journal of heart failure.
Packer M. 2018. Does Neprilysin Inhibition Potentiate or Minimize the Adverse Effects of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Heart Failure? Journal of cardiac failure. 24:109-11.
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. 1999. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England journal of medicine. 341:709-17.
Santulli G. 2012. Coronary heart disease risk factors and mortality. Jama. 307:1137; author reply 8.
Scheen AJ. 2017. GLP-1 receptor agonists and heart failure in diabetes. Diabetes & metabolism. 43 Suppl 1:2S13-2S9.
Sorensen BM, Houben AJ, Berendschot TT, Schouten JS, Kroon AA, van der Kallen CJ, et al. 2016. Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study. Circulation. 134:1339-52.
Takahashi A, Ihara M, Yamazaki S, Asanuma H, Asakura M, Kitakaze M. 2015. Impact of Either GLP-1 Agonists or DPP-4 Inhibitors on Pathophysiology of Heart Failure. International heart journal. 56:372-6.
Tang ZH, Wang L, Zeng F, Zhang K. 2014. Association and predictive value analysis for metabolic syndrome on systolic and diastolic heart failure in high-risk patients. BMC cardiovascular disorders. 14:124.
Ussher JR, Drucker DJ. 2014. Cardiovascular actions of incretin-based therapies. Circulation research. 114:1788-803.
Vanderpool RR, Saul M, Nouraie M, Gladwin MT, Simon MA. 2018. Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction. JAMA cardiology.
Zhang L, Jaswal JS, Ussher JR, Sankaralingam S, Wagg C, Zaugg M, et al. 2013. Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. Circulation Heart failure. 6:1039-48.
Zhang JY, Wang XY, Wang X. 2017. Effects of liraglutide on hemodynamic parameters in patients with heart failure. Oncotarget. 8:62693-702.
