Acute Coronary Syndromes

Question 1

Causes of Plaque Rupture

Answer 1

Chemical Factors:
T-Lymphocytes – secrete gamma interferon which inhibits collagen synthesis, weakening the cap
Cells within the plaque secrete metalloproteinases which degrade the interstitial matrix

Mechanical Stress:
BP, HR, Contractility – SNS activation

Question 2

Clinical Symptoms of ACS

Answer 2

Typical Symptoms:
Sudden chest pressure
Radiation down arm (L > R)
Diaphoresis
Dyspnea
Nausea

Atypical Symptoms:
Upset stomach – gas pains
Syncope
Confusion in the elderly
Teeth/Jaw pain
Mid-Scapular back pain

Question 3

Labs, Emergent Care, and H and P of Chest Pain

Answer 3

Pain between nose and naval = ACS needs to be looked into
STEMI needs to be identified within 5-10 minutes
Vessel occlusion with STEMI = open up vessel

Initial Labs: 12 lead EKG, cardiac enzymes, electrolytes, CBC, Lipids, BUN/Cr, glucose, CXR

Emergent Care: IV access, cardiac monitoring, O2, Aspirin, and nitrates

H and P: Dx, EKG, complications, assess for reperfusion

Question 4

Treatment for ACS

Answer 4

Unstable Angina and NSTEMI: medical therapy and assess risk; if low, stress test or meds only; if high, cath lab

STEMI: medical therapy, urgent lytics or cath lab

Question 5

Medications for ACS

Answer 5

Thrombolytics, Percutaneous Intervention (PCI)
Anti-platelets
Thrombin Inhibitors
HMG-CoA Reductase Inhibitors (Statins)
Beta Blockers
ACE Inhibitors
Nitrates
Morphine- last resort

Question 6

Pathogenesis of a STEMI

Answer 6

Loss of oxygen supply leads to necrosis of viable myocardial tissue beginning within 15 minutes and occurring mainly during 30-90 minutes after acute coronary occlusion

Cath Lab vs. Thrombolytics:
PCI is preferred therapy if possible
Door to balloon time

Question 7

Types of Stents

Answer 7

1. Balloon angioplasty once placed caused dissection flap then causing a thrombus to form = weeks later a different process occurs and neo-intimal hyperplasia of vessel occurs to narrow vessel thus causing angina = not best result and have to fix again
2. Bare metal stent: stainless steel scaffolding over it to reduce elastic recoil that occurred after procedure, but thrombus still formed and have to be on anti-platelet therapy but the problem causes further promotion of the neo-intimal hyperplasia as the other stent
3. Drug eluting stents: covered with chemical + stainless steel coating to decrease growth (anti-mitotic); higher rates of patency and much more success; standard currently because vessels stay open longer and have less neo-intimal hyperplasia

Question 8

Fibrinolytics

Answer 8

Thrombolytics are derived from the same substance, t-PA, that is secreted from the endothelium
Activated plasminogen to plasmin to break down fibrin = breaks down clots

Alteplase
Retevase
Tenecteplase

Question 9

Antiplatelets

Answer 9

Aspirin (ASA); COX inhibitor

Thienopyridines: Ticlodipine, Clopidogrel (Plavix), and Prasugrel (Effient); work at ADP receptors

Direct P2Y12 Inhibitors: Ticangelor (Brilinta); work at ADP receptors

Glycoprotein 2b/3a Inhibitors: (links platelets together) this is the final pathway for inhibition of clot formation
Tirofiban (Aggrastat)
Eptifibatide (Integrelin)
Abciximab (ReoPro)

Question 10

MACE

Answer 10

New drugs must decrease MACE in order to be approved

Major Adverse Cardiovascular Events
Includes:
Cardiovascular death
Non-fatal myocardial infarction
CABG, repeat PCI
Stroke

Question 11

Thienopyridines Mechanism of Action

Answer 11

Thienopyridines: Ticlodipine, Clopidogrel (Plavix), and Prasugrel (Effient); work at ADP receptors

Binds to adenosine diphosphate (ADP) receptor, thus excludes ADP from binding to this platelet receptor

This also inhibits the subsequent ADP mediated activation of the glycoprotein 2b3a complex, which inhibits platelet aggregation.

