Why the study?
While LDL-C is a well-established risk factor for ASCVD, its prognostic role in HFrEF remains controversial.
Does low baseline LDL-C (< 100 mg/dL) compared to high LDL-C (≥ 100 mg/dL) affect the risk of ischemic cardiovascular events or all-cause mortality in patients with chronic stable HFrEF?
Observational (n=1,274)
Yes
Does low baseline LDL-C (< 100 mg/dL) compared to high LDL-C (≥ 100 mg/dL) affect the risk of ischemic cardiovascular events or all-cause mortality in patients with chronic stable HFrEF?
Effect estimate: HR 1.57 (95% CI 1.15-2.16)
p-value: p=0.005
In patients with chronic stable HFrEF, lower baseline LDL-C (< 100 mg/dL) is associated with higher all-cause mortality but not with a reduction in ischemic events, challenging the uniform application of intensive lipid-lowering strategies in this population.
BACKGROUND: While low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), its prognostic role in heart failure with reduced ejection fraction (HFrEF) remains controversial. This study aimed to investigate the association between baseline LDL-C levels and ischemic cardiovascular events or all-cause mortality in HFrEF patients, with further stratification by ischemic or non-ischemic etiology. METHODS: Using data from the HF-ACTION trial, we analyzed 1,274 patients with chronic stable HFrEF, categorized into low LDL-C (< 100 mg/dL) and high LDL-C (≥ 100 mg/dL) groups. The primary endpoints were a composite of ischemic cardiovascular events (myocardial infarction, unstable angina, ischemic stroke, or transient ischemic attack) and all-cause mortality. Cox proportional hazards and Fine-Gray competing risk models were employed to assess the association between LDL-C and outcomes, with subgroup analysis by HF etiology. RESULTS: >0.05). CONCLUSION: In chronic stable HFrEF, lower baseline LDL-C (< 100 mg/dL) is associated with higher all-cause mortality but not with ischemic events. The net benefit of lipid-lowering therapy in ischemic HFrEF remains uncertain and merits validation in phenotype-specific randomized trials.
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Wang et al. (2025) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=1,274). Low LDL-C (< 100 mg/dL) vs. High LDL-C (≥ 100 mg/dL) was evaluated on All-cause mortality (HR 1.57, 95% CI 1.15-2.16, p=0.005).
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