W11 Outline

ACUTE CORONARY SYNDROME (ACS)

Instructor Information

• Name: Rachel Kahle, PharmD

• Position: Assistant Professor of Pharmacy Practice

• Email: kohlsr@findlay.edu

• Office: 146 C

OBJECTIVES

• Distinguish between the types/definitions of Acute Coronary Syndrome (ACS)

• Relate treatment management to the types of ACS

• Summarize treatment options at each stage of management

• Practice applying knowledge of ACS management

GUIDELINES

• AHA/ACCF: Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update

• 2011 ACC/AHA/SCAI Guideline: for Coronary Artery Revascularization

• 2021 ACC/AHA/ACEP/NAEMSP/SCAI Guideline: for the Management of Patients with Acute Coronary Syndrome

• 2025 updates

OBJECTIVE I: Distinguish between the types/definitions of Acute Coronary Syndrome (ACS)

DEFINITIONS

• Acute Coronary Syndrome (ACS): "The presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia."

  • Myocardial Infarction (MI)

  • Myocardial Ischemia

  • Heart Attack

TYPES OF ACS

• Cardiac Enzymes: Elevated | - Revascularization

  • Fibrinolysis

  • Surgery |
    | NSTEMI | Partial blockage of artery | - 12-lead EKG: ST depression/T-wave inversion

  • Cardiac Enzymes: Elevated | - Revascularization

  • Medical Management |
    | Unstable Angina | Partial blockage of artery, no necrosis | - 12-lead EKG: ST depression/T-wave inversion

  • Cardiac Enzymes: No changes | - Revascularization

  • Medical Management |

  • STEMI stands for ST-elevation myocardial infarction

  • NSTEMI stands for Non-ST elevation myocardial infarction

EPIDEMIOLOGY

• 720,000/year: Americans experience new coronary events (First hospitalization for MI or CHD death)

• 335,000/year: Americans experience recurrent events

• Trends: Incidence/mortality rates are decreasing due to guideline-directed management, early use of intervention, and quicker time to intervention

• Estimated cost: $218.7 billion, making it one of the top ten most expensive conditions

Reference: Virani SS, Alonso A, Benjamin EJ, et al. Circulation. 2020;141(9):e139–e596.

ETIOLOGY

1. Atheromatous plaque rupture (90%)

2. Oxygen mismatch not due to coronary artery processes

   • Includes vasospasm, tachycardia, dissection, anemia

3. Procedural

   • e.g., PCI (Percutaneous Coronary Intervention), CABG (Coronary Artery Bypass Grafting)

Reference: Borissoff JI, Spronk HM, ten Cate H. N Engl J Med. 2011;364(18):1746–1760.

PATHOPHYSIOLOGY

Myocardial Oxygen Demand Vs. Myocardial Oxygen Supply

• Cardiac oxygen supply is affected by factors such as:

  • Heart rate

  • Oxygenation

  • Coronary blood flow

Why Oxygen Mismatch?

• The mismatch occurs due to factors such as thrombus (clot formation) and atherosclerosis leading to plaque formation, stabilization, rupture, and clot formation.

References: Rogers KC, Spinler SA. In: Chisholm-Burns MA, et al. Principles & Practice, 6e. McGraw Hill; 2022.

CLINICAL PRESENTATION

Symptoms (Typical)

• Chest Pain: Duration, character, comparison to other episodes, PMH, provoking factors

  • Duration: prolonged at rest (>20 minutes)

  • New onset that markedly limits physical activity

  • Chest tightness/pressure with radiation to jaw/arm

  • Shortness of Breath (SOB)

  • Diaphoresis

  • Weakness

  • Anxiety

  • Nausea/Vomiting (N/V)

Reference: Rogers KC, Spinler SA. In: Chisholm-Burns MA, et al. Principles & Practice, 6e. McGraw Hill; 2022.

Symptoms (Non-Cardiac)

• Commonly observed in women, diabetics, and elderly individuals:

  • Epigastric pain

  • SOB

  • Indigestion

  • Dizziness/fatigue

  • Absence of chest pain

Reference: UpToDate. Waltham (MA): UpToDate, Inc. 2022.

BIOMARKER CHANGES

• Troponin: Most sensitive marker

  • Released: 2-4 hours

  • Peak: 18-24 hours

  • Duration: 2 weeks

  • Must trend levels over time

• Other markers: CK-MB, Myoglobin

  • Necrosis indicates release of biomarkers, whereas no necrosis shows no change in biomarkers, relevant in unstable angina (UA).

COMPLICATIONS

• Cardiogenic Shock

• Heart Failure

• Valvular dysfunction

• Arrhythmias

• Stroke

• Bradycardia

• Venous thromboembolism (VTE)

OBJECTIVE 2: Relate Treatment Management to the Types of ACS

DESIRED OUTCOMES

• Early restoration of coronary blood flow

• "Time is muscle"

• Prevention of MI-associated death

• Prevention of re-occlusion

• Relief of chest discomfort

• Resolution of ST-segment changes on ECG

INITIAL MANAGEMENT (ED/911)

Note: ABC = Airway, Breathing, Circulation; Drugs from the MONA acronym include Morphine, Oxygen, Nitroglycerin, and Aspirin.
References: O’Gara PT, Kushner FG, Casey DE, et al. JACC. 2013;61(4):e78-140.

