Received date: 22 Mar 2017
Accepted date: 05 Jul 2017
Published date: 20 Nov 2017
Copyright
OBJECTIVES and BACKGROUNDS: Cardiovascular events occure as a result of various risk factors, such as uric acid (UA), inflammation, hormones and other materials that induce C- reactive protein (CRP) expression. These factors lead to complement activation, and endothelial damages. Damaged endothelial cells release heparan sulfate which inhibits tissue factor activity and von Willed brand factor (VWVF) and causes aggregation. Finally this cascade of events cause platelets aggregation and leads to heart ischemia and cardiovascular events.
DISCUSSION:Anti-platelet therapy is an interesting premise. Anti-platelet resistance patients and bleeding as a result of using ticagrelor and prasugrel should be considered in this treatment methods. Anti-platelet drugs such as clopidogrel are prescribed in cardiovascular events. Platelets have VWF receptors and P2Y12 receptors on their surface, and thus, targeting these receptors can be useful in treatment. The active metabolites of clopidogrel bind to P2Y12R and inhibit ADP binding; thus, clopidogrel inhibits aggregation by interfering in several events as a result of the inhibition of ADP attachment to P2Y12R of the platelet. However, the polymorphisms of P2Y12 and other genes mentioned in Table 1 showed treatment resistance in anti-platelet therapy, highlighting that these SNPs can be helpful in anti-platelet therapy.
CONCLUSION: The knowledge of these SNPs may decrease the number of unwanted effects that endanger patients with cardiovascular diseases and avoids ineffective anti-platelet therapy in several patients. Clopidogrel, ticagrelor, prasugrel, and aspirin and CYP2C19 and their SNPs are very important subjects in anti-platelet therapy. To present the importance of using pharmacogenetics in anti-platelet therapy, we discuss here the association between these drugs and the SNPs for therapeutic resistance.
Habib Haybar , Zeinab Deris Zayeri . The value of using polymorphisms in anti-platelet therapy[J]. Frontiers in Biology, 2017 , 12(5) : 349 -356 . DOI: 10.1007/s11515-017-1456-0
1 |
Amarenco P, Albers G W, Denison H, Easton J D , Evans S R , Held P, Hill M D, Jonasson J, Kasner S E , Ladenvall P , Minematsu K , Molina C A , Wang Y, Wong K S L, Johnston S C, and the SOCRATES Steering Committee and Investigators (2017). Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol, 16(4): 301–310
|
2 |
Andersson H M , Siegerink B , Luken B M , Crawley J T , Algra A , Lane D A , Rosendaal F R (2012). High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women. Blood, 119(6): 1555–1560
|
3 |
Andreadou I, Iliodromitis E K, Lazou A, Görbe A , Giricz Z , Schulz R , Ferdinandy P (2017). Effect of hypercholesterolaemia on myocardial function, ischaemia-reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol, 174(12): 1555–1569
|
4 |
Angiolillo D J , Suryadevara S , Capranzano P , Bass T A (2008). Prasugrel: a novel platelet ADP P2Y12 receptor antagonist. A review on its mechanism of action and clinical development. Expert Opin Pharmacother, 9(16): 2893–2900160;
|
5 |
Armstrong P C , Hoefer T , Knowles R B , Tucker A T , Hayman M A , Ferreira P M , Chan M V , Warner T D (2017). Newly Formed Reticulated Platelets Undermine Pharmacokinetically Short-Lived Antiplatelet Therapies. Arterioscler Thromb Vasc Biol, 37(5): 949–956160;
|
6 |
Bonaca M P, Wiviott S D (2016). Prasugrel Versus Ticagrelor. Circulation, 134(21): 1613–1616
|
7 |
Bozzi L M, Mitchell B D, Lewis J P, Ryan K A, Herzog W R, O’Connell J R, Horenstein R B, Shuldiner A R, Yerges-Armstrong L M (2016). The pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: variation in platelet response to clopidogrel and aspirin. Curr Vasc Pharmacol, 14(1): 116–124160;
|
8 |
Bro-Jeppesen J, Johansson P I, Hassager C, Wanscher M , Ostrowski S R , Bjerre M , Kjaergaard J (2016). Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest. Resuscitation, 107: 71–79
