This document provides information on acute coronary syndromes (ACS), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). It discusses the role of atherosclerotic plaques, platelets, and the coagulation system in ACS. It also outlines the appropriate pharmacologic and non-pharmacologic treatment approaches for ACS, including antiplatelet agents, anticoagulants, fibrinolytics, and percutaneous coronary intervention (PCI). The goal of therapy is early restoration of blood flow to prevent further damage and complications from ACS.

1. Pharmacotherapy Cardiovascular Disorders
Lesson 4
Acute Coronary Syndromes
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609January, 2019

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. 1/28/2019 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.
1/28/2019 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].
1/28/2019 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 when an individual is at rest
 Severe new-onset angina
– Increasing angina > 20 minutes
– Pain may radiate to: Down the left arm, Jaw, Back, The
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.  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
30

31. 31
 Cardiac biomarkers

32. 32

33.  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.
33

34.  Goals of therapy [short term]
– Control of CV risk factors,
– Prevention of additional CV events[re-infarction, stroke, & HF]
– Improvement in quality of life.
34

35.  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
35

36.  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
36

37.  PCI considered in:
– Setting with skilled cardiologists/catheterization lab
– Cardiogenic shock,
– Contraindications to fibrinolytics,
– Continuing symptoms 12 to 24 hrs after symptom onset.
37

38.  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
38
– Irrespective of the timing of presentation;
up to 120 minutes of medical contacts

39. 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
39

40.  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]
40
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

41. 41

42.  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
42

43.  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
43

44.  Ischemia-Guided Therapy for NSTE-ACS: considered in
– Low risk score,
– Normal ECGs,
– Negative troponin tests
– Patients with extensive comorbidities
44
– Without recurrence of chest discomfort

45.  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).
45

46.  GP IIb/IIIa inhibitor + UFH: for STEMI undergoing PCI
 Morphine: for refractory pain
 β-blockers…take care!
 ACEI: within 24 hrs
 High intensity statin
46

47.  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
47
 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

48.  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.
48

49.  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
49

50.  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
50

51.  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
51

52.  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.
52

53.  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
53

54.  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)
54

55. – Stool Softeners
– Antacids: PPI
– Warfarin
– Mechanical heart valves, venous thromboembolism,
hypercoagulable disorder, and LV mural thrombus
55

56.  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.
56
So, consider them before hospital discharge accordingly

57.  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.
57* If allergy to ASA

58.  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
58

59. 59FMC: Firs medical contact

60. 60
Continued

61. 61

62. 62

63. 63

64. 64

65. 65

66.  Efficacy & safety
– Clinical signs and symptoms
– Laboratory tests and investigations
66