STEMI PCI

• Fibrinolysis:

  • PCI: Percutaneous Intervention

  • Target times:

  • "Door-to-primary PCI": Within 90 minutes

  • "Door-to-needle": Within 30 minutes

• Drugs:

  • Sequencing:

  • P2Y12 LD

  • Aspirin LD

  • Anticoagulant for thrombus management

• If PCI timing exceeds 120 minutes, fibrinolysis recommended

PERCUTANEOUS INTERVENTION (PCI)

• Preferred Option:

  • Lower mortality rate

  • Better success in keeping artery open

  • Less risk of adverse effects/risks

  • Uses stents released via catheter:

  • Bare Metal Stent (BMS)

  • Drug-Eluting Stent (DES)

FIBRINOLYSIS

• Chemically breaks up blockage/plaque.

• Mechanism:

  • Fibrin is the last factor in clot formation, and lysis refers to breakdown.

• Adverse effects:

  • Major bleeding risks; patients monitored closely.

• Absolute contraindications include:

  • Active bleeding or history of brain bleed

  • Suspected aortic dissection

  • Recent (within 2 months) brain/spinal surgery or ischemic stroke

• Medications include:

  • P2Y12 LD

  • Aspirin LD

  • Fibrinolytics

Reference: O'Gara PT, Kushner FG, Casey DE, et al. JACC. 2013.

CORONARY ARTERY BYPASS GRAFT (CABG)

• Definition: Open heart surgery creating alternative routes of blood flow in the heart.

• Indication: Options if stents cannot be placed during PCI.

MEDICATION MANAGEMENT

MONA: Initial Management Drug Table

References: O'Gara PT, Kushner FG, Casey DE, et al. JACC. 2013. Amsterdam EA, Wenger NK, Bindis RG, et al. JACC. 2014.

PCI MANAGEMENT

P2Y12 Loading Dose

• Common agents: Clopidogrel, Prasugrel, Ticagrelor

• Aspirin loading dose: 162-325 mg×1

• Anticoagulants include: UFH ± GP IIb/IIIa inhibitors, Tirofiban, eptifibatide, Bivalirudin.

MEDICATION TABLE (P2Y12 INHIBITORS)

CLINICAL CONSIDERATIONS FOR P2Y12 INHIBITORS

• Clopidogrel: Least potent P2Y12; longer time to achieve maximal platelet inhibition

• Ticagrelor/Prasugrel: More potent; faster onset; higher bleeding risk.

• Use of prasugrel and ticagrelor in randomized trials shows increased reduction in risk of MACE and stent thrombosis compared to Clopidogrel in patients with STEMI without concurrent fibrinolysis.

P2Y12 INHIBITOR INDICATIONS

DURATION OF DUAL ANTIPLATELET THERAPY (DAPT)

• ACS: 12 months or longer for DES/BMS

• Fibrinolysis: Minimum of 14 days

• Post-CABG: 12 months

Note: DAPT consists of a P2Y12 inhibitor (like clopidogrel or ticagrelor) and aspirin.

SUMMARY OF MEDICATION MANAGEMENT IN NSTE-ACS

• A: Antiplatelet therapy (DAPT)

• B: Beta-Blocker

• A: ACE/ARB

• S: Statin

• N: Nitroglycerin SL tablets

ALDOSTERONE ANTAGONISTS

• Use when already on ACE/ARB and:

  • EF < 40% and

  • Symptoms of Heart Failure or Diabetes Mellitus.

MONITORING POST ACS

• Relief of chest pain

• Vital signs: blood pressure, heart rate

• Continuous ECG monitoring

• Return to baseline cardiac function: may analyze LV function with echocardiograms

• Monitor for side effects of medications

DISCHARGE COUNSELING

• Patients discharged on numerous new medications:

  • Aspirin, P2Y12 inhibitors, ACEI/ARB, Beta-blockers, Spironolactone, Statins, Nitroglycerin

• Pharmacists play a crucial role in ensuring medication affordability and availability.

OBJECTIVE 3: Summarize treatment options at each stage of management

INITIAL MANAGEMENT

• M: Morphine

• O: Oxygen

• N: Nitroglycerin

• A: Aspirin

OBJECTIVE 4: Practice applying your knowledge of ACS management

CLINICAL SCENARIOS & QUIZZES

1. What to do within 10 minutes in chest pain presentation? Discuss the importance of EKG, biomarkers, and IV access.

2. Is morphine used immediately as part of the management?

3. Barriers to include P2Y12 inhibitors post-PCI.

POST QUIZ DISCUSSION

• Discuss the management of STEMI/NSTEMI.

REFERENCES

1. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–e596.

2. Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med. 2011;364(18):1746–1760.

3. Rogers KC, Spinler SA. Acute Coronary Syndromes. In: Chisholm-Burns MA, Schwinghammer TL, Malone PM, Kolesar JM, Bookstaver P, Lee KC. eds. Pharmacotherapy Principles & Practice, 6e. McGraw Hill; 2022.

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 Nov 30; 144(22): e368-454.

5. Urban P, Mehran R, Colleran R, et al. "Defining high bleeding risk in patients undergoing percutaneous coronary intervention." Circulation. 2019 Jul 16; 140(3): 240-61.