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Acute Coronary syndrome

Acute Coronary syndrome

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Acute Coronary syndrome

  1. 1. Acute coronary syndrome
  2. 2. ACS:  results primarily from diminished myocardial blood flow secondary to an occlusive or partially occlusive coronary artery thrombus (imbalance between myocardial oxygen demand and supply).  ACS is classified according to electrocardiogram (ECG) changes into STEMI or NSTE-ACS (NSTEMI and UA).
  3. 3. STEMI :  A STEMI occurs when symptoms of myocardial ischemia occur in conjunction with new ST-segment elevation with subsequent release of biomarkers of myocardial necrosis, mainly troponins T or I.
  4. 4. NSTEMI  NSTEMI is limited to the subendocardial myocardium and is not as extensive as STEMI.  NSTEMI differs from UA in that ischemia is severe enough to produce myocardial necrosis resulting in the release of a detectable amount of troponins T or I, from the necrotic myocytes in the bloodstream
  5. 5.  For NSTEMI AND STEMI mortality rate is lower in patient undergoing PCI compered to patient receiving no revascularization in hospital.  In hospital mortality rate for NSETMI is lower than STEMI.  post-discharge mortality rates may be higher for NSTEMI than STEMI.
  6. 6. Ventricular Remodeling Following an Acute MI  it is characterized by left ventricular (LV) dilation and reduced pumping function of the LV, leading to HF.  ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists are all agents that slow down or reverse ventricular remodeling through inhibition of the renin–angiotensin–aldosterone system and/or through improvement in hemodynamics (decreasing preload, afterload ),also improve survival.
  7. 7. Symptoms  midline anterior anginal chest pain(Crushing , burning and heavy pressure)  It most often occurs when an individual is at rest, it last for at least 20 minutes in duration.  The chest discomfort may radiate to the shoulder, down the left arm, and to the back or to the jaw  nausea, vomiting, or shortness of breath.
  8. 8. Signs No signs are classic for ACS.  Patients with ACS may present with signs of acute decompensated HF including jugular venous distention.  Patients may also present with arrhythmias, and therefore may have tachycardia, bradycardia, or heart block.
  9. 9. Labs  Troponin I or T are measured at the time of first assessment and repeated at least once after 3 to 6 hours. And beyond 6 hours in whom normal troponin level where obtained at first with a suspension of ACS.  CBC, K, Mg, Scr, APTT, INR.  mean length of hospital stay is 3 days
  10. 10. Other Diagnostic Tests  The 12-lead ECG is the first step in management.  echocardiogram, is performed to identify patients with low LV ejection fractions (EF) (≤40%) who are at high risk of death following hospital discharge.  Selected low-risk patients may undergo early stress testing
  11. 11. TIMI Risk Score for NSTE-ACS Each one of the below point represent one point. TIMI score represent risk for death, MI, or urgent need for revascularization as follows: •Age 65 years or older •Three or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/events •Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram) •Aspirin use within the past 7 days •Two or more episodes of chest discomfort within the past 24 hours •ST-segment depression 0.5 mm or greater •Positive biochemical marker for infarction
  12. 12. High-Risk Medium-Risk Low-Risk TIMI Risk Score 5-7 points TIMI Risk Score 3-4 points TIMI Risk Score 0-2 points TIMI Risk Score Mortality, MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 Days 0/1 4.7% 2 8.3% 3 13.2% 4 19.9% 5 26.2% 6/7 40.9%
  13. 13. General Approach to Treatment  oxygen administration (if oxygen saturation is low, less than 90%).  continuous multi-lead ST-segment monitoring for arrhythmias and ischemia.  frequent measurement of vital signs.  bed rest for 12 hours in hemodynamically stable patients.  and pain relief
  14. 14. in case of non PCI:  clopidogril is the preferred P2Y12 inhibitor when fibrinolytic therapy is utilized, No loading dose recommended if age older than 75 years.  IV UFH: given for up to 48 hours or until revascularization.  Enoxaparin or fondaparinux: given for the duration of hospitalization, up to 8 days or until revascularization.  In patients with STEMI receiving a fibrinolytic or who do not receive reperfusion therapy, administer clopidogrel for at least 14 days and ideally up to 1 year
  15. 15. PCI (SETMI): PCI lower risk of hemorrhage compered to fibrinolysis.  PCI open 90% of the occluded vessel while fibrinolysis open 60%. PCI: those with contraindications to fibrinolytics, and those with continuing symptoms 12 to 24 hours after symptom onset. For STEMI, one important measure is the time from first medical contact to the time the occluded artery is opened with PCI. This first medical contact-to-primary PCI time should be equal to or less than 90 minutes primary PCI can be performed within the first 120 minutes of medical contact
  16. 16. Treatment of STEMI (fibrinolytic) :  Administration of a fibrinolytic agent is indicated in patients with STEMI who present within 12 hours of the onset of chest discomfort to a hospital not capable of primary PCI.  not able to be transferred and undergo primary PCI within 120 minutes of medical contact.  The mortality benefit of fibrinolysis is highest with early administration and diminishes after 12 hours. The use of fibrinolytics between 12 and 24 hours after symptom onset should be limited to patients with ongoing ischemia.  In patients who have a contraindication to fibrinolytics and PCI, or who do not have access to a facility that can perform PCI, treatment with an anticoagulant (other than UFH) for up to 8 days can be administered.  alteplase, reteplase, and tenecteplase are acceptable as first-line agents.  Streptokinase is second line.
