• •Review the diagnostic workup and labs used in ACS 

• •Discuss the drugs used in the management of acute coronary syndrome 

• •Review the therapeutic pearls for the drugs use in ACS management 

• •Based on ECG and cardiac enzymes, ACS is classified into the following categories: 

• • •STE MI – ST elevation, elevated cardiac enzymes 

  • •NSTE MI – ST depression, T-wave inversion, elevated cardiac enzymes 

  • •Unstable angina – Non-specific ECG changes, normal cardiac enzymes 

ETIOLOGY

• •The initiating event of ACS events in more than 90% of patients is atheromatous plaque rupture, fissuring, or erosion of an unstable atherosclerotic plaque 

• •Stable stenosis are characteristic of stable angina 

• •Plaque rupture causes an imbalance between myocardial oxygen demand and supply 

DIAGNOSIS

• •Twelve-lead ECG 

• •Biochemical markers/cardiac enzymes/BNP or NT-pro-BNP 

• •Blood chemistry tests – potassium/magnesium/serum creatinine 

• •Baseline CBC and coagulation tests (antifactor Xa/PT/INR) 

• •Lipid profile  

TREATMENT GOALS

• •Differentiate between STE MI, NSTE MI and UA 

• •STE MI/NSTE MI 

• • •Restoration of blood flow in infarct-related artery 

  • •Prevention of death and other MI complications 

  • •Prevention of coronary artery reocclusion 

  • •Relief of ischemic chest discomfort/resolution of ECG changes 

• •UA – prevent complete occlusion and MI 

• •Long-term outcomes are control of CV risk factors, prevention of additional CV events (reinfarction, stroke, HF) and improvement in quality of life 

• •Aspirin is the preferred antiplatelet agent in the management of all ACSs 

• • •Quality performance measure for MI 

• •Aspirin irreversibly inhibits formation of thromboxane A2 through cyclooxygenase inhibition, thus inhibiting platelet aggregation 

• •At onset of chest pain, patients should be instructed to chew and swallow non-enteric for of 162-325 mg of aspirin 

  • •First dose is chewed in order to achieve high blood concentration and platelet inhibition rapidly 

• •Aspirin 75 to 162 mg once daily is recommended as daily maintenance dose 

• •Minor bleeding and GI bleeding are less frequent with lower MD 

• •Low dose aspirin preferred in patients taking ticagrelor – PLATO trial 

• •Discontinue NSAIDS/Celecoxib at time of ACS 

• •Most frequent side effects are dyspepsia and nausea 

• •Ticlopidine – Ticlid 

• •Clopidogrel – Plavix 

• •Prasugrel – Effient 

• •Ticagrelor - Brilinta 

• •Ticlopidine – Ticlid 

• •First drug used in dual antiplatelet therapy (DAPT) during infancy of coronary artert stents 

• •Dose:  250 mg twice daily 

• •Most worrisome adverse effect was neutropenia – needed to check CBC with differential every 2 weeks during the first 3 months of therapy 

• •Indication 

• • •ACS patients managed medically or with PCI 

  • •Recent MI or stroke 

  • •Peripheral arterial disease 

• •Dosing 

  • •600 mg loading dose, then 75 mg once daily 

  • •300 mg loading dose if within 24 hours of thrombolytic 

• •Metabolism 

  • •CYP2C19, CYP3A, CYP2B6, CYP1A2 

• •Current issues and controversy 

• • •“Plavix resistance” 

• • • •Genetic polymorphisms 

• • • • •Decreased effectiveness in CYP2C19 poor metabolizers 

• • • •Drug interactions 

      • •PPIs 

• • • • • •Avoid the concomitant use of clopidogrel and omeprazole 

• • •VerifyNow assay 

    • •PRU > 235 associated with increased CV events 

• •Initially approved in 2009 

• •Pharmacokinetics 

• • •Pro-drug 

  • •Onset of action 0.5 – 1 hour 

  • •Half-life 7 hours 

  • •Metabolism primarily by CYP3A4 and 2B6 

• •Side Effect  

  • •Major bleeding - Patients > 75, < 60 kg, prior TIA/stroke 

• •Indication 

• • •ACS managed with PCI 

• •Dosing 

  • •60 mg load, 10 mg once daily.  Patients < 60 kg 5 mg once daily (30 mg load) 

• •Contraindicated in patients with previous MI or stroke 

• •Not used in elective PCI 

• •Not recommended for patients > 75 years of age, unless patient is high risk (DM or prior MI) 

