Therapeutics III Dr.

Birtcher 1/20/11

ACS (part 1)

ACUTE CORONARY SYNDROME (ACS) part I

Objectives Discuss pathophysiology & presentation of acute coronary syndromes (ACS) o unstable angina (USA) o non-ST segment elevation myocardial infarction (NSTEMI) o ST segment elevation myocardial infarction (STEMI) Recommend short-term & long-term treatment based on patient characteristics & presentation State strategies for improving compliance Introduction of ACS Synonyms for Coronary Artery Disease (CAD) o Ischemic heart disease (IHD) o Coronary heart disease (CHD) Common manifestations o Chronic stable angina o Coronary artery vasospasm (variant or Prinzmetals angina) o Acute coronary syndrome i. USA, NSTEMI, STEMI Statistics CAD is the leading cause of death in the US o AMI is most common presentation 25 35% of those having AMI die before medical attention is possible o very important to activate the EMS quickly bc TIME IS MUSCLE Hospital Admissions for ACS: Unstable Angina/NSTEMI* vs STEMI** Trying to show that there are a lot of patient that present with diagnosis in the hospital o and most of the patients will be in the unstable angina (UA)/ NSTEMI diagnosis NSTEMI = also known as non-Q wave MI STEMI = also known as Q wave MI

Vascular Disease: A generalized and progressive process Keep in mind that the progression of atherosclerosis is over time

In this particular scenario, we have that fibrous cap comes off, a thrombus has formed, and in this situation, were talking about the unstable angina and MI

Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Common underlying thrombotic disease process Another way of depicting the information in the other slide

Keep in mind that a lot of times, patients who have clots form can be in the coronary arteries, carotid, or peripheral arteries as well The pathophysiology is the same, you get plaque rupture, and bc you have that plaque rupture, it starts the bodys process of trying to heal it so you get platelet adhesion, activation, aggregation. Bottom line is you get a plaque, or thrombus, forming that may occlude completely or partially a vesseland that leads to all kinds of problems, a heart attack if the thrombus is the coronary, a stroke if it is in the carotid, etc.

ACS Prehospital, EMS, Community Prehospital deaths related to arrhythmias usually ventricular fibrillation (VF) o Most occur w/ in 1st hour i. If you find someone down, call 911! Dont start the CPR process if you are by yourself. o Account for 50% AMI mortality o In hospital deaths d/t VF are relatively uncommon o Mortality related to infarct size i. Goal: limit infarct, limit mortality 1. Time is muscle! If you can activate the system quickly, you can actually decrease the potential infarct size. EMS care is essential to o Ensure rapid triage & transport to definitive care o Prevent or treat sudden cardiac death Goals of treatment o Prevent delay in activation of EMS (call 911) o Recognize & treat sudden death arrhythmias i. 1st responder & early defibrillation o EMS triage, rapid transport, & prearrival notification of receiving hospital o Limit infarct size w/ appropriate therapy o Preserve LV function o TIME IS MUSCLE!!! Community requirements o Educate pts, community about signs of AMI i. Need to phone 911 w/out delay ii. Time is brain. Respond very quickly! It is important to get help early. iii. A lot of treatment options cannot be used if we do not get help early. o Train & equip 1st responders for arrival w/in 5 minutes & rapid defibrillation i. 1st hour = highest risk for VF/VT o Develop protocols for EMS triage of pts w/ ischemic type CP
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

i. Prehospital EKG, NTG, ASA, other drugs (thrombolytics-?) Designate hospitals w/ 24 hr emergency CV care & those capable of rapid coronary intervention (PCI) i. They are focusing on STEMI so people get the best care early on

