Topic Discussion During Critical Care Rotation

1. 1
IHD
ACS
UA NSTEMI STEMI
SA
Normal
Build up:
Extracellular
lipid
Fibrofatty
stage
Procoagulant
Disruption
cap
Thrombus
Background and Epidemiology
Pathophysiology
Acute Coronary Syndromes: The Inpatient Edition
Anna Sandler
PharmD Candidate, 2023
 Coronary artery disease
(CAD) remains the leading
cause of death in the USA
o > 18.2 million adults
affected
o >365, 000
death/year
 2014 Median age at
presentation: 68 y/o
 Bottom line: ACS is due to an abrupt
reduction in coronary blood flow
o Reduction in blood supply to
the heart
 Culprit: Atherosclerosis disease
(ASCVD)
o Note other causes can be at
play1
 Reduction in blood flow
ischemia/infarction
IHD: Ischemic Heart Disease; NSTEMI: Non-ST elevated myocardial infarction; SA: Stable Angina; STEMI: ST elevated myocardial infarction; UA:
Unstable angina
1: Other causes of supply-demand mismatch vasospastic angina, coronary embolism, hypotension, hypertrophic cardiomyopathy, severe
anemia
ACS has three presentations

2. 2
ACS
UA
Normal
troponin
NSTEMI
cTn
Nomral
ST
STEMI
cTn
Elevated
ST
Diagnosis, Presentation, and Risk Stratification
Presentation
 Pressure-type chest pain occurring
at rest, last at least 10 min
 Pain can radiate
o Arms
o Neck
o Jaw
 Unexplained new-onset dyspnea
 EKG
o ST depression
o T-wave inversions
Risk factors:
Dyslipidemia
HTN
Diabetes
Smoking
 Mainstay: Cardiac Troponins (cTn)
o Troponin I and Troponin T
o Released during myocardial injury
o Increasing use of high-sensitivity troponins increasing
diagnoses
o High negative predictive value
o > 99th percentile of upper reference level required
o Diagnostic cut off: > 0.04 ng/mL2
2: Diagnostic cutoff for the Tnl-Ultra cardiac troponin assay, which was implemented in 2007
TIMI risk score: determined by the sum of the presence of 7 variables at admission; 1 point is given for each of the following
variables: ≥65 y of age; ≥3 risk factors for CAD; prior coronary stenosis ≥50%; ST deviation on ECG; ≥2 anginal events in prior 24 h;
use of aspirin in prior 7 d; and elevated cardiac biomarkers, Low risk: 0-2 points, medium: 3-4 points, high: 5-7 points
Risk assessment: Disposition and Guiding treatment
cTn: Presentation, 3-6 hours after sx onset, potentially beyond 6 hours
cTn TIMI risk score EKG
History and
symptoms

3. 3
Concept Trial Main findings
ASA ISIS-2 (1988) Reduction of vascular mortality in acute MI with ASA
Clopidogrel in
ACS
CURE (2001)
(NSTEMI)
CURRENT-OASIS
(2010)
Clopidogrel and ASA superior to ASA alone but results in higher
bleeding rates
Pre-treatment with 600 mg Plavix is is safe compared with the
conventional 300 mg dose
Prasugrel in ACS TRITON-TIMI 38
(2007)
Prasugrel had less CV mortality and non-fatal MI or non fatal
stroke than clopidogrel but more CABG-related bleeding, no
differences in all-cause mortality
Ticagrelor in
ACS
PLATO (2012) Ticagrelor had lower rates of CV death, MI or stroke, and all-
cause mortality > clopidogrel but had higher rates of bleeding
Stabilize patient for
further management
Analgesia
Nitrates
O2
A brief history lesson on antiplatelets
Treatment: Once Patients are Stabilized-Definite or Likely NSTEMI
Initial ED interventions Inpatient Management
Ischemia-guided3 Early Invasive:
PCI/CABG
ASA: Aspirin; CABG: coronary artery bypass graft; DAPR: dual anti-platelet therapy d/c: discontinue; PCI: Percutaneous Coronary
Intervention; UFH: Unfractionated heparin
3: The initial ischemia-guided strategy can also be used in those with refractory (stable) angina or angina at rest with minimal
activity despite receipt of medical therapy, as well as in those who have a very high prognostic risk such as a high TIMI score
4: elevated risk for clinical events: patients with left main disease or multivessel CAD with reduced LV function (< 0.4), prior MI, > 70
years old, ST deviation, HF, hemodynamic instability, high TIMI risk score
 Indications: Refractory
angina, elevated risk for
clinical events4
 PCI: Anti-platelets+
anticoagulants
 CABG: Non-enteric ASA +
d/c P2Y12 inhibitors
o Clopidogrel and
ticagrelor 5 days
o Prasugrel 7 days
PCI
Goal times
1) DAPT: ASA 325 mg+ Clopidogrel
600 mg or Prasugrel 60 mg or
Ticagrelor 180 mg
2) Anticoagulant: UFH, bivalirudin,
enoxaparin?
Before After
1) DAPT (at least 12
months): ASA+
clopidogrel 75 mg or
prasugrel 10 mg or
ticagrelor 90 mg BID
 Continue with medical
therapy
o ASA
o P2Y12 inhibitor
o UFH, enoxaparin or
fondaparinux: up to 8
days Long-term
DAPT for stent
thrombosis, anti-
coagulants for
coronary and
cath. thrombi
1) ASA
2) Beta Blocker
3) Statin
4) ACEi or ARB
5) ? Aldosterone
antagonist
6) DAPT?
3) GP IIb/IIa
inhibitor?

