Dataset Information

Platelet CD40 ligand and bleeding during P2Y12 inhibitor treatment in acute coronary syndrome.

ABSTRACT: Antiplatelet therapy through inhibition of the adenosine diphosphate (ADP)/P2Y12 pathway is commonly used in the treatment of acute coronary syndrome (ACS). Although efficient in preventing platelet activation and thrombus formation, it increases the risk of bleeding complications. In patients with ACS receiving platelet aggregation inhibitors, that is, P2Y12 blockers (n = 923), we investigated the relationship between plasma and platelet-associated CD40L levels and bleeding events (n = 71). Treatment with P2Y12 inhibitors in patients with ACS did not affect plasma-soluble CD40L levels, but decreased platelet CD40L surface expression (pCD40L) and platelet-released CD40L (rCD40L) levels in response to stimulation as compared to healthy controls. In vitro inhibition of the ADP pathway in healthy control platelets reduced both pCD40L and rCD40L levels. In a multivariable analysis, the reduced pCD40L level observed in ACS patients was significantly associated with the risk of bleeding occurrence (adjusted odds ratio = 0.15; 95% confidence interval = 0.034-0.67). P2Y12 inhibitor-treated (ticagrelor) mice exhibited a 2.5-fold increase in tail bleeding duration compared with controls. A significant reduction in bleeding duration was observed on CD40L+/+ but not CD40L-/- platelet infusion. In addition, CD40L blockade in P2Y12 inhibitor-treated blood samples from a healthy human reduced thrombus growth over immobilized collagen under arterial flow. In conclusion, measurement of pCD40L may offer a novel approach to assessing bleeding risk in patients with ACS who are being treated with P2Y12 inhibitors.

SUBMITTER: Grosdidier C

PROVIDER: S-EPMC6781928 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundEast Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel.MethodsThis study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays.ResultsAt the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020).ConclusionsOPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.

Project description:Aim: To assess platelet (PLT) function and bleeding risks in patients with acute coronary syndrome after tirofiban infusion. Methods: Patients diagnosed with acute coronary syndrome from May 2016 to February 2018 in the Department of Cardiac Intensive Care Unit, Zhongshan Hospital, were enrolled. They were symmetrically allocated into two groups: tirofiban treatment group or control group (without tirofiban treatment). Blood samples were collected 24 h postoperation for the evaluation of antiplatelet effect of tirofiban. We applied thromboelastography to detect on-treatment PLT reactivity and conducted laboratory tests to assess the risk of bleeding following tirofiban treatment. After discharge, telephone follow-up and outpatient interview were carried out. The primary clinical endpoint was major adverse cardiovascular events, including cardiovascular death, cardiovascular mortality, myocardial infarction, and revascularization for the targeted vascular lesion. Results: There were a total of 196 patients with acute coronary syndrome after screening with the inclusion criteria and the exclusion criteria. Ninety-eight patients were assigned to receive either tirofiban treatment or control treatment. Patients treated with tirofiban had more coronary lesions and stents implanted compared with the control group (P = 0.000). After tirofiban infusion, inhibition of platelet aggregation induced by thromboxane A2 and adenosine diphosphate was significantly higher compared to patients without tirofiban infusion (80.3% ± 19.6% vs. 72.6% ± 13.0%, P = 0.002; and 81.0% ± 19.8% vs. 75.4% ± 12.4%, P = 0.020, respectively). There was no significant difference in the reduction of hemoglobin (Hb), hematocrit (Hct), and PLT after administration of tirofiban, compared with baseline (P > 0.05). In addition, no significant differences were identified between the two groups with respect to Hb, Hct, and PLT after tirofiban infusion. However, C-reactive protein level, referred to as an inflammation marker, was significantly lowered after infusion tirofiban compared with the control group (11.9 ± 14.2 vs. 17.9 ± 21.2, P = 0.020). During the 1-year follow-up, the incidence rate of major adverse cardiovascular events remains indiscriminate between the two groups (P = 0.208). The assessments of cardiac biomarkers showed that tirofiban could decrease incidence of procedural myocardial infarction (odds ratio [OR] = 0.250, 95% confidence interval [CI] = 0.067-0.925, P = 0.027). At follow-up, the morbidity of left atrial dilation in tirofiban-treated patients, defined as enlargement of left atrial diameter >40mm, was lower compared to the control group (OR = 0.533, 95% CI = 0.301-0.945, P = 0.031). Conclusion: Tirofiban infusion could decrease PLT activation in patients with acute coronary syndrome without increasing the risk of bleeding. As a concomitant medication, tirofiban shows no benefit in reducing the occurrence of major adverse cardiovascular events.

Dataset Information

Platelet CD40 ligand and bleeding during P2Y12 inhibitor treatment in acute coronary syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets