PHARM III_ Acute Coronary Syndromes (ACS) .pdf

Acute Coronary Syndromes (ACS) Myocardial infarction: Heart attack, Damage or death of an area of the heart muscle (myocardium) resulting from a blocked blood supply to that Coronary Thrombosis: formation of a clot in one of the arteries that conduct bl...

Acute Coronary Syndromes (ACS) Myocardial infarction: Heart attack, Damage or death of an area of the heart muscle (myocardium) resulting from a blocked blood supply to that Coronary Thrombosis: formation of a clot in one of the arteries that conduct blood to the heart muscle Coronary Occlusion: obstruction of coronary artery that hinders blood flow to some part of the heart muscle Hypoxia: decrease below normal levels of O2 in inspired gases, arterial blood, or tissue Ischemia: local anemia d/t mechanical obstruction (mainly arterial narrowing), of the blood supply; often marked by pain and organ dysfxn Acute Coronary Syndrome – MC Sx Describes pts w sudden imbalance bw myocardial oxygen consumption and demand Usually acute ischemia and/or infarction d/t an abrupt reduction in coronary blood flow (obstruction) ○ Usually results from coronary plaque progression, instability w/wo luminal thrombosis Eventual diagnosis determined by: symptomatic presentation ECG changes ○ ST segment changes indicate injury, possibly necrosis, bc dead tissue cannot depolarize ○ T wave inversions indicate ischemia in absence of myocardial infarction Detection of myocardial markers ○ Indication of myocardial necrosis Stable Angina ○ Predictable anginal sx ○ Ischemia but no permanent damage UA ○ (-) cardiac (±) ECG changes ○ Accelerating angina sx ○ Ischemia d/t partial occlusion but no myocardial injury biomarker NSTEMI ○ (+) cardiac enzymes (+) ECG changes ○ Ischemia d/t partial occlusion + myocardial injury biomarkers STEMI ○ (+) cardiac enzymes (+) ECG ○ Ischemia d/t complex occlusion + myocardial necrosis CP: Chest pain (angina) – in @ least 10 mins in duration ○ central/substernal compression or crushing chest pain ○ Pressure, tightness, heaviness, caramping, burning, aching sensation ○ Usually starts in retrosternal area and can radiate to one or both arms, neck, jaw Usually accompanied by: severe dyspnea, diaphoresis, N/V, Syncope/presyncope Stable Vs. ACS Angina Stable angina – predictable w activity, predictable in quality ACS angina – accelerating symptoms  ○ Rest angina – occuring @ rest and prolonged, usually >20 mins New onset severe angina Increasing angina ○ Previously dx angina that's become more frequent, longer ECG: 12 lead should be obtained within 10 mins of ED arrival ○ ST segment changes represent acute cardiac ischemia ○ Determine ST segment changes (≥ 0.05 mV) or T-wave inversion in 2 or ○ more contiguous leads Provides location and size of infarct ○ Areas of infarction do not produce electrical activity Changes in T wave are first manifestation of acute coronary occlusion (ischemia) ○ T wave inversion Followed by ST segment changes – ST segment depression, ST segment elevation ○ ST segment depression indicates lengthening of repolarization = NSTE- ACS – not fully occluded ○ ST segment elevation – indicated injury from ischemia extending from subendocardial region to subepicardial region – transmural ischemia Indicative of STEMI and fully occluded vessel LABS: ○ Cardiac troponin – preferred biomarker ○ Levels don't begin to rise until 6 hrs POST MI ○ May last up to 10-14 days ○ Creatine Kinase MB fraction (CK-MB) and myoglobin – less sensitive for myocardium and are not recommended anymore ○ BNP – can add this If no cardiac biomarkers → unstable Angina If positive cardiac biomarkers → NSTEMI  1st get sx, 12 lead ECG, cardiac biomarkers Tx Strategies: Early invasive ○ Triage patient to invasive diagnostic evaluation (i.e., coronary angiography) usually within the first 24 hours Delayed invasive ○ Within 25-74 hours Ischemia-guided (for low risk pts, angina type pts) ○ Do not go to coronary angiography right away ○ Intensify med therapy first ○ May go later d/t: failing med therapy objective evidence of ischemia based on noninvasive tests Invasive therapy – Dx angiography Percutaneous Transluminal Coronary Angioplasty (PTCA) Percutaneous Coronary Intervention (PCI) with stent placement Stent Placement High risk of clot formation until endothelium grows over the metal Bare metal stents: (uncoated) ○ Endothelium grows over metal much faster Drug-eluting stents: (coated w meds) ○ Drugs embedded into metal will slow down endothelial growth → risk of thrombosis will exist much longer Surgical interventions: Coronary bypass surgery Pharmacologic Therapy Goals of therapy Provide symptomatic relief of ischemia Prevent worsening or progression of clinical event Preserve viable myocardium  Prevent progression to death, MI, or recurrent MI Early Hospital Therapy Anti-ischemic therapy Admission for inpatient management Bed rest or chair rest with continuous ECG monitoring Oxygen Nitroglycerin SL or IV Morphine Beta Blocker ACE Inhibitor Antithrombotic therapy Anticoagulant Heparin (unfractionated heparin or low molecular weight heparin; enoxaparin), fondaparinux, or bivalirudin Antiplatelets Aspirin (classes) Thienopyridine (clopidogrel, prasugrel, ticagrelor) Glycoprotein IIb/IIIa inhibitor Initial Therapy