  17. 17. Indications 1.Ischemic chest discomfort at least 20 minutes in duration but 12 hours or less since symptom onset and ST-segment elevation of at least two contiguous leads of ≥2 mm in men and ≥1.5 mm in women in leads V2-V3 and/or of ≥1 mm in other leads, or new or presumed new left bundle-branch block 2.Ongoing ischemic chest discomfort at least 20 minutes in duration 12-24 hours since symptom onset and ST-segment elevation of at least 1 mm in height in two or more contiguous leads Absolute Contraindications •Active internal bleeding (not including menses) •Previous intracranial hemorrhage at any time; ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours) •Known intracranial neoplasm •Known structural cerebral vascular lesion (eg, arteriovenous malformation) •Suspected aortic dissection •Significant closed head or facial trauma within 3 month Indications and Contraindications to Fibrinolytic Therapy for Management of ST-Segment Elevation Myocardial Infarction2
  18. 18. Aspirin:  MOA: inhibiting the synthesis of TXA2 through an irreversible inhibition of platelet cyclooxygenase-1.  Current data suggest that an initial dose of 162 to 325 mg is required  long-term therapy with doses 81-162 mg once daily orally starting hospital day 2.  Because of increased bleeding risk in patients receiving aspirin plus a P2Y12 inhibitor compared with aspirin alone, low-dose aspirin (81 mg daily) is preferred following PCI. Low-dose aspirin should be continued indefinitely.  SE:GI bleeding , dyspepsia and nausea.
  19. 19. Platelet P2Y12 Inhibitors  Clopidogrel, prasugrel, and ticagrelor are oral agents that block a subtype of the ADP receptor, the P2Y12 receptor, on platelets, preventing the binding of ADP to the receptor and subsequent expression of platelet GP IIb/IIIa receptors, reducing platelet activation and aggregation.  Clopidogrel(CYP2C19) and prasugrel(CYP 3A4 and 2B )are prodrugs, Ticagrelor is metabolized primarily by CYP3A.
  20. 20.  Prasugrel has the fewest significant drug–drug interactions of the oral P2Y12 inhibitors.  Both prasugrel and ticagrelor are more potent ADP inhibitors than clopidogrel.  Clopidogril is associated withCYP2C19 genotype, while Prasugrel and ticagrelor efficacy are not associated with it.  clopidogrel loading dose of 600 mg is recommended over administration of 300 mg for patients undergoing PCI, then 75 mg daily.  consider alternative P2Y12 receptor inhibitor if documented clopidogrel ineffectiveness (eg, poor metabolism, stent thrombosis during clopidogrel therapy) or drug–drug interactions (eg, avoid moderate and strong CYP2C19 inhibitors);  The recommended duration of P2Y12 inhibitors for a patient undergoing PCI for ACS, either STEMI or NSTE- ACS, is at least 12 months for patients receiving either a BMS or DES
  21. 21.  If CABG surgery is planned, clopidogrel and ticagrelor should be withheld preferably for 5 days, and prasugrel at least 7 days, to reduce the risk of postoperative bleeding, and restarted postoperatively, unless the need for immediate revascularization outweighs the bleeding risk. Low-dose aspirin should be continued  Do not use prasugrel in patients with active pathologic bleeding or a history of transient ischemic attack ,stroke or >75 year.  Do not use ticagrelor in patients with active pathologic bleeding or a history of intracranial hemorrhage, or in patients planned to undergo urgent CABG surgery;
  22. 22. Glycoprotein IIb/IIIa Receptor Inhibitors: abciximab, eptifibatide, or tirofiban  block the final common pathway of platelet aggregation, namely, cross-linking of platelets by fibrinogen bridges between the GP IIb and IIIa receptors on the platelet surface.  STEMI undergoing primary PCI who are treated with UFH, abciximab (IV or intracoronary administration), eptifibatide, or tirofiban may be administered.  Don’t use if fibrinolytic therapy or not doing PCI.  Don’t use in hemogenic o ischemic stroke.  The dose of tirofiban should be halved in patients with CrCl less than 30 mL/min (0.50 mL/s). No dosage adjustment for renal function is necessary for abciximab.  immune-mediated thrombocytopenia when stop treatment specially abciximab
  23. 23. Anticoagulants: UFH, enoxaparin or fondaparinux , bivalirudin  If PCI, anticoagulation is discontinued immediately following the PCI procedures.  In patients receiving an anticoagulant plus a fibrinolytic, UFH is continued for a minimum of 48 hours and if either enoxaparin or fondaparinux is selected, those agents are continued for the duration of hospitalization, up to 8 days.  In patients who do not undergo reperfusion therapy, it is reasonable to administer anticoagulant therapy for up to 48 hours for UFH or for the duration of hospitalization for enoxaparin or fondaparinux  Most common side effect of UFH and enoxaparin is heparin-induced thrombocytopenia,in this case use bivalirudin.