ACS Presentation with Ischemic Type Chest Pain Immediate assessment ( < 10 min)all of this is happening at the same time. o Measure vital signs (automatic/standard BP cuff) o Measure O2 saturation o Obtain IV access o Obtain 12 lead EKG (physician views) o Perform brief, targeted history; focus on eligibility for thrombolytic therapy o Obtain initial cardiac marker levels o Evaluate initial electrolytes & coagulation studies o Request, review portable chest X-ray (<30 minutes) Immediate general treatment o O2 at 4 L/min o ASA (chew and swallow) o NTG SL or spray i. Tell pt to use 1 tab under the tongue if they dont get relieve or the pain gets worse, call 911 ii. Continue to take the NTG every 5 minutes until paramedics iii. No maximum with NTG - once they get to hospital, they may be given NTG drip o Morphine IV (If pain is not relieved by NTG) o Memory aid: MONA greets all patients with chest pain i. (Morphine, Oxygen, NTG, ASA) 1. If ischemic type of pain, want MONA on board ACS MONA Aspirin o Take orally or chew 162 325 mg o Avoid enteric coated products (want immediate OOA) o infarct extension, reinfarction, mortality o Precautions i. Active PUD (if have PUD, then use rectal suppositories), allergy, bleeding disorder, severe hepatic disease o Continue indefinitely Nitroglycerin (given either in EMS unit or at hospital) o SL is 1st line to relieve symptoms of acute ischemia i. 0.4 mg SL q 5 minutes ii. Cannot overdose on tablets? o IV drip for ongoing/recurrent pain despite SL NTG & Beta- blocker i. 10 mcg/min IV; increase by 10 mcg/min q 3 5 minutes 1. most patients will be able to get oral therapy of BB ii. Titrate to pain relief, resolution of EKG abnormalities, or SBP 90 mm Hg 1. IV drip will be a much higher dose than tablets iii. Usually given 24 48 hrs (1-2 days) o Does not improve clinical outcomes i. Reason beta-blockers take precedence ii. NTG is the 3rd line agent in Angina treatment, but it helps with symptoms o SE i. Hypotension ii. HA iii. Reflex tachycardia (w/out beta-blocker) o Contraindications i. SBP < 90 mm Hg, HR < 50 or > 100
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

ii. Right ventricular infarction iii. Sildenafil, vardenafil w/ in 24 hrs; tadalafil w/in 48 hrs Morphine sulfate o Give IV for i. pain not relieved w/ NTG ii. acute pulmonary edema iii. severe agitation o MOA i. Decreases MVO2 by decreasing preload, afterload, HR ii. Potent analgesic & anxiolytic o Dose i. 1 5 mg IV q 5 30 (low dose) o SE i. Hypotension 1. Low doses do not really affect hypotension ii. Respiratory depression (rare prb) 1. Very low doses do not affect pulmonary patients and also potent anxiolytic so we do not want to withold from patient iii. Urinary retention NSAIDS o Discontinue NSAIDS (except ASA) at the time pt presents w/ ACS i. Includes non-selective & COX-2 selective agents ii. NSAIDs increase risk of mortality, reinfarction, HTN, HF, myocardial rupture

ACS Presentation with Ischemic Type Chest Pain For out of hospital presentation o EMS personnel can perform i. Immediate assessment & treatment (MONA) ii. Initial EKG iii. Review for thrombolytic therapy indications & contraindications 1. NOTE: USA/NSTEMI not eligible for thrombolytics 2. Thrombolytic therapy is used for STEMI ONLY iv. Some EMS may give thrombolytics in the field 1. Thrombolytic therapy puts the pt at risk for bleeding 2. Thrombolytics therapy is used usually when the pt cannot be taken to a place with a cath lab; but cath lab is the more common practice these days 3. Thrombolytic therapy may be the option for some patientspatients in rural areas a. Cant go to hospitals (cath), so will be on thrombolytics, but risk of bleeding (need to evaluate CI first) Assess 12 lead EKG o ST elevation or new left bundle branch block (LBBB) heart attack i. Strongly suspicious of injury ii. ST segment AMI (STEMI) iii. Assess for reperfusion candidacy Thrombolytics vs. PCI o ST depression or dynamic T wave inversion i. Strongly suspicious of ischemia ii. High risk unstable angina/non-ST segment AMI (USA/NSTEMI)

Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

- on the test, she will tell us whether the evaluation is STEMI or NSTEMI

Non-diagnostic EKG: absence of changes in ST segment or T waves i. Intermediate/low-risk unstable angina ii. Further assessment usually needed 1. Repeat/continuous EKG, serial cardiac markers, myocardial imaging, 2D echocardiogram Other conditions that may present like AMI (When is a MI not a MI?) i. Aortic dissection ii. Pericarditis/myocarditis iii. Pulmonary embolism

*ACS Cardiac Markers (look for a change) Pathophysiology o Blocked blood flow to myocardium o Cellular (myocytes) ischemia o Injury o Death o Necrosis Differentiate between AMI & USA o No diagnostic elevations of cardiac markers w/ USA Measured at least 3 times o In the ER, after 12 hrs, and after 24 hrs looking for a change Provide risk stratification & prognostic info on how patient will do as far as complications in the hospital o high, early levels predict more complications during hospitalization ACS Cardiac Markers CK-MB is measured o Appears (elevates) w/in 6 hrs of AMI o Returns to normal within 48 hrs o To diagnosis AMI, need 2 abnormal CK MB results > above MI decision limit set by lab i. Abnormal levels are set by the lab at each individual hospital Cardiac Troponin is measuredmost commonly used o Cardiac specific o Not normally detected i. Normally do not have a level of troponin that can be detected o Detect minimal myocardial damage i. Will differentiate NSTEMI vs. USA o Appears w/in 6 hrs of AMI
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Remains elevated up to 10 days To diagnosis AMI, need 1 abnormal troponin result > above MI decision limit set by lab

ACS Treatment

We have the initial treatment, so we have MONA greeting everybody. Weve got the EKG, the cardiac markers, and were going to discontinue the NSAIDs. Base on the cardiac markers and EKG, we have to decide if we have a patient with a heart attack or not. o STEMI + positive cardiac markers (both) STEMI (acute myocardial infarction) o ST segment depression + positive cardiac markers NSTEMI o ST segment depression + negative cardiac markers + patient w. crushing chest pain unstable angina Key thing to remember is when you have a patient with a heart attack, there is a clot there. Were going to be very aggressive with our antiplatelet therapy, anticoagulants. Were going to be hitting the clotting cascade multiple ways so there is going to be a lot of heavy duty treatment on board. o (Anticoagulants in all = STEMI, USA, NSTEMI) UA/NSTEMI o Clopidogrel*, anticoagulant (planned PCI = bolus dose of heparin + IV heparin infusion for a couple days; alternative is LMWH), GP IIb-IIIa (b/c of heart attack) o Reperfusion therapy Percutaneous coronary intervention or bypass surgery or they may be medically managed depending on whats going on after you take them to the cath lab o Long term: were going to do ABCDEF STEM o Will triage to either reperfusion via PCI or thrombolytic Refer back to notes about prasugrelspecific indication, when you would use it and when not use it (instead of Plavix)

USA/NSTEMI Definition o USA: acute ischemic syndrome characterized by 1 of these: i. New onset (< 2 months) exertional angina of Class III or IV 1. Limiting activity or pain at rest = class 3 or 4 ii. Acceleration or worsening of angina to at least Class III over a short time period iii. Symptoms of angina at rest, usually > 20 minutes 1. Symptoms lasting for a longer time o NSTEMI: acute ischemic syndrome characterized by: i. Elevation of cardiac markers AND ii. ST segment depression on EKG in presence of other clinical & EKG features characteristic of angina 1. For it to be a heart attack, you have to have the enzymes present at an elevated level
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Clinical presentation o USA i. No elevation in cardiac markers ii. Absent or transient EKG changes o NSTEMI i. Elevated cardiac markers (troponins, CK-MB) ii. ST segment depression, T wave inversion o USA & NSTEMI may be indistinguishable on presentation i. Some tx overlap tk to CATH or not Pathophysiology o Most common i. Plaque rupture w/ non-occlusive thrombus formation 1. So it is not completely blocking the vessel Treatment goals o Prevent MI/death o Relieve symptoms & reverse myocardial ischemia o Modify risk factors Note! o There is no role for thrombolytics w/out ST-segment elevation or new left bundle branch block (increase death, MI, bleeding) i. Thrombolytics are reserved for STEMI only***

