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
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
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
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
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
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
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
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
![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]](https://image.slidesharecdn.com/4-acs-200123121041/85/Acute-Coronary-Syndrome-1-320.jpg)
