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MiR-126-3P and MiR-223-3p in Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty, The Prague-18 Genetic Sub-study
Authors : M Hromadka (Plzen,CZ), Z Motovska (Prague,CZ), M Karpisek (Brno,CZ), O Hlinomaz (Brno,CZ), R Miklik (Brno,CZ), F Tousek (Ceske Budejovice,CZ), J Jarkovsky (Brno,CZ), R Rokyta (Plzen,CZ), I Krepelkova (Brno,CZ), J Izakova (Brno,CZ), P Widimsky (Prague,CZ)
M. Hromadka1
,
Z. Motovska2
,
M. Karpisek3
,
O. Hlinomaz4
,
R. Miklik5
,
F. Tousek6
,
J. Jarkovsky7
,
R. Rokyta1
,
I. Krepelkova3
,
J. Izakova3
,
P. Widimsky2
,
1Charles University and Univ. Hospital, Department of Cardiology - Plzen - Czechia
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2Charles University Prague, 3rd Faculty of Medicine, Faculty Hospital Kralovske Vinohrady - Prague - Czechia
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3Biovendor, Laboratory Medicine - Brno - Czechia
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4International Clinical Research Center, St. Anne's University Hospital - Brno - Czechia
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5Masaryk University, University hospital - Brno - Czechia
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6Regional Hospital of Ceske Budejovice - Ceske Budejovice - Czechia
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7Institute of Biostatistics and Analyses of Masaryk University - Brno - Czechia
,
Background: Balancing the intensity and duration of antiplatelet therapy according to thrombotic risk is a fundamental need in order to optimize therapy effectiveness and safety. Incorporation of new predictors in thrombotic risk stratification is therefore of a crucial importance for antiplatelet therapy net clinical benefit.
Purpose: The present analysis aimed to evaluate the relation of miR-126-3p and miR-223-3p, new markers of platelet activation, in order to facilitate prediction of recurrent thrombotic events after acute myocardial infarction (AMI).
Method: The analysis included 598 patients (age median 62 years, men 77.8%) randomized in the Prague-18 study (ticagrelor vs. prasugrel in AIM treated with primary PCI). During the study follow up, 40.6% of patients switched to clopidogrel. Determination of miR was evaluated 24 hours after admission; miR-126-3p and miR-223-3p were normalized by miR-423-3p and miR-150-5p. Quantitative determination of selected miRNAs was performed with a novel microRNA immunoassay method.
Selected miRNAs were compared with key efficacy endpoints (cardiovascular death, nonfatal MI and stroke), stent thrombosis and all hemorrhagic events, and analysed using univariate and multivariate logistic regressions.
Results: Increased values of miR-223-3p were significantly related to the occurrence of combined ischemic endpoint within 30 days [OR (95% CI) 15.739 (2.066; 119.932) p=0.008] and within one year [3.175 (1.40; 7.186) p=0.006]. Decreased ratio of miR-126-3P/miR-223-3p was significantly related to the occurrence of combined ischemic endpoint within 30 days [0.137 (0.031; 0.609) p=0.009] and one year [0.372 (0.169; 0.819) p=0.014]. MiRNAs were identified as independent predictors even after adjustment for confounding clinical predictors (Study arm, Switch to Clopidogrel, Age, Men, BMI, Smoking, History of Hyperlipidemia, Hypertension, DM, MI, PCI, CABG, Chronic heart failure, Chronic renal failure, Peripheral arterial disease, LBBB, RBBB, TIMI <3 after PCI, Number of diseased vessels >1, Stem disease, Suboptimal of failure of PCI, Time to hospital). Adjusted ORs (95% CI) are 11.828 (1.472; 98.011), p=0.022 and 2.394 (1.021; 5.610), p=0.045 for increased value of miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively; 0.151 (0.030; 0.757), p=0.022 and 0.407 (0.179; 0.925), p=0.032 for decreased ratio of miR-126–3P/miR-223-3p and the occurrence of combined ischemic endpoint within 30 days and one year respectively. No association between miRNA and bleeding complications was identified.
Conclusion: The miR-223-3p and miR-126-3p to miR-223-3p ratio are strong independent predictors of thrombotic ischemic events and can be used to stratify patients post AMI.
In line with the ESC mission, newly presented content is made available to all for a limited time (4 months for ESC Congress, 3 months for other events). ESC Professional Members, Association Members (Ivory & above) benefit from year-round access to all the resources from their respective Association, and to all content from previous years. Fellows of the ESC (FESC), and Professionals in training or under 40 years old, who subscribed to a Young Combined Membership package benefit from access to all ESC 365 content from all events, all editions, all year long. Find out more about ESC Memberships here.