Low LDL Cholesterol Linked to Higher Bleeding Risk in VTE Patients on Anticoagulants: JAMA
Italy: A study published in JAMA Network Open has revealed that patients with low levels of low-density lipoprotein cholesterol (LDL-C) face a higher risk of bleeding while undergoing anticoagulation therapy for venous thromboembolism (VTE).
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
