Low LDL Cholesterol Linked to Higher Bleeding Risk in VTE Patients on Anticoagulants: JAMA

The research, led by Dr. Carmine Siniscalchi and colleagues from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry, aimed to examine the link between LDL-C levels and bleeding complications during the initial 90 days of anticoagulation treatment for acute VTE. While LDL-C is a known target for cardiovascular risk reduction, its potential role in bleeding risk has not been explored thoroughly in this clinical setting.

For this purpose, the investigators performed a case-control analysis using data from over 19,000 VTE patients with available baseline LDL-C values between March 2009 and July 2024. Due to the non-routine nature of LDL-C testing, data were missing in approximately 75.6% of patients. However, a comparison of patient characteristics showed no major differences between those with and without available LDL-C measurements, minimizing concerns about selection bias.

The key findings of the study were as follows:

• Of 19,237 patients assessed, 2,502 (13%) had LDL-C levels below 70 mg/dL. These patients were generally older and more often male.
• They had a higher prevalence of hypertension, diabetes, prior arterial disease, anemia, and active cancer.
• A total of 743 patients (3.9%) experienced bleeding events within the 90-day follow-up period.
• Among these bleeding cases, 294 were major, 449 were nonmajor, and 32 were fatal.
• Patients with LDL-C levels below 70 mg/dL had a 40% higher risk of overall bleeding (AHR, 1.40).
• They also had a 49% higher risk of nonmajor bleeding (AHR, 1.49).
• Hematomas were the most frequently observed type of bleeding, with more than double the risk (AHR, 2.11).
• The increased bleeding risks were independent of statin use.

The authors acknowledged limitations, particularly the absence of LDL-C data for many patients and the inability to assess LDL-C changes over time. Nevertheless, the findings held strong even after adjusting for potential confounding variables.

The research emphasizes a previously underrecognized aspect of bleeding risk in patients on anticoagulants for VTE. Since LDL-C levels are not currently factored into conventional bleeding risk scores, the study suggests a potential role for incorporating lipid profiles into future risk stratification models.

"Further investigation is warranted to determine whether modifying treatment strategies based on LDL-C levels can help reduce bleeding complications in this population," the researchers concluded.

Reference:

Siniscalchi C, Meschi T, Di Micco P, et al. Low-Density Lipoprotein Cholesterol Levels and Bleeding Risk in Venous Thromboembolism. JAMA Netw Open. 2025;8(5):e259467. doi:10.1001/jamanetworkopen.2025.9467