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Similar Impact of Clopidogrel or Ticagrelor on Carotid Atherosclerotic Plaque Inflammation.

ABSTRACT: BACKGROUND:Platelets play an important role in inflammation. Inhibitors of the P2Y12 receptor, which is involved in platelet activation, may have a direct effect on carotid atherosclerotic plaque inflammation. HYPOTHESIS:We compared the effects of clopidogrel and ticagrelor therapy for carotid atherosclerotic plaque inflammation using 18 F-fluorodeoxyglucose ( 18 FDG) positron emission tomography (PET) imaging. METHODS:Fifty patients with acute coronary syndrome and ?1 18 FDG uptake in the carotid artery (target-to-background ratio [TBR] ?1.6) were randomized to either clopidogrel or ticagrelor groups. Of these, 46 completed PET examinations at baseline and at 6 months. The primary endpoint was the percent change in TBR of the index vessel at the most diseased segment (MDS). RESULTS:Baseline characteristics were similar between the 2 groups. At 6-month follow-up, low-density lipoprotein cholesterol and C-reactive protein significantly decreased in both groups (P < 0.001). The TBR of the index vessel and aorta significantly decreased in both groups (P < 0.01). The percent change in the MDS TBR of the index vessel was numerically but not significantly lower in the clopidogrel group than in the ticagrelor group (-9.5?±?14.6% vs -13.5?±?19.3%; P = 0.427). Likewise, the percent change in the whole-vessel TBR of the index vessel was not different between the 2 groups (P = 0.166). Similar findings were observed for changes in the MDS TBR (P = 0.412) or whole-vessel TBR of the aorta (P = 0.363). CONCLUSIONS:Carotid atherosclerotic plaque inflammation significantly decreases to a similar degree following 6 months of either clopidogrel or ticagrelor treatment.

SUBMITTER: Oh M

PROVIDER: S-EPMC6490841 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Similar Impact of Clopidogrel or Ticagrelor on Carotid Atherosclerotic Plaque Inflammation.

Oh Minyoung M Lee Cheol Whan CW Lee Hyo Sang HS Chang Mineok M Ahn Jung-Min JM Park Duk-Woo DW Kang Soo-Jin SJ Lee Seung-Whan SW Kim Young-Hak YH Moon Dae Hyuk DH Park Seong-Wook SW Park Seung-Jung SJ

Clinical cardiology 20160726 11

<h4>Background</h4>Platelets play an important role in inflammation. Inhibitors of the P2Y<sub>12</sub> receptor, which is involved in platelet activation, may have a direct effect on carotid atherosclerotic plaque inflammation.<h4>Hypothesis</h4>We compared the effects of clopidogrel and ticagrelor therapy for carotid atherosclerotic plaque inflammation using <sup>18</sup> F-fluorodeoxyglucose ( <sup>18</sup> FDG) positron emission tomography (PET) imaging.<h4>Methods</h4>Fifty patients with ac ...[more]

PMID: 27459273

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Project description:ObjectiveThere is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated.Materials and methodsTwenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat's pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated.ResultsA trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 ?m(2) [interquartile range {IQR} 454,778-603,925 ?m(2)] versus ticagrelor, n=13, 462,595 ?m(2) [IQR 379,740-546,037 ?m(2)]; P=0.1). A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4-0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31-0.39]; P=0.008), and a significant increase in fibrous caps thickness (control, n=11, 3.7 ?m [IQR 3.4-4.2 ?m] versus ticagrelor, n=13, 4.7 [IQR 4.3-5.5 ?m], P=0.04) were seen in ticagrelor-treated mice. In vitro studies demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07±0.03 versus ticagrelor 0.03±0.03; P=0.0002) when incubated with ticagrelor. Uptake of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor (control 9.2 [IQR 5.3-12.9] versus ticagrelor 6.4 [IQR 2.5-9.5], P=0.02).ConclusionThe present study demonstrates for the first time a plaque-stabilizing effect of ticagrelor in a model of advanced vascular disease, potentially induced by a reduction of oxLDL uptake or an inhibition of apoptosis as seen in vitro.

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Similar Impact of Clopidogrel or Ticagrelor on Carotid Atherosclerotic Plaque Inflammation.

Publications

Similar Impact of Clopidogrel or Ticagrelor on Carotid Atherosclerotic Plaque Inflammation.

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