4. 4
Therapy Trial Main findings
Fondaparinux Oasis-6 (2006) Fondaparinux significantly reduced death or reinfarction at
30 days when compared to standard of care before
fibrinolysis (UFH or placebo) and did not increase bleeding
and strokes
Enoxaparin EXTRACT-TIMI 25
(2006)
Enoxaparin was superior to UFH when given at least 48
hours in patients with STEMI undergoing fibrinolysis but
was associated with an increase in major bleeding
Treatment: Once Patients are Stabilized-STEMI
Inpatient Management: Reperfusion
 Stabilize and determine type of
reperfusion therapy
o PCI versus fibrinolysis
 Determine any absolute and
relative contraindications to
fibrinolysis5
PCI Fibrinolytic Therapy
 Anti-platelet
therapies: Same as
for NSTEMI PCI
 Anti-coagulants:
same as NSTEMI
PCI
 Fibrinolytics:
o Tenecteplase
o Alteplase (tPA)
o Reteplase
 Anti-platelet therapies:
o ASA
o Clopidogrel
 Anti-coagulants(48hours-8
days)
o UFH
o Enoxaparin
o Fondaparinux
Fibrinolysis
Goal times
1) DAPT: ASA 162- 325 mg+
Clopidogrel 300 mg (≤75 y/o) or
75 mg > 75 y/o (no load)
2) Anticoagulant: UFH,
enoxaparin, fondaparinux
A brief history lesson on fibrinolytic treatments
1) DAPT: ASA +
clopidogrel for 14
more days
Before After Long-term
5: Absolute contraindications: Prior ICH, ischemic stroke within 3 mo except acute ischemic stroke within 4.5 hours, intracranial or intraspinal
surgery within 2 months, severe uncontrolled HTN, active bleeding, suspected aortic dissection; relative contraindications: hx of poorly
controlled HTN, dementia, major surgery < 3 weeks, recent internal bleeding (2-4 weeks ago), pregnancy, active peptic ulcer
Initial ED interventions
1) ASA
2) Beta Blocker
3) Statin
4) ACEi or ARB
5) ? Aldosterone
antagonist
6) DAPT?