USA/NSTEMI Select management strategy Early invasive (angiography) for high risk patients o Recurrent angina/ischemia at rest or w/ low level activity o Elevated troponin Means they have NSTEMI These patients are considered high risk and they are going to go the cath lab, and get angiography o s/s HR or new/worsening mitral regurgitation o Hemodynamic instability o Sustained ventricular tachycardia o PCI w/in 6 months o Prior CAB o High risk score (TIMI, GRACE) for USA o Reduced LVEF (< 40%) Conservative (meds only, no angiography)when patients are not considered high-risk o Low risk score (TIMI, GRACE) Dont have to know scoring system, just know that it exists Pts with low risk score, would be manage conservatively If not, then go to cath lab o Patient or physician preference in absence of high-risk features Patients with unstable angina, usually do conservative tx (have risk scoring on the pts) USA/NSTEMI Initial Invasive (Angiography) Strategy Anticoagulant o Unfractionated heparin preferred o Enoxaparin preferred o Fondaparinux o Bivalirudin Clopidogrel 600 mg loading dose, then 75 mg daily o Ticlopidine (older agent) Alternative to clopidogrel
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

500 mg loading dose, then 250 mg PO BID has a lot of blood dyscrasia SE associated with it so pts need to get frequent monitoring after they start on this therapy not used often IV antiplatelet agent o GP IIb IIIa inhibitor Especially with delay to angiography, high risk features, early recurrent ischemic discomfort Diagnostic angiography o Currently: pt will be on ASA, Anticoagulants (Heparin, Plavix, GP2b/3a inhibitor) because the clot is there And then send to angiography to see whats going on

USA/NSTEMI Initial Conservative Strategy Anticoagulant o Unfractionated heparin (UFH) 3rd choice For 48 hrs o Enoxaparin 2nd choice For 8 days or duration of hospitalization o Fondaparinux 1st choice (**different) b/c Anticoagulation with Fondaparinux is not as complete as UFH or LMWH (Enox) so use in a less of an emergency type situation but if the pt ends up going to the CATH lab, then will be on unfractionated Heparin or Enoxaprin Clopidogrel 300 mg loading dose, then 75 mg daily (lower dose here b/c less of an ER) o Ticlopidine Alternative to clopidogrel 500 mg loading dose, then 250 mg PO BID IV antiplatelet agent o GP IIb IIIa inhibitor Consider eptifibitide or tirofiban Use will depend on patient presentation (may/may not use it) USA/NSTEMI Initial Medical Treatment o Anticoagulants use one; will use in combination with other drugs that will thin the blood Unfractionated heparin (UFH) Low-molecular weight heparin (LMWH) Fondaparinux Bivalirudin Goal: prevent further thrombus formation Add to ASA + clopidogrel + GP IIb-IIIa inhibitor to thin out the blood o Heparins *dont have to know dose, but know that it is based on weight and the pt will be on for 48 hr UFH Loading dose 60 units/kg (max 4000 units) then 12 units/kg/hr (max 1000 units/hr) titrated to aPTT 1.5 2.0 x (about 50 70 sec) use for 48 hrs max, then switch to another agent Contraindications Hypersensitivity to heparin/pork (pork products) Heparin-induced thrombocytopenia LMWH Enoxaparin 30 mg IV bolus, 1 mg/kg SQ every 12 hours
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Donhave to know dose, but notice that pt gets an IV bolus dose and then SQ therapy which is different Most commonly used o >75 years old; no bolus, 1 mg/kg SQ q 24 hr o PCI: Give 0.3 mg/kg IV bolus if > 8hr since last dose o PCI: Give 0.5 0.75 mg/kg if no previous enoxaparin dose Dalteparin 120 IU/kg SQ every 12 hours o Switch to UFH during PCI Precaution adjust doses for CrCl <30 mL/min Heparins (LMWH) are excreted renally so caution in low CrCl o In this particular situation (low CrCL), wed prefer to use the unfractionated heparin bc it is easier to make adjustments and decrease the risk of bleeding Contraindications Hypersensitivity to heparin/pork Heparin-induced thrombocytopenia

