Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis

Jan 25, 2023Cardiovascular drugs and therapy

How Past Heart Failure Affects Heart Benefits of GLP-1 Medicines in Type 2 Diabetes

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Abstract

Pooled analysis of 48,489 individuals with type-2 diabetes mellitus revealed that GLP-1 receptor agonist treatment significantly reduced the risk of heart failure hospitalizations and cardiovascular death in those without a history of heart failure.

GLP-1 receptor agonists reduced the risk of heart failure hospitalizations and cardiovascular death (HR = 0.84) in type-2 diabetes patients without a history of heart failure.
No significant reduction in heart failure hospitalizations and cardiovascular death (HR = 0.96) was observed in patients with a history of heart failure.
GLP-1 receptor agonists were associated with a reduced incidence of heart failure hospitalizations in both groups (HR = 0.89).
The benefits on major adverse cardiovascular events were consistent across all patients with type-2 diabetes, regardless of heart failure history.
The analysis indicated that baseline heart failure history may influence the effectiveness of GLP-1 receptor agonists on heart failure hospitalizations and cardiovascular death.

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PURPOSE: Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM.

METHODS: PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations and/or cardiovascular death (HHF/CVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPERO:CRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed.

RESULTS: We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHF/CVD in only T2DM without HF history (HR = 0.84; 95%CI, 0.77-0.91; I = 14%; p < 0.001), but not in those with HF history (HR = 0.96; 95%CI, 0.85-1.08; I = 14%; p = 0.4) (p-interaction < 0.1). GLP-1RAs reduced incident HHF in T2DM with or without HF history (HR = 0.89; 95%CI, 0.80-0.98; I = 41%; p < 0.05) (p-interaction = 0.28). Sensitivity analysis excluding REWIND trial accentuated the impact of baseline HF history on both HHF/CVD and HHF (p-interaction < 0.05). Benefits on MACE with GLP-1RAs were consistently seen in T2DM regardless of HF history (p-interaction = 0.8). 2 2 2

CONCLUSION: GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHF/CV death were observed in those with HF history.

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Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis

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