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J Thromb Thrombolysis. 2016 May;41(4):656-62. doi: 10.1007/s11239-015-1285-4.

Evaluation of the F2R IVS-14A/T PAR1 polymorphism with subsequent cardiovascular events and bleeding in patients who have undergone percutaneous coronary intervention.

Author information

1
Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
2
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
3
Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
4
Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
5
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
6
Vanderbilt Heart and Vascular Institute, 2220 Pierce Avenue, 383 PRB, Nashville, TN, 37232-6300, USA.
7
Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA. john.cleator@vanderbilt.edu.
8
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. john.cleator@vanderbilt.edu.
9
Vanderbilt Heart and Vascular Institute, 2220 Pierce Avenue, 383 PRB, Nashville, TN, 37232-6300, USA. john.cleator@vanderbilt.edu.

Abstract

Abnormal platelet reactivity is associated with recurrent ischemia and bleeding following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR1), encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR1 receptor density and function. We hypothesized that carriers of the T allele, who have been shown to have decreased platelet reactivity, would be at lower risk for thrombotic events, but higher risk for bleeding following PCI. Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record, we studied 660 patients who underwent PCI for unstable or stable coronary artery disease. Primary outcome measures were major adverse cardiovascular events (MACE, composite of revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research Consortium scale) over 24 months. The minor allele (T) frequency was 14.8 %. There were no genotypic differences in the frequency of MACE (33.7, 28.8, and 31.6 % for A/A, A/T, and T/T respectively, P = 0.50) or bleeding (15.7, 14.7, and 18.8 % for A/A, A/T, and T/T respectively, P = 0.90). In a Cox regression model, fully adjusted for age, race, sex, BMI, and smoking status, carrying a T allele was not associated with MACE (HR 1.19, 95 % CI 0.89-1.59, P = 0.23) or bleeding (HR 0.73, 95 % CI 0.37-1.4, P = 0.34). In conclusion, in our population, F2R IVS-14 PAR1 variability does not affect risk of MACE or bleeding following PCI.

KEYWORDS:

Bleeding; Ischemia; PAR-1; PAR1; PCI; Percutaneous coronary intervention; Protease-activated receptor-1; Thrombosis

PMID:
26446588
DOI:
10.1007/s11239-015-1285-4
[Indexed for MEDLINE]

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