Fondaparinux Pentasaccharide sequence of heparin that binds with antithrombin III to inactivate factor Xa 2.5 mg SQ daily May be preferred for patients treated conservatively (no angiography) If used prior to PCI, must give heparin IV bolus dose (50 60 units) to avoid catheter thrombus formation Bc fondaparinuxs anticoagulation is not as complete o If were on Fondaparinux, and now decided to go to cath lab, then would need a Heparin dose, if not a thrombus can form on the catheter May cause thrombocytopenia Lacks in vitro cross-reactivity with heparin-induced thrombocytopenia antibodies Risk of major bleeding increased in the elderly Contraindicated if CrCl < 30 mL/minute due to increased bleeding risk Bivalirudin Direct thrombin inhibitor (DTI) Reserved for pts with heparin induced thrombocytopenia - This is its role in therapy Loading dose 0.1 mg/kg, then 0.25 mg/kg/hr infusion Give additional bolus (0.5 0.75 mg/kg) + increase infusion rate (1.75 mg/kg/hr) during PCI

IV antiplatelet therapy - GP IIb IIIa inhibitors MOA: Inhibits the integrin GP IIb/IIIa receptor in the membrane of the platelet Blocks final common pathway of platelet aggregation (adhesion, activation, aggregation) Studies ACS w/out ST segment elevation Showed composite endpoints of death & MI; deaths & need for revascularizations

Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Agents of GP inhibitors Abciximab (ReoPro) o Monoclonal Ab so caution for allergies o Irreversible inhibition so it has a longer duration of action this can be worrisome bc if the pt starts bleeding, itll take longer for the bleeding to stop so the pt may actually need platelet adhesion to counteract that Tirofiban (Aggrastat) o Reversible inhibition (so quicker offset of action) Eptifibatide (Integrilin) o Reversible inhibition (quicker offset of action) Doses vary by indication (subtle differences btw the IIb IIIa inhibitors) Abciximab (ReoPro) w/ PCI only (start at time of PCI) o 0.25 mg/kg IV bolus over 1 min via separate infusion line 10-60 min before procedure, then 0.125 mcg/kg/min up to 10 mcg/min infusion for 12h. Tirofiban (Aggrastat) medical management only; not with PCI o 0.4 mcg/kg/min x 30 min, then 0.1 mcg/kg/min x 48 96 hrs or at least 12 hrs after angioplasty o Decrease bolus & infusion by 50% w/ CrCl < 30 mL/min Use Tirofiban if want to manage conservatively Typically, most hospitals dont stock tirofiban Seen commonly in rural hospitals without cath labs. They will stock this as their IIb IIIa inhibitor and they will give the pt this initially, and send the pt to a hospital with a cath lab , wherein that hospital will d/c and begin either eptifibatide or abcciximab when starting cath Eptifibatide (Integrilin) w/ or w/out PCI o 180 mcg/kg bolus, then 2 mcg/kg/min x 72 hrs (give 2nd bolus w/ PCI) o decrease infusion by 50% w/ CrCl < 30 mL/min this is nice bc it can be started in the EMS and then can bring pt into cath lab most versatile Contraindications of GP -screen patients for these conditions(any risk of bleeding)
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

o o o

o
o o o

**Active internal bleeding or bleeding disorder in past 30 days (thrombocytopenia) Hx of intracranial hemorrhage, neoplasm, arteriovenous malformation, aneurysm, or stroke w/ in 30 days Major surgical procedure/trauma w/in 1 month Aortic dissection, pericarditis, severe HTN Hypersensitivity Use of another GP IIb/IIIa inhibitor Platelet count < 150,000