|
9 |
Capodanno D, Dharmashankar K, Angiolillo D J (2010). Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist. Expert Rev Cardiovasc Ther, 8(2): 151–158
|
10 |
Castellano G, Melchiorre R, Loverre A , Ditonno P , Montinaro V , Rossini M , Divella C , Battaglia M , Lucarelli G , Annunziata G , Palazzo S , Selvaggi F P , Staffieri F , Crovace A , Daha M R , Mannesse M , van Wetering S , Paolo Schena F Grandaliano G, (2010). Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage. Am J Pathol, 176(4): 1648–1659
|
11 |
Cavallari L H , Obeng A O (2017). Genetic Determinants of P2Y12 Inhibitors and Clinical Implications. Interv Cardiol Clin, 6(1): 141–149
|
12 |
Chan N C, Eikelboom J W, Ginsberg J S, Lauw M N, Vanassche T, Weitz J I , Hirsh J (2014). Role of phenotypic and genetic testing in managing clopidogrel therapy. Blood, 124(5): 689–699 160;
|
13 |
Cohen M V, Downey J M (2014). Combined cardioprotectant and antithrombotic actions of platelet P2Y12 receptor antagonists in acute coronary syndrome: just what the doctor ordered. J Cardiovasc Pharmacol Ther, 19(2): 179–190160;
|
14 |
Cui H, Lin S, Chen X , Gao W, Li X, Zhou H , Du W, Wang S, Zhao R (2015). Correlation between SNPs in candidate genes and VerifyNow-detected platelet responsiveness to aspirin and clopidogrel treatment. Cardiovasc Drugs Ther, 29(2): 137–146
|
15 |
Daly P L, Becker R C (2014). Pharmacogenetics of antiplatelet therapy. Curr Atheroscler Rep, 16(5): 411
|
16 |
Donato R, Cannon B R, Sorci G, Riuzzi F , Hsu K, Weber D J, Geczy C L (2013). Functions of S100 proteins. Curr Mol Med, 13(1): 24–57160;
|
17 |
Farthing D E, Farthing C A, Xi L (2015). Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: from bench to point-of-care. Exp Biol Med (Maywood), 240(6): 821–831160;
|
18 |
Fontana P, Cattaneo M, Combescure C , Reny J L (2013). Tailored Thienopyridine therapy: no urgency for CYP2C19 genotyping. J Am Heart Assoc, 2(2): e000131
|
19 |
Friede K, Li J, Voora D (2017). Use of pharmacogenetic information in the treatment of cardiovascular disease. Clin Chem, 63(1): 177–185160;
|
20 |
Gajda S N, Kołtowski Ł, Tomaniak M (2014). Most recent evidence behind aggregometry and genotyping methods as platelet function testing for tailored anti-platelet treatment among PCI patients. Adv Clin Exp Med, 24(4): 687–693
|
21 |
Golukhova E Z , Ryabinina M N , Bulaeva N I , Grigorian M V , Kubova M Ch , Serebruany V L (2015). Clopidogrel response variability: impact of genetic polymorphism and platelet biomarkers for predicting adverse outcomes poststenting. Am J Ther, 22(3): 222–230
|
22 |
Gorsuch W B, Chrysanthou E, Schwaeble W J , Stahl G L (2012). The complement system in ischemia-reperfusion injuries. Immunobiology, 217(11): 1026–1033160;
|
23 |
Hasan M S, Basri H B, Hin L P, Stanslas J (2013). Genetic polymorphisms and drug interactions leading to clopidogrel resistance: why the Asian population requires special attention. Int J Neurosci, 123(3): 143–154160;
|
24 |
Hurst N L, Nooney V B, Raman B, Chirkov Y Y , De Caterina R , Horowitz J D (2013). Clopidogrel “resistance”: pre- vs post-receptor determinants. Vascul Pharmacol, 59(5-6): 152–161160;
|
25 |
Jahn K, Suchodolski K, Schäfer A , Sahlmann B , Küster U , Echtermeyer F , Calmer S , Theilmeier G , Johanning K (2017). Effect of Clopidogrel on Thrombus Formation in an Ex Vivo Parallel Plate Flow Chamber Model Cannot Be Reversed by Addition of Platelet Concentrates or vWF Concentrate. Anesth Analg, 124(4): 1091–1098160;
|
26 |
Jian L, Lu Y, Lu S , Lu C (2016). Chemical Chaperone 4-Phenylbutyric Acid Reduces Cardiac Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress. Med Sci Monit, 22: 5218–5227
|
27 |