• •Discontinue 7 days prior to surgery 

• •Approved 2011 

• •Reversible, concentration dependent inhibitor of the P2Y12 receptor 

• •Not a prodrug 

• •Rapidly absorbed, one active metabolite (similar potency) 

• •Can crush and make into suspension 

• •Patient taking ticagrelor SHOULD NOT receive more than 81 mg per day of Aspirin 

• •Indication 

• • •ACS who are managed medically or with PCI 

• •Dosing 

  • •180 mg LD then 90 mg twice daily.  60 mg twice daily after 12 months 

• •Major Side Effects 

  • •Bleeding  

  • •Dyspnea 

  • •Bradycardia 

• •Metabolism 

  • •CYP3A4, 2B6, 2C9, 2D6 

• •Gold standard injectable anticoagulant administered to patients with STE MI to prevent re-occlusion of an infarct artery for > 50 years 

• •60 U/kg IVP (maximum of 4000 units), then 12 U/kg/h (maximum 1000 U/h) to target anti-factor Xa level  

• •May use higher doses if no GP IIb/IIIa inhibitor planned 

• •Monitor with ACT during PCI 

• •Contraindicated in HIT 

• •Bleeding most common adverse effect – can be reversed with protamine 

• •Enoxaparin (Lovenox) is the most common LMWH used 

• •Dosing:  1 mg/kg sc every 12 hours 

• • •Reduce dose in renal impairment:  1 mg/kg sc every 24 hours if CrCl < 30 mL/min 

  • •0.75 mg/kg sc every 12 hours in patients > 75 years of age 

• •Supplemental dose 0.3 mg/kg IV prior to PCI if last dose 8-12 hours prior to PCI  

• •Don’t use in active bleeding, HIT, CrCl < 15 mL/min, or if CABG surgery planned 

• •IV direct thrombin inhibitor 

• •Used in place of heparin:  0.75 mg/kg IV bolus followed by 1.75 mg/kg/h infusion.  CrCl 10-29 mL/min - ↓ infusion rate 1 mg/kg/hour 

• •May be used concomitantly with a Glycoprotein IIb/IIIa inhibitor 

• •DOC for PCI in HIT patients 

• •Bleeding is the most common adverse effect 

• •IV P2Y12 platelet inhibitor, as an adjunct to percutaneous coronary intervention (PCI) in patients who have not been pretreated with a P2Y12 inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor 

• •The recommended dosage of cangrelor is 30 mcg/kg given as an IV bolus before PCI, followed immediately by a 4 mcg/kg/min IV infusion for the duration of the procedure or for 2 hours, whichever is longer 

• • After stopping cangrelor, an oral P2Y12 inhibitor should be started to maintain platelet inhibition. Ticagrelor does not interact with cangrelor and can be given during or immediately after the cangrelor infusion 

• •Adverse effects - bleeding 

• •Three fibrinolytics have been used in STE MI – alteplase (Activase), reteplase (Retavase), and tenecteplase (TNKase) 

• •If STE MI is diagnosed, the primary goal is to open the vessel in the shortest time possible with either fibrinolysis or PCI 

• •Fibrinolytics catalyze the conversion of endogenous plasminogen to plasmin, which degrades fibrin and results in lysis of the thrombus 

• •Standard is door to needle time of < 30 minutes – the largest benefit is seen when administered early (within 12 hrs after symptom onset) 

• •Tenecteplase (TNK) 

• • •< 60 kg give 30 mg IV bolus over 5 seconds 

  • •60-69.9 kg give 35 mg IV bolus over 5 seconds 

  • •70-79.9 kg give 40 mg IV bolus over 5 seconds 

  • •80-89.9 kg give 45 mg IV bolus over 5 seconds 

  • •> 90 kg give 50 mg IV bolus over 5 seconds 

• • •Biggest adverse effect is bleeding 

• •Absolute Contraindications 

• • •Any history of intracranial hemorrhage (ICH) 

  • •Known malignant intracranial neoplasm (primary or metastatic) 

  • •Ischemic stroke within 3 months 

  • •Suspected aortic dissection 

  • •Active bleeding or bleeding diathesis (excluding menses) 

  • •Significant closed-head or facial trauma within 3 months 

  • •Major surgery within 14 days 

• •Relative Contraindications 

• • •Chronic, severe, poorly controlled hypertension 

  • •Severe uncontrolled hypertension or presentation (SBP > 180 mm Hg) 

  • •Traumatic or prolonged (> 10 min) cardiopulmonary resuscitation (CPR) 