USA/NSTEMI other medications Betablockers ACE inhibitors Statin

Treatment within the 1st 24 hours o Beta blockers preferred 1st line for all ACS in absence of contraindications Has anti-arrhythmic, anti-ischemic, antiHTN properties Give PO w/in 24 hrs of MI Dont use IV routinely Continue indefinitely (unless pt has contraindication) o Often times will give oral betablockers in the ER, and then indefinitely Contraindications Signs of HF Low output state Increased risk of cardiogenic shock Relative contraindications PR interval > 0.24 seconds 2nd or 3rd degree AV block asthma or reactive airway disease o Calcium channel blockers BB are preferred, but if bblockers are contraindicated or need add-on therapy, then use CCB Indicated for continuing ischemia when beta-blockers are contraindicated or when pain continues despite adequate does of beta-blockers & nitrates (in absence of EF < 40% or pulmonary edema) w/ EF < 40% or pulmonary edema use amlodipine/felodipine Nondihydropyridines preferred Trends toward increased outcomes w/ verapamil/diltiazem w/ ACS w/out HF Avoid short acting agents - Increased adverse outcomes ACE inhibitors May decrease ventricular remodeling process & decrease ventricular dilation post AMI Early administration (w/in 24 hrs AMI usually after 6 hrs or when stable) decreased mortality Started when patient is stable, but not in the ER Do not use IV increases risk of hypotension Start w/ low oral dose & increase slowly to avoid hypotension (SBP < 100 mm Hg); titrate to maximum tolerated dose In the hospital, titration can be very aggressive and quick Outpatient, titration usually done on a 2 week period based on bp Give to all pts post HF, LVEF < 40%, HTN, DM Contraindications Pregnancy
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

ARBs

Angioedema SBP < 100 of <30mmHg below baseline Clinical relevant renal failure Bilateral renal artery stenosis Hypersensitivity

For those intolerant to ACEI with Heart failure Post AMI w. EF < 40% HTN may use in combo with ACEI with systolic dysfunction HF RX within 1st 24 hrs = BB, CCB, ACEI/ARBS

Lipid Management o Get fasting panel (lipid panel) within 24 hrs of AMI Very important b/c LDL level falls after a heart attack and it stays low for 6 8 weeks after the heart attack Most hospitals have this in protocol o Give statin regardless of baseline LDL cholesterol Start in hospital Give dose to provide at least 30 40% LDL cholesterol reduction o LDL cholesterol goal <70mg/dL

High dose therapy more effective that conventional therapy Trial that was done in patients that were post-MI and they used atorvastatin 80 mg vs pravastatin 40 mg. Pravastatin 40 is a common dose that we would give to get an LDL reduction of 30 40%. So they hit them hard instead of using the standard dosethe pts with the more aggressive therapy had fewer adverse events. (so we now use Lipitor 80mg in MI pathyway)

USA/NSTEMI Medical Management

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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

Anticoagulation = Heparin or LMWH o Can use Fondaparinis if USA/conservative tx remember that ACE-I, we may not start in the ER bc the patient is not stable yet maintenance therapy = ABCDEF