MOANA Morphine, Oxygen, Aspirin, Nitrates, Anticoagulation (not in order of administration) Oxygen Supplemental oxygen should be administered to patients with NSTE-ACS with arterial oxygen saturation 100 mg/day only in special bleeding circumstances Severe untreated Continue in ACS patients if already taking HTN ASA Active peptic ulcer All patients with NSTE-ACS should be on Serious GI or GU ASA unless contraindicated bleeding Ticagrelor Oral, reversibly binding Side effects If cant take aspirin give this instead P2Y12 inhibitor with Bradycardia short half-life (12 hour) Dyspnea (up to 15% More rapid and of patients in first consistent onset of action week) compared to clopidogrel Drug interactions The recommended Avoid use with strong maintenance dose of ASA CYP3A inducers or to be used with ticagrelor inhibitors is 81 mg daily (do not Monitor digoxin exceed 100 mg of aspirin with ticagrelor with ticagrelor) >40mg of simvastatin or lovastatin may increase risk of statin-related ADRs Anticoagulation Heparin – protamine = anecdote Unfractionated heparin (UFH) Low molecular weight heparins (LMWHs) – Enoxaparin/lovenox Bivalirudin → typically used in STEMI Only in pts managed with early invasive strategy Used in HIT  Biggest SE = bleeding Fondaparinux → if 50% drop in platelets Used for duration of hospitalization or until PCI is performed Used in HIT Biggest SE = bleeding Class I recommendations In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy is recommended for all patients irrespective of initial treatment strategy. – ENOXAPARIN Treatment strategies Early invasive Triage patient to invasive diagnostic evaluation (ie, coronary angiography) usually within the first 24 hours Early invasive strategy ○ In pts w NSTE-ACS and high risk features (ie elevated troponin) not adequately pre-tx w clopidogrel or ticagrelor, useful to administer a GP IIB/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI ○ In patients receiving a stent (bare-metal or drug-eluting stent [DES]) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include: Clopidogrel, Prasugrel, Ticagrelor ○ GP IIB/IIIa: Abciximab, Tirofiban, Eptifibatide – for pts undergoing a PCI Ischemia-guided Do not go to coronary angiography right away Intensify medical therapy first May go later due to: Failing medical therapy Objective evidence of ischemia based on non-invasive tests Fibrinolytics Cause fibrinolysis by binding to fibrin in a thrombus and converting entrapped plasminogen to plasmin Used ONLY for STEMI Timing is critical PCI – preferred; performed within 90 minutes (optimal door-to-balloon time) or within 120 minutes of first medical contact OR if PCI is not possible Fibrinolytic therapy – recommended and should be given within 30 minutes of hospital arrival [up to 24 hours of symptom onset] Drug SE Alteplase (Activase) CONTRAINDICATIONS: Active internal bleeding Recombinant tissue plasminogen History of recent stroke activator Any prior intracranial hemorrhage (tPA, rTPA) Recent intracranial/intraspinal surgery or trauma Tenecteplase (TNKase) – typically used for stroke (last 2-3 months) Intracranial neoplasm Severe uncontrolled HTN Reteplase (Retavase) SIDE EFFECTS: Bleeding (including ICH), hypotension MONITORING: Hgb, Hct, s/sx of bleeding NOTES: Door-to-needle time should be 1 min, NTG is recommended if angina does not subside within 3-5 mins Aspirin should be continued indefinitely ○ Those tx w DAPT, 81 mg recommended daily Those w ACS managed w medical therapy alone (w/o revascularization) and tx w DAPT (dual antiplatelet therapy, P2y12 inhibitor therapy (either clopidogrel or ticagrelor) should be continued for @ least 12 months In pts w ACS tx w DAPT after BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel or ticagrelor) should be given for @ least 12 months Other meds ○ ACEi, ARBs, Aldosterone antagonists, Beta blockers, Calcium channel blockers, Statins Long Term Mgmt After ACS Aspirin Indefinitely (81 mg per day), unless contraindicated P2Y12 Inhibitor Medical Therapy Patients: Ticagrelor or Clopidogrel with aspirin 81 mg for at least 12 months PCI-Treated Patients (including any type of stent): Clopidogrel, Prasugrel or Ticagrelor with Aspirin 81 mg for at least 12 months Continuation of DAPT beyond 12 months may be considered in patients who are tolerating DAPT and are not at high risk of bleeding following coronary stent placement Nitroglycerin Indefinitely (SL tabs or spray PRN) Beta Blocker 3 years; continue indefinitely if HF or if needed for management of HTN ACE Inhibitor Indefinitely if EF < 40%, HTN, CKD or diabetes; consider for all MI patients with no contraindications Aldosterone Antagonist Indefinitely if EF ≤ 40% and either symptomatic HF or DM receiving target doses of an ACE inhibitor and beta blocker Contraindications: significant renal impairment or hyperkalemia Statin → can help stabilize plaques Patients ≤ 75 years of age, use high-intensity statin therapy Patients > 75 years of age, use moderate-intensity statin therapy Pt education Cholesterol management BP control Diabetes control Smoking cessation Lifestyle management Weight management (overweight/obesity) Pneumococcal vaccine is recommended for patients 65 years and older and high-risk patients with CV disease Annual influenza vaccine