Jiménez-Brítez G , Freixa X , Flores-Umanzor E , San Antonio R , Caixal G , Garcia J , Hernandez-Enriquez M , Andrea R , Regueiro A , Masotti M , Brugaletta S , Martin V , Sabaté M (2017). Out-of-hospital cardiac arrest and stent thrombosis: Ticagrelor versus clopidogrel in patients with primary percutaneous coronary intervention under mild therapeutic hypothermia. Resuscitation, 114: 141–145
|
28 |
Kaikita K, Ono T, Iwashita S , Nakayama N , Sato K, Horio E, Nakamura S , Tsujita K , Tayama S , Hokimoto S , Sakamoto T , Nakao K , Oshima S , Sugiyama S , Ogawa H (2014). Impact of CYP2C19 polymorphism on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing percutaneous coronary intervention. J Atheroscler Thromb, 21(1): 64–76160;
|
29 |
Kosacka M, Brzecka A, Piesiak P , Korzeniewska A , Jankowska R (2015). Soluble ligand CD40 and uric acid as markers of atheromatosis in patients with obstructive sleep apnea. Adv Exp Med Biol, 839: 55–60
|
30 |
Kubo T, Ino Y, Matsuo Y , Shiono Y , Kameyama T , Yamano T , Katayama Y , Taruya A , Nishiguchi T , Satogami K , Kashiyama K , Orii M, Kuroi A, Yamaguchi T , Tanaka A , Hozumi T , Akasaka T (2017). Reduction of in-stent thrombus immediately after percutaneous coronary intervention by pretreatment with prasugrel compared with clopidogrel: An optical coherence tomography study. J Cardiol, 69(2): 436–441160;
|
31 |
Lippi G, Franchini M, Cervellin G (2013). Diagnosis and management of ischemic heart disease. Semin Thromb Hemost, 39(2): 202–213
|
32 |
Lowe G, Rumley A (2014). The relevance of coagulation in cardiovascular disease: what do the biomarkers tell us? Thromb Haemost, 112(5): 860–867160;
|
33 |
Majumdar S, Rustagi S, Mondal S , Rijhwani V , Kaur J, Sharma P (2014). Aspirin resistance: An emerging clinical predicament is associated with single nucleotide polymorphisms. Int J Basic Appl Biol, 2(2): 63–68
|
34 |
Malhotra N, Abunassar J, Wells G A , McPherson R , Fu A, Hibbert B, Labinaz M , Le May M , Dick A, Glover C, Froeschl M , Marquis J F , Tran L, Bernick J, Chong A Y , So D Y , and the CArdiovascular Percutaneous Intervention TriAL (CAPITAL) investigators (2015). A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window. Int J Cardiol, 197: 318–325
|
35 |
Martínez-Quintana E , Tugores A (2015). Clopidogrel: A multifaceted affair. J Clin Pharmacol, 55(1): 1–9
|
36 |
Men J L, Ren J, Ma R , Wang Z X (2015). High Level of von Willebrand Factor in Non-ST Segment Elevation Myocardial Infarction Patients Predicted Cardiovascular Ischemic Events After Off-Pump Coronary Artery Bypass Surgery. Int Heart J, 56(3): 298–302 160;
|
37 |
Nadir Y (2014). Heparanase and coagulation-new insights. Rambam Maimonides Med J, 5(4): e0031160;
|
38 |
Nie X Y, Li J L, Zhang Y, Xu Y , Yang X L , Fu Y, Liang G K, Lu Y, Liu J , Shi L W (2017). Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity. J Zhejiang Univ Sci B, 18(1): 37–47
|
39 |
Olechowski B, Ashby A, Mariathas M , Khanna V , Mahmoudi M , Curzen N (2017). Is arachidonic acid stimulation really a test for the response to aspirin? Time to think again? Expert Rev Cardiovasc Ther, 15(1): 35–46
|
40 |
Ou W, He Y, Li A , Liu B, Jin L (2016). Genotype Frequencies of CYP2C19, P2Y12 and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness. Int Heart J, 57(5): 586–592
|
41 |
Perry C G, Shuldiner A R (2013). Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation? J Hum Genet, 58(6): 339–345
|
42 |
Qiu L N, Sun Y, Wang L , Han R F , Xia X S , Liu J, Li X (2015). Influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated with clopidogrel. Eur J Pharmacol, 747: 29–35
|
43 |
Rao H,
|
44 |
Ray S (2014). Clopidogrel resistance: the way forward. Indian Heart J, 66(5): 530–534
|
45 |
Razzaghi H, Tempczyk-Russell A, Haubold K , Santorico S A , Shokati T , Christians U , Churchill M E (2013). Genetic and structure-function studies of missense mutations in human endothelial lipase. PLoS One, 8(3): e55716
|
46 |
Rollini F, Franchi F, Angiolillo D J (2017). Drug-drug interactions when switching between intravenous and Oral P2Y 12 receptor inhibitors. JACC Cardiovasc Interv, 10(2): 130–132