  24. 24.  If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin (bolus plus infusion).
  25. 25. beta blockers  β-blockers should be initiated within 24 hours of hospital admission to all patients in the absence of contraindications.  Oral beta blockers are preferred over IV in the contemporary management of ACS.  The most serious side effects of β-blocker are hypotension, acute HF, bradycardia, and heart block.  initial acute administration of β-blockers is not appropriate for patients who present with acute HF, in this case it is initiated before discharge after acute HF treatment.  β-Blockers should be continued for at least 3 years in patients with normal LV function and indefinitely in patients with LV systolic dysfunction and an LVEF less than or equal to 40% (0.40)  Patients already taking β-blockers can continue taking them.2
  26. 26. Statins  A high-intensity statin (either atorvastatin 80 mg or rosuvastatin 40 mg) should be administered to all patients without contraindications prior to PCI and continued after that.  Calcium Channel Blockers  Calcium channel blockers in the setting of STEMI are used for relief of ischemic symptoms in patients who have certain contraindications to β-blockers.  Administration of an agent that lowers HR, either diltiazem or verapamil, is preferred unless the patient has LV systolic dysfunction, bradycardia, or heart block, and then either amlodipine or felodipine is preferred.
  27. 27. nitrates One SL NTG tablet should be administered every 5 minutes for up to three doses in order to relieve myocardial ischemia.  IV NTG should then be initiated in all patients with an ACS who have persistent ischemia, HF, or uncontrolled high BP in the absence of contraindications. IV NTG should be continued for approximately 24 hours after ischemia is relieved  nitrates are tachycardia, flushing, headache, and hypotension.  Nitrate administration is contraindicated in patients who have received oral phosphodiesterase-5 inhibitors, such as sildenafil and vardenafil, within the last 24 hours, and tadalafil within the last 48 hour
  28. 28.  A- IV NTG, ticagrelol: For selected patients  B- Clopidogrel for in case of PCI :Preferred in patients at high risk for bleeding.  C- If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin bolus plus infusion.  D-SC enoxaparin:May require IV supplemental dose of enoxaparin;  E-Parogrel :Do not use if prior history of stroke/transient ischemic attack (TIA), age older than 75 years, or body weight less than or equal to 60 kg.  F- Subcut enoxaparin or UFH can be continued at a lower dose for venous thromboembolism prophylaxis following PCI.  G-fondaparinux: Requires an IV supplemental dose of UFH.
  29. 29.  All patient with NSTE-ACS should receive intranasal oxygen (if oxygen saturation is low), sublingual (SL) nitroglycerin (NTG), asoirin, a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor depending on reperfusion strategy), and anticoagulation with bivalirudin, unfractionated heparin (UFH), enoxaparin, or fondaparinux (within the first day of hospitalization, and preferably in the ED).  Oral β-blockers should be initiated within the first 24 hours in patients without cardiogenic shock.  Morphine is also administered to patients with refractory angina as described previously.  Fibrinolytic Therapy  Fibrinolytic therapy is not indicated in any patient with NSTE-ACS because increased mortality
  30. 30. Nitrates,B-blokersCalcium Channel Blockers and aspirin: Same as STEMI. Anticoagulant:  If fondaparinux is chosen for a patient initially receiving a conservative strategy who subsequently undergoes angiography and PCI, should be administered in combination with UFH .  Therapy should be continued for up to at least 48 hours for UFH until the patient is discharged from the hospital, or 8 days, whichever is shorter for either enoxaparin or fondaparinux, or until the end of PCI or angiography procedure (or up to 72 hours following PCI for bivalirudin).  For patients undergoing CABG during the same hospitalization, UFH can be continued until a few hours before CABG and LMWH should be stopped 12 hours prior to the surgery.