Approved for UA, NSTEMI, STEMI

Question 12

Clopidogrel

Answer 12

Platelets are affected for the remainder of their life span.
Upon stopping, it takes approximately 5 days to see an improvement in bleeding times and platelet activation

Must stop 5 days prior to surgery

Question 13

CURE Trial

Answer 13

CURE: In those with USA/NSTEMI. Significant risk reduction in CV death, MI, CVA at 12 months with ASA + Plavix compared to ASA plus placebo. RRR of 20%, ARR of 2%

Found that patients that received a stent (PCI) had even better risk reduction

Question 14

Ticlodipine

Answer 14

Not used much anymore due to side effects:
Neutropenia (2%)
TTP (1 in 4000)
Aplastic anemia (1 in 8000)

Question 15

Prasugrel

Answer 15

Binds irreversibly to the ADP receptor on platelets for their lifespan.
Prasugrel has a greater antiplatelet effect than clopidogrel because it is metabolized more efficiently.
Results in less MACE compared to Plavix
At expense of increased bleeding rates

Also used in conjunction with aspirin
In those undergoing PCI with unstable syndrome only

Question 16

Direct P2Y12 Inhibitors

Answer 16

Ticagrelor (Brilinta); similar to prasugrel and clopidogrel

Doesn’t need to be metabolized by liver to become active component
Binds directly, faster, and more reliable
Higher risk of bleeding = always this trade off for these meds

Question 17

Glycoprotein 2b/3a Inhibitors

Answer 17

Very potent
Assess bleeding risk
Additive when used with other agents
Monitor aPTT closely when using unfractionated heparin
Caution in elderly, females, low body mass
Side Effects: bleeding, Thrombocytopenia

Always use in conjunction with aspirin and anti-thrombins
NSTEMI and unstable angina mostly

Question 18

TIMI Risk Score

Answer 18

TIMI Risk Score: predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days

Score of 3-4 = pretty high risk

Question 19

Thrombin Inhibitors

Answer 19

Heparin: accelerates activity of antithrombin
Thus inactivates factors IIa (thrombin), IXa & Xa

Enoxaparin (Low molecular weight heparin)
Inhibits Factors Xa & IIa (thrombin)

Fondaparinux: inhibits Factors Xa

Question 20

Heparin vs. Enoxaparin (LMWH)

Answer 20

Heparin:
Weight adjusted dose with variable patient response
Continuous infusion and monitor aPTT
Half life = 90 minutes
Reversal with protamine
Preferred by interventionalist

LMWH:
Weight, adjusted dose with no significant variability
Sq dosing usually bid
No monitoring required
Half life = 270 minutes
No clear reversal agent
Caution with renal disease

Question 21

Thrombin Inhibitors Side Effects

Answer 21

Bleeding

Heparin induce thrombocytopenia (HIT)
10% of patients after 5 days of therapy (less with enoxaparin)
Monitor CBC daily
Stop heparin with > 50% decrease of PLTs
Measure heparin associated platelet antibody
Start direct thrombin inhibitor
Watch for arterial thrombosis (“white clot”)

Question 22

Thrombin Inhibitors Use

Answer 22

In conjunction with ASA, thienopyridines and possibly 2b/3a inhibitors.
USA: Usually used until cardiac enzymes are negative or taken to cath lab.
NSTEMI/STEMI: Used until after intervention performed.

Question 23

Beta Blockers Contraindications

Answer 23

Caution with:
History of asthma
Bradycardia (HR 110

Question 24

ACE/ARBs

Answer 24

USA:
No clear benefit
Probably reasonable if still hypertensive with Beta blocker already on-board

NSTEMI/STEMI:
Clear mortality benefit
Started if not hypotensive on B-blocker
Goal is to start before hospital discharge

Question 25

ACE Inhibitor Side Effects

Answer 25

Contraindications:
Anaphylaxis (Angioedema)

Side Effects
Renal dysfunction
Hyperkalemia
Cough

Question 26

Nitrates

Answer 26

Endothelial-independent vasodilator
Decrease Myocardial O2 Demand

If you decrease preload then get reflex tachycardia and that causes increase O2 demand so need to give with a beta blocker

Question 27

Preventing Recurrent Events: Post-Hospitalization Suggestions

Answer 27

All Patients with ACS:
BP management
Tight control of DM
Smoking cessation
Cardiac Rehab: 36 sessions over 12 weeks
Diet, Exercise, and Psychosocial counseling

Question 28

Preventing Recurrent Events: Post-Hospitalization Medications

Answer 28

Bulk of effect of beta blockers is the first 2-3 years after infarct, so may see patients taken off these after a few years
ACE inhibitors and statins should remain indefinitely
ASA 81 mg indefinitely
Clopidogrel 75 mg for at least 12 months, or in some cases prasugrel or ticangelor
Lipid therapy to keep LDL