medwireNews: A post-hoc analysis of the LEADER trial suggests that liraglutide reduces cardiovascular (CV) risk in people with type 2 diabetes regardless of whether they have heart failure.
The glucagon-like peptide (GLP)-1 receptor agonist reduced both CV events and all-cause mortality in trial participants with and without heart failure, and there was no evidence of an increased risk for heart failure hospitalization.
However, the trial excluded patients who had severe heart failure (New York Heart Association functional class IV), and the author of a linked editorial, William Dec (Massachusetts General Hospital, Boston, USA), points out that 86% of LEADER participants had mild heart failure, of functional class I or II.
He suggests that this might explain why these positive findings contrast with those of the smaller LIVE and FIGHT randomized trials, which enrolled patients with moderate or severe heart failure and in which liraglutide did not improve heart failure outcomes relative to placebo. Indeed, patients taking liraglutide did worse on some endpoints.
And Dec writes in the Journal of the American College of Cardiology that “a substantial portion” of LEADER trial participants may have had heart failure with preserved ejection fraction, “a condition in which the effects of GLP-1 analogs remains unknown.”
The LEADER analysis included 1667 participants with heart failure at baseline (835 taking liraglutide) and 7673 without (3833 taking liraglutide). Those with heart failure had higher rates of CV and mortality endpoints overall, with 18.7% having a major adverse CV event (MACE), compared with 12.9% of those without; 13.0% versus 3.3% being hospitalized with heart failure; and 15.1% versus 7.5% dying of any cause.
But liraglutide was equally effective at reducing CV risk in both groups, report Steven Marso (Midwest Heart and Vascular Institute, Overland Park, Kansas, USA) and study co-authors. It reduced MACE by 19% and 12% versus placebo in patients with and without heart failure, respectively, and all-cause mortality by 11% and 17%, with no significant differences between the effect sizes in these patient subgroups.
Heart failure hospitalization was reduced by just 2% with liraglutide versus placebo in those who had the condition at baseline, compared with 22% in those without, but neither reduction was statistically significant and again there was no statistical difference between the two.
“The findings from the LEADER trial suggest that liraglutide is at least safe and potentially beneficial in lowering the rate of adverse cardiac events among [heart failure] patients,” writes Dec in his editorial.
“However, findings from ongoing, statistically more robust randomized clinical trials will determine whether liraglutide, another GLP-1 [analog], or the rapidly expanding class of [sodium-glucose cotransporter 2] inhibitors will ‘lead’ adjunctive diabetic management among established [heart failure] patients.”
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J Am Coll Cardiol 2020; 75: 1128–1141
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