USA/NSTEMI Long Term Medical Treatment Treatment mnemonic CAD o A Aspirin, Antianginal (include SL nitrate), ACEI o B Beta blocker, Blood pressure o C Cigarette smoking, Cholesterol o D Diet, Diabetes o E Education, Exercise o F Fish oil, Flu vaccine USA/NSTEMI Maintenance Doses Maintenance doses Antiplatelet therapy o ASA i. Take 75 162 mg daily indefinitely (doses for PCI trump this) o Clopidogrel i. Use 75 mg w/ ASA > 1 month & ideally up to 12 months without PCI ii. Alternative for ASA allergic patients 1. Give 300 mg PO day one, then 75 mg PO QD indefinitely Post PCI-Antiplatelet Therapy Give ASA 162 325 mg & clopidogrel 75 mg daily o > 1 month after bare metal stenting o > 3 months sirolimus stenting (CYPHER) o > 6 months paclitaxel stenting (TAXUS) After that time o Continue ASA 75 162 mg daily indefinitely for all patients o BMS continue clopidogrel or prasugrel at least 12 months o DES continue clopidogrel or prasugrel at least 12 months o STEMI/NSTEMI w. PCI & no stent long term clopidogrel therapy (1 yr) is reasonable F = Fish oil + Flu vaccine AHA Scientific Statement: Fish Consumption, Fish Oil, Omega-3 Fatty Acids, & Cardiovascular Disease (2002) o Pts w/ documented CHD i. Consume 1 g/day of EPA+DHA, preferably from oily fish ii. Supplements could be considered in consultation w/ physician o Annual flu vaccine Not Recommended for CAD Class III recommendation (there is evidence &/or general agreement that the procedure or treatment
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

is not useful/effective & in some cases may be harmful. o Antioxidants Heart Protection Study & HOPE showed no benefit w/ antioxidant regimen HATS trial showed potential harm o Chelation therapy IV infusion of EDTA May cause hypocalcemia Hormone Replacement Therapy (HRT) HRT w/ estrogen o Discontinue post UA/NSTEMI HRT puts patient at risk for thrombus formation (DVT, pulmonary embolism) o May continue for another compelling indication if weigh risk vs. benefit, greater risk of CV events & breast CA or stroke Do not continue while on bedrest in hospital

NSAID Advice for Pts w. Heart Disease Scientific Statement from AHA -Circulation 2007;115 2/26/07 Black box warning for NSAIDS o CV risk May cause increased risk of serious CV thrombotic events, MI, stroke; may be fatal. Risk may increase w/ duration of use Pts w/ CV ds or risk factors for DV ds may be at greater risk o GI risk Can cause increased risk of serious GI ADE (inflammation, bleeding, ulceration, perforation; may be fatal Occur at any time w/out warning Elderly at greater risk o Dont want to use NSAIDS if dont have to Recommends stepwise approach for treating musculoskeletal pain o Non-pharmacological: PT, exercise, wt loss to reduce stress on joints, heat/cold therapy o APAP, ASA, tramadol, short term narcotic analgesics o Nonacetylated salicylates o Non-COX-2 selective NSAIDs COX-2 selectivity: naproxen < ibuprofen < diclofenac o NSAIDs w/ some COX-2 activity o COX-2 selective NSAIDs o Use lowest possible dose & treat for shortest time possible o w/ hx GI bleed or at high risk of bleeding -use low dose ASA + PPI w/ NSAID FDA Advisory (http://www.fda.gov/cder/drug/infopage/ibuprofen/ science_paper.htm) o Ibuprofen may interfere w/ ASAs ability to irreversibly acetylate the platelet COX-1 enzyme; may reduce protective effects of ASA on risk of atherothrombotic events. Take ibuprofen 400mg at least 30 or 8 hours before low-dose, non-enteric coated ASA Case 1 67 y/o man w/ hx of HTN presents to ER w/ CP (9/10). MONA is given in the ER. Troponin levels and EKG indicate the pt has had a NSTEMI. He is transferred to ICU & cath is scheduled for AM. BB & ACEI are started that. Lipid panel is drawn that day.
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Therapeutics III Dr. Birtcher 1/20/11

ACS (part 1)

What else should be done for this patient? o Antiplatelet (ASA, clopidogrel) o anticoagulant (UFH or LMWH preferred) o IIb IIIa inhibitor (eptifibatide) What meds should the patient receive in the hospital? o Atorvastatin (after procedure) What meds should the pt receive at discharge? o Antiplatelet therapy (ASA, clopidogrel) o BB o ACEI o Statin o Fish oil

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