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.
Conclusion
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.
References
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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.
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