Chapter 4: Acute coronary syndrome

1. Lesson 4
Acute Coronary Syndromes
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609January ,2020
Pharmacotherapy of Cardiovascular Disorders
Tsegaye Melaku (BPharm, MSc)
[Assistant Professor of Clinical Pharmacy]

2.  Session Tips
 Role atherosclerotic plaque/platelets/coagulation system
 Differentiate b/n STEMI & NSTEMI
 Clinical picture (specific patient).
 Appropriate non-pharmacologic (PCI) & pharmacologic therapy
 Appropriate therapeutic regimen
 Monitor & evaluate
2

3. Time is tissue!

4. 1/20/2020 4

5.  ACS: form of CHD that comprises, the most common cause of CVD death
– Results 1˚ly from diminished myocardial blood flow
» 2˚ to an occlusive or partially occlusive coronary artery
thrombus.
5

6.  ACSs: all clinical syndromes compatible with acute MI
– Result from an imbalance between MVO2 & supply
6
ACS
MI
STEMI NSTEMI
UA

7. 7

8.  STEMI: injury that transects the entire thickness of the myocardial wall
 NSTEMI: limited to the sub-endocardial myocardium
– Usually smaller and not as extensive as an STEMI.
– Differs from UA; +ve biomarkers
8

9.  Incidence: 1 million/year
 ~239,000 will die of an MI.
 > 7.6 million living persons have survived an MI.
 CHD: leading cause of premature, chronic disability.
 Leading cause of hospitalization; 6.2 million hospital discharges/yr
 1 in 6 deaths is secondary to CHD.
1/20/2020 9

10.  > $10,000 per MI hospital stay
 ~20% re-hospitalized within 1 year.
 ~60% of the costs [re-hospitalization].
 1/3 of STEMI patients die within 24 hrs of onset of ischemia
 15% of patients with UA/NSTEMI [die /re-infarction within 30 days of
hospitalization].
1/20/2020 10

11.  Atherosclerosis starts early in life
 Inflammation plays key role
 Several factors contribute to evolution:
– Endothelial dysfunction
– Formation of fatty streaks arteries
11
  Atherosclerotic
plaques

12.  Primarily rupture of atherosclerotic plaque   subsequent
platelet adherence activation aggregation   activation
of the clotting cascade
– Ultimately, a clot forms composed of fibrin & platelets
12

13.  Predominant cause: atheromatous plaque rupture, fissuring, or
erosion of an unstable atherosclerotic plaque (in 90% of case)
– Occludes < 50% of the coronary lumen prior to the
event
13

14.  X-tics of plaques that rupture
– Soft lipid rich necrotic core,
– A thin fibrous cap,
– Adventitial & perivascular inflammation,
– Intraplaque hemorrhage,
– Angiogenesis, & expansive vascular remodeling.
14
Partially/total occlusive thrombus may occur

15.  Thrombogenic contents of the plaque are exposed to blood elements.
 Exposure of collagen and tissue factor induce platelet adhesion and
activation
– Release of platelet-derived vasoactive substances (ADP)
thromboxane A2 (TXA2)
– Vasoconstriction and potentiate platelet activation.
–   cross-links platelets to each other through fibrinogen
bridges
15

16.  Extrinsic coagulation cascade pathway is activated
 Fibrinogen  Fibrin: by thrombin (FIIa)
– Fibrin stabilizes the clot
– Clot=composed of cross-linked platelets and fibrin strands
16

17. 17

18. 18

19. 19Thrombolysis in Myocardial Infarction (TIMI) risk score

20. 20
For NSTE-ACS TIMI score from
 5 to 7 high
 3 to 4 moderate
 0 to 2  low
For death, MI

21.  Cardiogenic shock: 7%
– Mortality rate-60%
– 5 to 6% of STEMI
– 2% of NSTE ACS
 HF,
 Valvular dysfunction,
 VTE ,
 Left ventricular wall rupture,
21
 Bradycardia,
 Heart block,
 Pericarditis,
 Stroke
 Ventricular& atrial tachyarrhythmias

22.  Midline anterior anginal chest pain
 Often occurring at rest
 Severe new-onset angina
– Increasing angina > 20 minutes
– Pain may radiate to: Down left arm, Jaw, Back, shoulder
 Nausea, vomiting, diaphoresis, shortness of breath
 Atypical sxs: Women, diabetics, & elderly

23.  UA: at least one of three features:
1. Occurs at rest (or with minimal exertion), usually lasting >10
minutes;
2. Severe and of new onset (i.e., within the prior 4–6 weeks);
and/or
3. Occurs with a crescendo pattern (i.e., distinctly more severe,
prolonged, or frequent than previously).
23

24. 24

26. 26

27. 27

28.  History
 Clinical symptoms
 12-Lead ECG: within 10 minutes of arrival
– Key findings
– ST-segment elevation
– ST-segment depression
– T-wave inversion
– New LBBB: STEMI
28

