1. Antithrombotic Approaches in Acute Coronary Syndromes: Optimizing Benefit vs Bleeding Risks 
Mandeep Singh, MD, MPH, Deepak L. Bhatt, MD, MPH, Gregg W. Stone, MD, Charanjit S. Rihal, MD, Bernard J. Gersh, MB, ChB, DPhil, Ryan J. Lennon, MS, Jagat Narula, MD, DM, PhD, Valentin Fuster, MD 
Mayo Clinic Proceedings 
Volume 91, Issue 10, Pages (October 2016)
DOI: /j.mayocp
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2. Figure 1
Cascade of events subsequent to arterial thrombosis and activation of thromboxane A2 (TxA2) and adenosine diphosphate (ADP). These secondary agonists lead to sustained activation of glycoprotein (GP) IIb/IIIa receptors and stable platelet aggregation. During arterial thrombosis, tissue factor (TF) is exposed at the site of plaque rupture and initiates the coagulation process. Thrombin-activated factor XIIIa forms polymerized fibrin. Finally, together with aggregated platelets, the polymerized fibrin network leads to the formation of a stable, occlusive, platelet-fibrin clot and subsequent ischemic events. Vitamin K is a cofactor that promotes the biosynthesis of γ-carboxyglutamic acid residues in coagulation factor proteins, which are essential for biological activity. Anticoagulation strategies include warfarin, which acts by inhibiting the synthesis of vitamin K–dependent clotting factors, II, VII, IX, and X and the anticoagulant proteins C and S. Warfarin inhibits clotting factor synthesis by inhibition of vitamin K epoxide reductase, thereby reducing the regeneration of vitamin K1 epoxide. Other anticoagulants include direct thrombin inhibitors such as bivalirudin and dabigatran; direct Xa inhibitors such as rivaroxaban and apixaban; LMWH, heparin, and fondaparinux bind to antithrombin (AT), facilitating its inhibition of coagulation factors. Fondaparinux and LMWH preferentially inhibit Xa as compared with heparin, which more greatly inhibits IIa. Antiplatelet strategies include inhibition of platelet cyclooxygenase-1 enzyme by aspirin, resulting in the inhibition of generation of TxA2 and TxA2-induced platelet aggregation; inhibition of ADP receptor, P2Y12, by clopidogrel, prasugrel, ticagrelor, and cangrelor; inhibition of activated GPIIb/IIIa receptor by abciximab, eptifibatide, and tirofiban; and vorapaxar, which inhibits thrombin receptor protease activated receptor (PAR)-1. Factor II = prothrombin; factor IIa = thrombin; LMWH = low molecular weight heparin; TP = thromboxane A2 receptor; vWF = von Willebrand factor.
From JACC Heart Fail,5 with permission.
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3. Figure 2
Possible mechanisms linking postpercutaneous coronary intervention bleeding with increased mortality.
From J Am Coll Cardiol,13 with permission.
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4. Figure 3
Biotransformation and mode of action of P2Y12 inhibitors. Ticagrelor is rapidly absorbed in the intestine and does not require further biotransformation for activation with direct and reversible binding to P2Y12. The half-life of ticagrelor is 7 to 8 hours. The active metabolites of clopidogrel and prasugrel (prodrugs) irreversibly bind to P2Y12 for the platelet's life span. After intestinal absorption of clopidogrel, it requires 2 cytochrome P-450 (CYP)-dependent oxidation steps to generate its active compound, and prasugrel requires 1 further CYP-dependent oxidation step to generate its active compound. Most of the CYP-dependent activation occurs in the liver. Relevant CYP isoenzymes involved in the activation of both clopidogrel and prasugrel are also shown. Their activity may be affected by genetic polymorphisms.
From N Engl J Med,14 with permission.
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5. Figure 4
Choice of P2Y12 inhibitors in patients with acute coronary syndrome. All patients should be given aspirin. We prefer ticagrelor or prasugrel (if coronary anatomy is known) to clopidogrel. ACS = acute coronary syndrome; TIA = transient ischemic attack.
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6. Figure 5
Factors for physicians to consider in determining the optimal duration of DAPT after DES implantation for individual patients. ACS = acute coronary syndrome; DAPT = dual antiplatelet therapy; DES = drug-eluting stent; TIA = transient ischemic attack.
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7. Figure 6
Choice of antithrombotic therapy, including combination strategies of oral anticoagulation, aspirin, and/or clopidogrel (modified from the European recommendations). New-generation drug-eluting stent is generally preferable over bare-metal stent, particularly in patients at low bleeding risk (HAS-BLED score, 0-2). When vitamin K antagonists are used as part of triple therapy, international normalized ratio should be targeted at 2.0 to 2.5 and the time in the therapeutic range should be greater than 70%. Dual therapy with oral anticoagulation and clopidogrel may be considered in selected patients. Below are components of the CHA2DS2-VASc and HAS-BLED scores and their respective scoring systems. ACS = acute coronary syndrome; CHA2DS2-VASc = Congestive heart failure [or Left ventricular systolic dysfunction, Hypertension blood pressure consistently above 140/90 mm Hg [or treated hypertension on medication], Age ≥75 years, Diabetes mellitus, Prior Stroke or transient ischemic attack, Vascular disease [eg peripheral artery disease, myocardial infarction, aortic plaque], Age years, Sex category [female sex]; HAS-BLED = Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol; INR = international normalized ratio; TE = thromboembolism; MI = myocardial infarction; PAD = peripheral artery disease; TIA = transient ischemic attack.
CHA2DS2-VASc121ScoreHAS-BLEDScoreCongestive heart failure1Hypertension (systolic blood pressure >160 mm Hg)1Hypertension1Abnormal renal and liver function (1 point each)1 or 2Age ≥75 y2Stroke1Diabetes mellitus1Bleeding tendency/predisposition1Stroke/TIA/TE2Labile INRs (if on warfarin)1Vascular disease (prior MI, PAD, or aortic plaque)1Elderly (eg, age >65 y)1Drugs or alcohol (1 point each)1 or 2Aged y1Sex category (ie, female sex)1Maximum score9Maximum score9INR = international normalized ratio.
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