Low LDL-C levels tied to increased risk of bleeding in stroke patients receiving DAPT: JAMA

“At three months, there were 270 (3.63%) bleeding events, and LDL-C below 70 mg/dL was linked with an increased risk of any bleeding and severe or moderate bleeding, with the risk of any bleeding risk increased at lower LDL-cholesterol levels in the ticagrelor-aspirin group.” the researchers wrote in their study published in JAMA Neurology.

No increased risk of any bleeding was seen in the clopidogrel-aspirin group. There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the clopidogrel-aspirin or ticagrelor-aspirin group.

Low-density lipoprotein cholesterol (LDL-C) is associated independently with ischemic stroke risk. Despite the efficacy of low LDL-C levels in reducing recurrent stroke risk, some observational studies have revealed that lowering LDL-C might contribute to an increased risk of hemorrhagic events, particularly hemorrhagic stroke. Additionally, the findings of a Mendelian randomization study support a possible causal relationship between LDL-C and intracranial hemorrhage (ICH).

Evidence remains sparse on the bleeding risk associated with LDL-C levels in patients receiving dual antiplatelet therapy (DAPT). Therefore, Aichun Cheng, Capital Medical University, Beijing, China, and colleagues aimed to investigate the association of LDL-C levels with bleeding risk in patients with high-risk transient ischemic attack (HRTIA) or minor ischemic stroke (MIS) receiving DAPT.

For this purpose, the researchers analyzed pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China comprising patients with MIS or HRTIA who were receiving DAPT: the CHANCE trial enrolled patients at 114 sites from 2009 to 2012, and HANCE-2 enrolled patients at 202 centers from 2019 to 2021. Patients from both the trials were followed for 90 days.

Exposures were baseline LDL-cholesterol levels and receipt of clopidogrel-aspirin and ticagrelor-aspirin DAPT.

The study’s primary outcome was any bleeding, and the secondary outcome included severe or moderate bleeding within three months after randomization. The association of LDL-C levels and all outcomes was assessed.

In the two trials, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included, 1066 without serum specimens, and 490 patients with missing baseline LDL-C value were excluded. Finally, the study included 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group). The median age was 64.32 years, and 33.32% were women.

Based on the study, the researchers reported the following findings:

• A total of 270 (3.63%) bleeding events were reported at three months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48) and severe or moderate bleeding (aHR, 2.78).
• The risk of any bleeding was raised at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71). However, an increased risk of any bleeding was not seen in the clopidogrel-aspirin group (aHR, 1.30).
• There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group.

In conclusion, the findings suggest that low levels of LDL-cholesterol are associated with an increased risk of bleeding within three months among MIS or HRTIA patients receiving DAPT, particularly those taking ticagrelor-aspirin.

“Weighing the benefits and risks is important when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients,” the researchers wrote.

Reference:

Cheng A, Xue J, Wang A, et al. LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA. JAMA Neurol. Published online March 04, 2024. doi:10.1001/jamaneurol.2024.0086