5. 5
Therapy Recommendations, supporting evidence
ASA  Mainstay of of antiplatelet therapy
Clopidogrel  Discontinue 5 days before surgery, now no longer a preferable option in
ACS
Prasugrel  Should not be administered to paitents w/ a prior history of stroke or
TIA
Ticagrelor  ASA doses should not exceed 100 mg daily when used together with
ticagrelor
GP Inhibitors  Routine upstream use not recommended due to limited benefits on
ischemic outcomes and increased risk of bleeding
o ISAR-REACT trial
 Evidence established largely before the use of oral DAPT can be
considered as an adjunct before primary PCI with UFH for those with a
large thrombus burden or inadequate P2Y12 receptor antagonist
loading, discontinue 2-4 hours before urgent CABG. Recommendaions
applicable to those not at high risk of bleeding; trials generally excluded
high bleeding risk patients.
 Agents: Abciximab, Tirofiban, Eptifibatide
UFH  Standard of care
 Adjusted per aPTT, follow hospital protocol
 Continued for 48 hours or until PCI is performed
Bivalrudin  Used in setting of high bleeding risk or heparin-induced
thrombocytopenia
Enoxaparin  Continued for duration of hospitalization or until PCI is performed
 Add additional 0.3 mg/kg IV if > 8-12 hours since last dose or received <
2 doses before PCI
Fondaparinux  No long recommended as only anticoagulan in PCI due to higher
incidence of guiding-catheter thrombosis, add UFH or bivalrudin if PCI is
performed
Tenectaplase  Preferred agent, most fibrin specific , sinlge IV-weight based bolus
Alteplase  Not as fibrin specific as tenectaplase, given as a 90 minute weight based
infusion: Bolus 15 mg then 0.75 mg/kg for 30 min (max 50 mg), then
0.5 mg/kg (max 35 mg) over next 60 min, total dose to not exceed 100
mg
Beta blockers  Initiate PO beta blockers within first 24 hours
 Contraindications: risk of cardiogenic shock, low-output state
Statins  PROVE IT-TIMI 22 and MIRACL trials provide basis for initiating or
continuing high intensity statin therapy
ACE
inhibitors
 Start and continue indefinitely if LVEF < 0.4 and in those with HTN, DM,
or stable CKD
 ARBs for those who are ACE inhibitor intolerant
Aldosterone
antagonist
 For those receiving ACE inhibitor and beta blocker + SCr </= 2.5 mg/dL
(men) or 2 mg/dL (women) +K < 5.0 mEq/L+LVEF </= 0.4 + DM or have if
HF sx are present
Therapy table

6. 6
1. WRITING COMMITTEE MEMBERS*, O’Gara PT, Kushner FG, et al. 2013
ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A
Report of the American College of Cardiology Foundation/American Heart Association
Task Force on Practice Guidelines. Circulation. 2013;127(4).
doi:10.1161/CIR.0b013e3182742cf6
2. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the
Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report
of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines. Circulation. 2014;130(25). doi:10.1161/CIR.0000000000000134
3. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for
Coronary Artery Revascularization: A Report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. Circulation. 2022;145(3). doi:10.1161/CIR.0000000000001038
4. Gulati M, Levy PD, Mukherjee D, et al. 2021
AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and
Diagnosis of Chest Pain: A Report of the American College of Cardiology/American
Heart Association Joint Committee on Clinical Practice Guidelines. Circulation.
2021;144(22). doi:10.1161/CIR.0000000000001029
5. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of Clopidogrel to Aspirin and
Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation. N Engl J
Med. 2005;352(12):1179-1189. doi:10.1056/NEJMoa050522
6. Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes
without ST-Segment Elevation. N Engl J Med. 2001;345(7):494-502.
doi:10.1056/NEJMoa010746
7. The OASIS-6 Trial Group*. Effects of Fondaparinux on Mortality and Reinfarction in
Patients With Acute ST-Segment Elevation Myocardial Infarction: The OASIS-6
Randomized Trial. JAMA: The Journal of the American Medical Association.
2006;295(13):1519-1530. doi:10.1001/jama.295.13.joc60038
8. Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus Unfractionated Heparin
with Fibrinolysis for ST-Elevation Myocardial Infarction. N Engl J Med.
2006;354(14):1477-1488. doi:10.1056/NEJMoa060898
9. Baigent C, Collins R, Appleby P, Parish S, Sleight P, Peto R. ISIS-2: 10 year survival
among patients with suspected acute myocardial infarction in randomised comparison of
intravenous streptokinase, oral aspirin, both, or neither. BMJ. 1998;316(7141):1337-
1343. doi:10.1136/bmj.316.7141.1337
10. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus Clopidogrel in Patients
with Acute Coronary Syndromes. N Engl J Med. 2007;357(20):2001-2015.
doi:10.1056/NEJMoa0706482
11. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus Clopidogrel in Patients
with Acute Coronary Syndromes. N Engl J Med. 2007;357(20):2001-2015.
doi:10.1056/NEJMoa0706482
References

7. 7
12. Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized Trial
of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial
Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2
(Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study.
Circulation. 2005;111(16):2099-2106. doi:10.1161/01.CIR.0000161383.06692.D4
13. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus Clopidogrel in Patients with
Acute Coronary Syndromes. N Engl J Med. 2009;361(11):1045-1057.
doi:10.1056/NEJMoa0904327
Picture links:
https://floridapremiercardio.com/blog/when-a-cardiologist-may-recommend-chest-pain-treatment/
https://ccasociety.org/education/echoimage/intraoperative-imaging-coronary-arteries/
https://www.shutterstock.com/image-vector/electrocardiogram-show-st-elevation-myocardial-
infarction-1970376173