  • •Major surgery within 14-21 days 

  • •Internal bleeding within 2-4 weeks 

  • •Noncompressible vascular punctures 

  • •Pregnancy 

  • •Active peptic ulcer 

  • •Concurrent use with oral anticoagulant (correct INR first with fresh frozen plasma) 

• •GP IIb/IIIa inhibitors block the final step of platelet aggregation 

• •Established role during PCI, to prevent early in-stent thrombosis following stent deployment 

• •Eptifibatide (Integrilin) – 180 mcg/kg IV bolus x 2 (max 22.6 mg), followed by infusion of 2 mcg/kg/min 

• •Tirofiban (Aggrastat) – 25 mcg/kg IV bolus, then 0.15 mcg/kg/min 

• •Most common side effect is bleeding 

• •Glycoprotein IIb/IIIa inhibitors could cause headache, back pain, nausea/vomiting, dizziness/lightheadness/ fainting, and pain at the injection site 

• •Before, during, and after this medicine is taken, patients should have blood tests that indicate platelet count and clotting time of the blood 

• •Target ACT of 200-250 s prior to stent deployment 

• •The vascular access sheath may be safely removed once the ACT normalizes (ACT <150 to 180). 

• •A high-intensity statin (either atorvastatin 80 mg or rosuvastatin 40 mg) should be administered to all patients prior to PCI  

• •High-intensity statin should be used regardless of prior lipid-lowering therapy to reduce the frequency of periprocedural MI following PCI 

• •SL NTG followed by IV nitroglycerin should be administered to patients with ACS and ongoing ischemia, heart failure, or uncontrolled high BP 

• •Nitrates are potent vasodilators – leads to reduction of the workload of the heart, less oxygen demand, and reduction in ischemic pain 

• •Do not use in right-sided infarcts 

• •Avoid concomitant use with concomitant PDE-5 inhibitors 

• • •Sildenafil – Viagra, Revatio 

  • •Vardenafil – Levitra, Staxyn 

  • •Tadalafil – Cialis, Adcirca 

  • •Avanafil - Stendra 

• •Nitrates should not be used in patients with hypotension or bradycardia, or if there is suspicion of right ventricular infarction 

• •Adverse Effects 

• • •Transient headache 

  • •Nausea 

  • •Vomiting 

  • •Dizziness 

  • •Flushing or face or neck 

  • •Rapid pulse 

  • •Tingling (sublingual) 

  • •Skin irritation (patch) 

• •Nitroglycerin spray (400 mcg/spray) – NitroMist 

• •Nitroglycerin capsule extended-release - Nitro-Time     2.5, 6, 9 mg 

• •Nitroglycerin rectal ointment – Rectiv 0.4% 

• •Nitroglycerin transdermal ointment – Nitro-Bid 2%, 1 g, 30 g, 60 g 

• •Nitroglycerin transdermal patch – 0.1, 0.2, 0.3, 0.4, 0.6, 0.8 mg/hr 

• •Nitroglycerin intravenous solution – 25mg/250mL, 50mg/250mL, 100mg/250mL, 200mg/500mL 

• •Nitroglycerin sublingual tablet – Nitrostat 0.3, 0.4, 0.6 mg 

• •STEMI – early reperfusion  

• •UA/NSTEMI - Early Invasive strategy - higher risk pts  

• •ASA – low dose preferred   

• •P2Y12 inhibition (ticagrelor> prasugrel > clopidogrel)  

• •GP IIb/IIIa inhibition: only selected unstable pts 

• •Anticoagulant – four choices 

Long-term:  

• •Dual antiplatelet or dual pathway inhibition 

• •SGLT2/GLP-1RA for T2DM 

• •Intensive statin Rx –> Then add ezetimibe +/- PCSK9 to LDL < 70 mg/dl  (<55 mg/dl recent MI, very high risk)  

• •Beta-blockade, ACEI 

• •Rodriguez, Fatima, and Robert A. Harrington. "Management of antithrombotic therapy after acute coronary syndromes." New England Journal of Medicine 384, no. 5 (2021): 452-460. 

• •van der Sangen, Niels MR, Rik Rozemeijer, Dean RPP Chan Pin Yin, Marco Valgimigli, Stephan Windecker, Stefan K. James, Sergio Buccheri et al. "Patient-tailored antithrombotic therapy following percutaneous coronary intervention." European heart journal 42, no. 10 (2021): 1038-1046. 

• •Writing Committee Members, Martha Gulati, Phillip D. Levy, Debabrata Mukherjee, Ezra Amsterdam, Deepak L. Bhatt, Kim K. Birtcher et al. "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines." Journal of the American College of Cardiology 78, no. 22 (2021): e187-e285.