Non-linear association between LDL-c levels and risk of in-hospital bleeding after PCI

LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS project

Literature - Yang Q, Sun D, Pei C et al. - Eur Heart J. 2021 Aug 31;42(33):3175-3186. doi: 10.1093/eurheartj/ehab418.

Introduction and methods

Bleeding events are the most common non-cardiac complication after PCI [1]. Some studies provided evidence for a potential link between cholesterol metabolism and platelet responsiveness [2,3]. This study investigated the relationships between LDL-c levels, major bleeds and net clinical outcome in a nationwide ACS registry.

The CCC-ACS project is an ongoing nationwide quality improvement project enrolling patients with ACS in China [4]. The current study included a total of 42378 ACS patients treated with PCI. In-hospital outcomes included a composite of major bleeds (BARC type 3b-3c and type 5, TIMI major bleeding or PLATO life-threatening major bleeding), ischemic events, in-hospital mortality, and net clinical outcome (any occurrence of major bleed, ischemic event or mortality). During a median hospital stay of 8 days (IQR 6-11 days), a total of 615 major bleeds, 218 ischemic strokes and 337 deaths were recorded.

Main results

  • A non-linear relationship was found for major bleeds, with a higher risk at lower LDL-c levels. LDL-c<70 mg/dL was associated with an increased major bleeding risk and net clinical outcome compared to LDL-c≥70 mg/dL in multivariable-adjusted logistic regression models (major bleeding: OR 1.49, 95%CI 1.21-1.84, P<0.001, absolute risk difference 0.63%; net clinical outcome: OR 1.34, 95%CI 1.14-1.58, P<0.001, absolute risk difference 0.76%).
  • There were no significant differences in ischemic events and mortality in patients with LDL-c<70 mg/dL compared to those with LDL-c≥70 mg/dL.
  • Every 30 mg/dL increase in the LDL-c categories from <40 to ≥160 mg/dL was associated with a 20% decrease in risk for hemorrhagic stroke after covariate adjustment (OR 0.80, 95%CI 0.66-0.97, P=0.021).
  • Use of ticagrelor was associated with increased probability of bleeding, compared to use of clopidogrel. The threshold value of LDL-c for increased bleeding risk was<54 mg/dL for clopidogrel-treated patients and <88 mg/dL for ticagrelor-treated patients. Type of P2Y12 inhibitor did not modify the risk for the net clinical outcome.
  • A linear relationship between glycoprotein IIb/IIa inhibitor and major bleeds as well as with net clinical outcome was observed, with a higher risk at lower LDL-c levels. Post-PCI anticoagulation was also associated with an increased bleeding risk at lower LDL-c levels.


This study in a nationwide ACS registry found a non-linear relationship between LDL-c levels and major in-hospital bleeds, with a higher risk at lower LDL-c levels in ACS patients after PCI. A threshold value of LDL-c<70 mg/dL was associated with an increased major bleeding risk and net clinical outcome in this population.


1. Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC. Defining high bleeding risk in patients undergoing percutaneous coronary intervention. Circulation 2019;140:240–261.

2. Iijima R, Ndrepepa G, Mehilli J, Byrne RA, Schulz S, Neumann FJ, Richardt G, Berger PB, Schomig A, Kastrati A. Profile of bleeding and ischaemic complications with bivalirudin and unfractionated heparin after percutaneous coronary intervention. Eur Heart J 2009;30:290–296.

3. Qi Z, Hu L, Zhang J, Yang W, Liu X, Jia D, Yao Z, Chang L, Pan G, Zhong H, Luo X, Yao K, Sun A, Qian J, Ding Z, Ge J. PCSK9 (proprotein convertase subtilisin/kexin 9) enhances platelet activation, thrombosis, and myocardial infarct expansion by binding to platelet CD36. Circulation 2021;143:45–61.

4. Hao Y, Liu J, Liu J, Smith SC Jr, Huo Y, Fonarow GC, Ma C, Ge J, Taubert KA, Morgan L, Guo Y, Zhang Q, Wang W, Zhao D; CCC-ACS Investigators. Rationale and design of the Improving Care for Cardiovascular Disease in China (CCC) project: a national effort to prompt quality enhancement for acute coronary syndrome. Am Heart J 2016;179:107–115.

Find this article online at Eur Heart J.

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