Liraglutide had consistent effects on major adverse cardiovascular events in patients with (HR 0.81; 95% CI 0.65-1.02) and without (HR 0.88; 95% CI 0.78-1.00) a history of heart failure.
RCT (n=9,340)
Double-blind
1:1
Yes
Does liraglutide reduce major adverse cardiovascular events in patients with type 2 diabetes and high cardiovascular risk, with or without a history of heart failure?
Liraglutide safely reduces cardiovascular events and mortality in patients with type 2 diabetes and high cardiovascular risk, with consistent benefits regardless of baseline heart failure history (NYHA I-III).
Effect estimate: HR 0.81 (with HF); HR 0.88 (without HF) (95% CI 0.65-1.02 (with HF); 0.78-1.00 (without HF))
p-value: p interaction = 0.53
BACKGROUND More data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required. OBJECTIVES The purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history. METHODS In the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted. RESULTS At baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio HR: 0.81 95% confidence interval (CI): 0.65 to 1.02) and without (HR: 0.88 95% CI: 0.78 to 1.00) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 95% CI: 0.70 to 1.14 with HF; HR: 0.83 95% CI: 0.70 to 0.97 without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 95% CI: 0.75 to 1.28 with HF; HR: 0.78 95% CI: 0.61 to 1.00 without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 95% CI: 0.74 to 1.15) and without (HR: 0.77 95% CI: 0.65 to 0.91) a history of HF (p interaction = 0.19). CONCLUSIONS Based on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results LEADER; NCT01179048).
“There are really two different ways to apply these medications. One is to reduce CVD death and heart failure and the other is, if you will, 'athero-prevention.' Quite simply, in my practice—and this is how I've translated this data and have since these trials were published—if you have a diabetic patient whose history is one of myocardial infarction or stroke and you're worried about recurrent ischemic events, I would lean more towards liraglutide. On the other hand, if they have heart failure or are at increased risk for heart failure readmission, I think a SGLT2 inhibitor is the way to go. That strategy hasn't been studied in clinical studies, but it's a rational way to think about how one might use these agents in practice.”
Marso et al. (2020) conducted an RCT in Type 2 diabetes and high cardiovascular risk (n=9,340). Liraglutide vs. Placebo plus standard care was evaluated on Time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.81 (with HF); HR 0.88 (without HF), 95% CI 0.65-1.02 (with HF); 0.78-1.00 (without HF), p=p interaction = 0.53). Liraglutide had consistent effects on major adverse cardiovascular events in patients with (HR 0.81; 95% CI 0.65-1.02) and without (HR 0.88; 95% CI 0.78-1.00) a history of heart failure.