Acute Coronary Syndromes Flashcards
Causes of Plaque Rupture
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
Clinical Symptoms of ACS
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
Labs, Emergent Care, and H and P of Chest Pain
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
Treatment for ACS
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
Medications for ACS
Thrombolytics, Percutaneous Intervention (PCI) Anti-platelets Thrombin Inhibitors HMG-CoA Reductase Inhibitors (Statins) Beta Blockers ACE Inhibitors Nitrates Morphine- last resort
Pathogenesis of a STEMI
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
Types of Stents
- 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
- 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
- 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
Fibrinolytics
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
Antiplatelets
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)
MACE
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
Thienopyridines Mechanism of Action
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
Clopidogrel
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
CURE Trial
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
Ticlodipine
Not used much anymore due to side effects:
Neutropenia (2%)
TTP (1 in 4000)
Aplastic anemia (1 in 8000)
Prasugrel
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
Direct P2Y12 Inhibitors
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
Glycoprotein 2b/3a Inhibitors
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
TIMI Risk Score
TIMI Risk Score: predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
Score of 3-4 = pretty high risk
Thrombin Inhibitors
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
Heparin vs. Enoxaparin (LMWH)
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
Thrombin Inhibitors Side Effects
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”)
Thrombin Inhibitors Use
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.
Beta Blockers Contraindications
Caution with:
History of asthma
Bradycardia (HR 110
ACE/ARBs
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