|
47 |
Scott S A, Sangkuhl K, Gardner E E , Stein C M , Hulot J S , Johnson J A , Roden D M , Klein T E , Shuldiner A R , and the Clinical Pharmacogenetics Implementation Consortium (2011). Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther, 90(2): 328–332160;
|
48 |
Sen H M, Silan F, Silan C , Degirmenci Y , Ozisik Kamaran H I (2015). Effects of CYP2C19 and P2Y12 gene polymorphisms on clinical results of patients using clopidogrel after acute Ischemic cerebrovascular disease. Balkan J Med Genet, 17(2): 37–41
|
49 |
Sharma M Mascarenhas D A (2017). Ticagrelor associated heart block: The need for close and continued monitoring. Case Rep Cardiol, 2017; 5074891
|
50 |
Sheikh Rezaei S , Geroldinger A , Heinze G , Reichardt B , Wolzt M (2017). Clopidogrel, prasugrel, or ticagrelor use and clinical outcome in patients with acute coronary syndrome: A nationwide long-term registry analysis from 2009 to 2014. Int J Cardiol, 235: 61–66
|
51 |
Shuldiner A R ,
|
52 |
Spiel A O, Gilbert J C, Jilma B (2008). von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation, 117(11): 1449–1459
|
53 |
Stone G W, Witzenbichler B, Weisz G , Rinaldi M J , Neumann F J , Metzger D C , Henry T D , Cox D A , Duffy P L , Mazzaferri E , Gurbel P A , Xu K, Parise H, Kirtane A J , Brodie B R , Mehran R , Stuckey T D , and the ADAPT-DES Investigators (2013). Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet, 382(9892): 614–623160;
|
54 |
Sumaya W, Storey R F (2017). Ticagrelor: Effects Beyond the P2Y12 Receptor. Interv Cardiol Clin, 6(1): 49–55
|
55 |
Tekin G, Tekin Y K, Erbay A R, Turhan H, Yetkin E (2013). Serum uric acid levels are associated with atrial fibrillation in patients with ischemic heart failure. Angiology, 64(4): 300–303160;
|
56 |
Thomas M R, Lip G Y (2017). Novel Risk Markers and Risk Assessments for Cardiovascular Disease. Circ Res, 120(1): 133–149
|
57 |
Thomas M R, Storey R F (2014). Impact of aspirin dosing on the effects of P2Y12 inhibition in patients with acute coronary syndromes. J Cardiovasc Transl Res, 7(1): 19–28160;
|
58 |
Tough D F, Tak P P, Tarakhovsky A, Prinjha R K (2016). Epigenetic drug discovery: breaking through the immune barrier. Nat Rev Drug Discov, 15(12): 835–853160;
|
59 |
Ulehlova J, Slavik L, Kucerova J , Krcova V , Vaclavik J , Indrak K (2014). Genetic polymorphisms of platelet receptors in patients with acute myocardial infarction and resistance to antiplatelet therapy. Genet Test Mol Biomarkers, 18(9): 599–604160;
|
60 |
Verlinden N J , Coons J C , Iasella C J , Kane-Gill S L (2017). Triple Antithrombotic Therapy With Aspirin, P2Y12 Inhibitor, and Warfarin After Percutaneous Coronary Intervention. J Cardiovasc Pharmacol Ther, doi: 10.117711074248417698042
|
61 |
Wang K, Yuan Y, Liu X , Lau W B , Zuo L, Wang X, Ma L , Jiao K, Shang J, Wang W , Ma X, Liu H (2016). Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction. Sci Rep, 6(1): 37927160;
|
62 |
Xin Y G, Zhang H S, Li Y Z, Guan Q G, Guo L, Gao Y , Yu H J , Zhang X G , Xu F, Zhang Y L, Jia D L, Sun Y X, Qi G X, Tian W (2017). Efficacy and safety of ticagrelor versus clopidogrel with different dosage in high-risk patients with acute coronary syndrome. Int J Cardiol, 228: 275–279
|
63 |
Yang H H, Chen Y, Gao C Y (2016). Associations of P2Y12R gene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel. Cardiovasc Ther, 34(6): 460–467160;
|
64 |
Yi X, Lin J, Wang Y , Zhou Q, Wang C, Cheng W , Chi L (2016). Association of cytochrome P450 genetic variants with clopidogrel resistance and outcomes in acute ischemic stroke. J Atheroscler Thromb, 23(10): 1188–1200160;
|
65 |
Yi X, Zhou Q, Wang C , Lin J, Liu P, Fu C (2017). Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke. Eur J Clin Pharmacol, 73(4): 437–443160;
|
66 |
Yip V L M , Pirmohamed M (2013). Expanding role of pharmacogenomics in the management of cardiovascular disorders. Am J Cardiovasc Drugs, 13(3): 151–162
|
/
〈 | 〉 |