29. 29

30. 30

31.  Blood chemistry: K+ , Mg2+ (affect heart rhythm)
 Organ function test other than cardiac (dose adjustment)
 Baseline CBC and coagulation profile (most take antithrombotic)
 Fasting lipid panel (optional).
 Echocardiogram
 Others as appropriate
31

32. 32
 Cardiac biomarkers

33. 33

34.  Goals of therapy [short term]
– Early restoration of blood flow to prevent infarct
expansion/prevent complete occlusion
– Prevention of death and other MI complications;
– Prevention of coronary artery re-occlusion;
– Relief of ischemic chest discomfort;
– Resolution of ST-segment & T-wave changes on the ECG.
34

35.  Goals of therapy [short term]
– Control of CV risk factors,
– Prevention of additional CV events[re-infarction, stroke, & HF]
– Improvement in quality of life.
35

36.  General Approach
– Admission to hospital
– Oxygen administration (O2Sat<90% /respiratory distress)
– Continuous ECG monitoring,
– Frequent measurement of vital signs,
– Bed rest for 12 hrs
– Avoid Valsalva maneuver (stool softeners routinely),
– Pain relief
36

37. 37

38.  Two: PCI & Fibrinolysis
A. Primary PCI of infarct artery
– Within 90 minutes from time of hospital presentation.
– For STEMI who present within 12 hrs of symptom onset
– Lower mortality rate than fibrinolysis use
 >90% [by PCI] Vs. <60% [by fibrinolytics] of occluded infarct-
related coronary arteries are opened
 Lower risk of bleeding, ICH from PCI
38

39.  PCI considered in:
– Setting with skilled cardiologists/catheterization lab
– Cardiogenic shock,
– Contraindications to fibrinolytics,
– Continuing symptoms 12 to 24 hrs after symptom onset.
39

40.  The time from first medical contact to device   ≤90 minutes:
reperfusion is as short as possible.
 Transfer patients to [PCI capable settings] who develop:
– Cardiogenic shock
– Acute severe HF
– Unsuccessful fibrinolysis
– Persistent rest ischemia
40
– Irrespective of the timing of presentation;
up to 120 minutes of medical contacts

41. B. Fibrinolytic Therapy
 Indicated for
– STEMI patients arrived hospital within 12 hrs of sxs onset
– Who are initially seen at a non-PCI-capable setting
– If no cardiac catheterization lab
– Contact-to-device greater than 120 minutes
 Its effectiveness ↓ with time e.g. after 12hrs
 May be used within 12hrs- 24 hrs of presentation, in ongoing ischemia
41

42.  Recommendation: fibrinolytic agent be administered within 30 minutes
of arrival
 Fibrin-specific agent [alteplase, reteplase, or tenecteplase] preferred
over a non-fibrin-specific agent [streptokinase]
42
Don’t use fibrinolytics in NSTE-ACS
Patients with STEMI at low risk for recurrent CHD events: ASA indefinitely
– Clopidogrel for at least 14 days & up to 12 months

43. 43

44.  Early Invasive Therapy for NSTE-ACS: angiography followed by PCI or
CABG for:
– Patients elevated risk for death or MI[ high risk score]
– Refractory angina,
– Hemodynamic or electrical instability
44

45.  Tips:
– All patients undergoing PCI should receive ASA therapy
indefinitely.
– P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) +
ASA for at least 12 months following PCI
 Longer for patients with DES in PCI
45

46.  Ischemia-Guided Therapy for NSTE-ACS: considered in
– Low risk score,
– Normal ECGs,
– Negative troponin tests
– Patients with extensive comorbidities
46
– Without recurrence of chest discomfort

47.  Patient should receive within the first day of hospitalization/
preferably in the ED,
– Intranasal oxygen (if O2sat<90%),
– SL nitroglycerin  IV if still pain
– ASA,
– P2Y12 inhibitor (agent dependent on reperfusion strategy),
– Anticoagulation (agent dependent on reperfusion strategy).
47

48.  GP IIb/IIIa inhibitor + UFH: for STEMI undergoing PCI
 Morphine: for refractory pain
 β-blockers…take care!
 ACEI: within 24 hrs
 High intensity statin
48

49.  Nitrates
– Venous & arterial vasodilation
– ↓ MVO2, preload, BP
– Relieves vasospasm
– ↑myocardial blood flow &
oxygenation.
– 0.3-0.5 mg SL q 5minx 3 doses
– IV NTG: in persistent ischemia, HF,
uncontrolled BP
 Continued until
revascularization or for ~ 24
hrs
– S/E: tachycardia, flushing, headache,
hypotension
49
 Aspirin (ASA)
– Cornerstone of early Rx for all
ACS
– Reduces mortality,
– Its effects are additive to
fibrinolysis alone.
– In PCI, prevents acute thrombotic
occlusion during the procedure.
– Reduces the risk of stent
thrombosis.
– Reduces risk of death/MI ~50%
– LD: 162-325mg; MD: 81-162mg
– Continued indefinitely
– DC other NSAIDS