  31. 31.  patients with NSTE-ACS with an initial ischemia-guided approach, either clopidogrel (a 300 or 600-mg loading dose followed by 75 mg daily) or ticagrelor can be used in addition to low-dose aspirin.(ticagrelol is preferred for up to 12 month)  In PCI ticagrelor and prasugrel are preferred in patients not at high-risk of bleeding. Initiate within 1 hour following PCI
  32. 32. Glycoprotein IIb/IIIa Receptor Inhibitors  The role of GPIs in NSTE-ACS is diminishing as P2Y12 inhibitors are used earlier in therapy, and bivalirudin is selected more commonly as the anticoagulant in patients receiving an early intervention approach
  33. 33.  The most recent practice guidelines recommend an early invasive (within 24 hours) strategy with coronary angiography and revascularization with either PCI or coronary artery bypass graft (CABG) surgery for patients with NSTE-ACS at an elevated risk for death or MI, including those with a high risk score or patients with refractory angina, acute HF, other symptoms of cardiogenic shock, or arrhythmias
  34. 34. Antiplatelet Therapy Pharmacotherapy in PCI and STEMI and NSTE-ACS  All patients undergoing PCI with ACS should receive an initial dose of 162- or 325-mg of aspirin followed by a daily aspirin dose of 81 mg/day indefinitely.  A P2Y12 inhibitor antiplatelet should be administered as early as possible concomitantly with asoirin and then an oral P2Y12 agent should ideally be continued for at least 12 months following PCI  Earlier discontinuation of the P2Y12 inhibitor can be reasonable in patients at a high bleeding risk or with overt bleeding
  35. 35. drug-eluting stent (DES) and a bare metal stent (BMS)  Compared to BMS, DES reduce the rate of smooth muscle cell growth and thus stent restenosis.  DES has a high risk of developing stent thrombosis.  dual antiplatelet therapy (DAPT—aspirin plus a P2Y12 inhibitor) is indicated for at least 1 year regardless of whether or not a patient with STEMI or NSTE-ACS receives a stent.  The use of a BMS over a DES should be considered in patients who are anticipated to be nonadherent to 12 months of DAPT.
  36. 36. Secondary Prevention Following MI  goals (a) control modifiable CHD risk factors. (b) prevent the development of systolic HF; (c) prevent recurrent MI and stroke; (d) prevent death, including sudden cardiac death; and (e) prevent stent thrombosis following PCI
  37. 37.  β-blocker should be continued for at least 3 years in patients with normal LV function and indefinitely in patients with LVEF of less than or equal to 40% (0.40) or HF symptoms.46 It may be reasonable to continue a β-blocker indefinitely in patients without contraindications and with normal LVEF.  P2Y12 inhibitor should be continued for at least 12 months for patients undergoing PCI and for patients with NSTE-ACS receiving an ischemia-guided strategy of treatment. For patients with STEMI managed with fibrinolytics, clopidogrel should be continued for at least 14 days and ideally 1 year.  All patients should receive aspirin indefinitely (75-100 mg daily).  For patient not at high-risk of bleeding and who have not had overt bleeding, new guidelines indicate it is reasonable to continue dual antiplatelet therapy after 12 months.
  38. 38.  Beta blockers and calcium channel blockers as described before.  all patients should be prescribed short-acting, SL NTG or lingual NTG spray to relieve any anginal symptoms when necessary and instructed on its use.  Administration of ACE inhibitors should be continued indefinitely. Hypotension should be avoided because coronary artery filling may be compromised.
  39. 39.  Administration of ACE inhibitors, candesartan, valsartan, and losartan should be continued indefinitely. Hypotension should be avoided because coronary artery filling may be compromised. Aldosterone Antagonists  To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 7 days following MI in all patients who are already receiving an ACE inhibitor (or ARB) and a β-blocker and have an LVEF of less than or equal to 40% (0.40) and either HF symptoms or DM  patients with serum potassium concentrations greater than 5 mmol/L (5 mEq/L) or SCr greater than 2.5 mg/dL (221 μmol/L) for men, 2 mg/dL (177 μmol/L) for women should not receive an aldosterone antagonist.
  40. 40. Statins:  all patients, regardless of low-density lipoprotein cholesterol level, should ideally be prescribed a high-intensity statin. Patients aged greater than 75 years may be prescribed a moderate-intensity statin
  41. 41. But what antithrombotic therapy is best for patients with a chronic or new indication for longer-term anticoagulant therapy following hospital discharge such as atrial fibrillation, the presence of a mechanical heart valve, venous thromboembolism, or LV thrombus?  TT, when needed, should consist of warfarin (INR target 2-2.5), low-dose aspirin 81 mg orally daily, and clopidogrel 75 mg orally daily. The anticoagulant should be discontinued if possible (such as in 3-6 months post-MI in patients at risk of LV thrombus but without actual thrombi present), and then either clopidogrel or preferably aspirin, discontinued after at least 1 month in a patient with a BMS and after at least 6 months in a patient with a DES.  Concomitant use of a proton pump inhibitor is recommended in patients receiving TT undergoing PCI.

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