50.  Platelet P2Y12 Inhibitors
– Clopidogrel, prasugrel, ticagrelor
– Block P2Y12 receptor on ADP receptor
– Added to ASA in ACS
– Clopidogrel: LD: 300 mg (600mg in PCI); MD: 75mg QD
– Prasugrel: LD: 60-mg; MD: 10 mg QD
– Ticagrelor: LD:180-mg; MD: 90 mg Bid
– Omit LD > 75 yrs old
– In STEMI who received fibrinolysis:
– Early clopidogrel 75 mg QD ~28days(mean: 14 days) ~ 1yr
– In patients who received PCI, but not Clopidogrel: initiate within 1hr of
PCI, if no C/I.
50

51.  Glycoprotein IIb/IIIa Receptor Inhibitors
– Abciximab, eptifibatide, tirofiban
– Routine use not recommended
– Not routinely recommended if ischemia-guided approach used
[bleeding >benefit]
– But, recurrent ischemia/HF/arrhythmias after initial Rx
– Should not be administered in STEMI who will not be undergoing PCI.
– Their role diminishing in NSTE-ACS
– Considered in:
– Those not adequately treated with a P2Y12 receptor
antagonist or
– Those with a large thrombus burden
51

52.  Anticoagulants
– Added to DAPT regardless of ACS type or initial treatment strategy
– STEMI undergoing primary PCI: UFH or bivalirudin
– STEMI with fibrinolytic therapy: UFH/enoxaparin/ fondaparinux
– DC after PCI unless a compelling reason to continue exists
– For minimum of 48hrs [for UFH]
– For duration of hospitalization (for enoxaparin &fondaparinux) ~ 8 days
– In PCI
– Don’t used Fondaparinux as sole anticoagulant; add heparin
52

53.  In NSTE-ACS patients in whom an initial ischemia-guided strategy is
planned:
– Enoxaparin, UFH, or low-dose fondaparinux is recommended.
– If planned PCI with fondaparinux, add heparin
 UFH is preferred
– Following angiography in patients proceeding to CABG [short duration]
– CrCl < 30 mL/min: avoid Fondaparinux
– In dialysis patients; as enoxaparin should be avoided
– If HIT occured: Bivalirudin
53

54.  β-Blockers
– ↓ MVO2, HR, BP, myocardial contractility
– ↓ HR ventricular filling & coronary artery perfusion
– ↓risk for recurrent ischemia, infarct size, risk of re-infarction, &
occurrence of ventricular arrhythmias
– Oral β-blockers in early ACS
– IV: early risk of cardiogenic shock
– Continue at least for 3 years in patients with normal LVF
– S/E: acute HF, bradycardia, heart block.
54

55.  Calcium Channel Blockers
– Relief of continued ischemia despite β-blocker & nitrate therapy
– Need for BP lowering (i.e, amlodipine),
– In patients with contraindications to β-blockers
– Little benefit on clinical outcomes beyond symptom relief [esp.↓LVEF]
– Avoid in the acute management of ACS
55

56.  Other therapies
– Oral ACEI:
– Initiate within 24 hours
– Should be continued indefinitely.
– Statin [high intensity]
– Prior to PCI reduce the risk of peri-procedural MI
– ↓ risk of CV death/recurrent MI/stroke/need for
revascularization
– <75 Yrs old: Atorvastatin: 40–80 mg QD; rosuvastatin 20–40
mg QD
– > 75 Yrs old: atorvastatin 10–20 mg; pravastatin 40–80 mg;
simvastatin 20–40 mg)
56

57. – Stool Softeners
– Antacids: PPI
– Warfarin
– Mechanical heart valves, venous thromboembolism,
hypercoagulable disorder, and LV mural thrombus
57

58.  Long-term goals following ACS :
– Control modifiable CHD risk factors;
– Prevent the development of HF;
– Prevent new or recurrent MI and stroke;
– Prevent death, including sudden cardiac death;
– Prevent stent thrombosis following PCI.
58
So, consider them before hospital discharge accordingly

59.  Recommendation
– Treat & control of modifiable risk factors [HTN, dyslipidemia,
obesity, smoking, & DM
– ASA/clopidogrel*, β-blocker, ACEI, statin: may be indefinitely
– P2Y12 inhibitor: at least 12 months for in PCI & for patients with
NSTE-ACS receiving an ischemia guided treatment strategy
– For medically treated patients: 14 days- 1yr for STEMI; 1yr for NSTE-ACS
– Clopidogrel: at least 14 days and up to 1 year in patients with
STEMI receiving thrombolytics.
– ARB & aldosterone antagonist: selected patients.
59* If allergy to ASA

60.  Aldosterone Antagonists shouldn’t be used/hold
– In hyperkalemia [k+> 5.0 mEq/L]
– SCr ≥2.5 mg/dL for men or ≥2.0 mg/dL for women
– CrCl ≤30 mL/min
60

61. 61FMC: Firs medical contact

62. 62
Continued

63. 63

64. 64

65. 65

66. 66

67. 67

68.  Efficacy & safety
– Clinical signs and symptoms
– Laboratory tests and investigations
68