NOUF ALOUDAH

Acute coronary syndrome

References!

AHA ACS 2007 guidelinespharmacotherapy chapter 16

How it happened?

The cause of an acute coronary syndrome (ACS) is the rupture of an atherosclerotic plaque with subsequent platelet adherence, activation, aggregation, and activation of the clotting cascade. Ultimately, a clot forms and is composed of fibrin and platelets

AHA/ACC

The American Heart Association (AHA) and the American College of Cardiology (ACC) recommend strategies or guidelines for ACS patient care for ST-segment- and non- ST-segment-elevation ACS.

Importance of risk stratification…

Patients with ischemic chest discomfort and suspected ACS are risk-stratified based on a 12-lead electrocardiogram (ECG), past medical history, and results of creatine kinase (CK) MB and troponin biochemical marker tests.

(TIMI scoring)

MI is when troponin is +ve

The diagnosis of myocardial infarction (MI) is confirmed based on the results of the CK MB and troponin tests.

NSEMI

Three key features identifying high-risk patients with non- ST-segment-elevation ACS are

a Thrombolysis in Myocardial Infarction (TIMI) risk score of 5 to 7,

the presence of ST-segment depression on ECG,

and positive CK MB or troponin.

STEMI

Early reperfusion therapy with either primary percutaneous coronary intervention (PCI) or administration of a fibrinolytic agent is the recommended therapy for patients presenting with ST-segment-elevation ACS.

ER and 1st day in the hospital of STE ACS

addition to reperfusion therapy, additional pharmacotherapy that all patients with ST-segment-elevation ACS and without contraindications should receive within the first day of hospitalization and preferably in the emergency department are

intranasal oxygen (if oxygen saturation is low),aspirin, sublingual nitroglycerin, intravenous nitroglycerin,intravenous followed by oral β-blockers, and unfractionated heparin (UFH).

High-risk patients with non-ST-segment-elevation ACS should undergo early coronary angiography and revascularization with either PCI or coronary artery bypass graft (CABG) surgery.

ER and 1st day management of NSTEMI

In the absence of contraindications, all patients with non- ST-segment-elevation ACS should be treated in the emergency department with

intranasal oxygen (if oxygen saturation is low), aspirin, sublingual nitroglycerin, intravenous nitroglycerin, intravenous followed by oral β-blockers, and either unfractionated heparin (UFH) or a low-molecularweight heparin (enoxaparin preferred). Most patients should receive additional therapy with clopidogrel. High-risk patients also should receive a glycoprotein IIb/IIIa receptor blocker.

After MI management

Following MI, all patients, in the absence of contraindications, should receive

indefinite therapy with aspirin, A β-blocker and an angiotensin-converting enzyme (ACE) inhibitorfor secondary prevention of death, stroke, and

recurrentinfarction. Most patients will receive a statin to reduce low-density

lipoprotein cholesterol to less than 70 to 100 mg/dL.Anticoagulation with warfarin should be considered for

patients at high risk of death, reinfarction, or stroke.

Think!

Secondary prevention of death, reinfarction, and stroke is more cost-effective than primary prevention of coronary heart disease (CHD) events.

Go and Read!

EpidemiologyEtiology and PathophysiologyComplicationsClinical presentationDiagnosis

Clinical presentation !

Acute managementMONA:

Oxygen 4 L/min by nasal cannula if O2 sat <90% Aspirin chew and swallow non enteric coated 160-325 mg Nitroglycerin spray or SL 0.4 mg 3 doses to relieve acute chest

pain Morphine Iv 1-5 mg IV every 5-15 min

Non St elevation acute coronary syndromeUnstable angina (UA)

Acute chest pain at rest, > 20 min, St segment depression, T wave inversion, or no ECG changes may occur, but no biomarkers for cardiac necrosis present

Non St elevation myocardial infarction (NSTEMI) Same as above only with posaitive cardiac enzymes

biomarkers of necrosis ) troponin I or T elevation, creatine kinase CK myocardial band(MB) fraction > 5-10% of total CK

Risk stratificationTIMI risk score for stratification non ST

elevation ACS on a 0-7 scale: Predicates likelihood of death, MI, or need for urgent

revascularization in the next 14 days

TIMI Risk factor*CAD risk factors:

Smoking, DM, FHx of CAD

** >50 % stenosis on coronary angiography

Low risk: 0-2

Outpt management

Intermediate risk 3-4

Admit to step down

High risk 5-7

Admit to CCU, consider early PCI invasive strategy

score

criteria

1 Age > 65

1 ≤ 3 risk factors for CAD*

1 Prior Hx of CAD **

1 Aspirin use in past 7 days

1 Anginal events in past 24 hrs

1 St segment depression (<20 min) or transient elevation

1 Cardiac enzyme biomarker elevation (tropinin I or T, CK MB fraction

US/NSTEMI goalsPrevent total occlusion of the infarct related

artery Glycoprotein IIb/IIIa inhibitors +UFH or enoxaparin

(preferred) PCI can be : balloon or stent implementation or both Thrombolytics have shown no benefit in NSTEMI or

UA and ↑bleedingControl chest pain and associated symptoms

Acute treatment of UA/NSTEMIIV NGIf unrelieved pain after three SL NGNo mortality benefitDose : 10 mcg/min titrated to pain relief or

max 200 mcg/minAdverse effect: headache, hypotension,

toleranceCI sildenafil or vardenafil use within 24 hr,

tadalafil use within 48 hr

Beta blockersFirst line for reducing chest pain, infarct size, and left

ventricular wall stressPrimary benefit decreasing myocardial oxygen

demand in UA/NSEMI No mortality benefit proven in NSTEMI(extrapolated

benefit)Shown to reduce frequency of recurrent MI in

US/NSEMI ptMetoprolol 5 mg IV every 5 min 3 times then 50 mg-

100 mg BD or 5 mg IV every 2 min 3 times then 25-50 mg PO every 6 hr for 48hr then 100 mg every 12 hr

ACEIRecommended in pt who are hypertension

after BB and or NG admin., esp. in LV systolic dysfunction or DM with ACS (class I recommendation)

CCBOnly recommended if ongoing ischemia when

BB are CIVerapamil or diltiazem are preferred if

normal LVEF existsNo real benefit on mortality, primarily

symptom relief effects

ClopidogrilCatheterization laboratory evidencePCI-CURE trial (lancet 2001) retrospective analysis of

CURE trail pt. who went for PCI 30 days CV death, MI, urgent revascularization rate was 4.5% in

clopidogril pt versus 6.4 % of placebo pt (p=0.04); clopidogril continue for mean 9 months

CREDO trail (JAMA 2002) randomized double blinded, placebo controlled trail evaluating dose timing strategies 3-24 hr before elective PCI and clopidogril 300 mg loading dose versus no loading dose+aspirin 325 mg Trend toward benefit in pt receiving dose > 6 hr before PCI Risk of excess bleeding if administered in advance, esp. in pt. whom

CABG is planned within 5-7 days after cath.

ClopidogrilRecommended in combination with aspirin for at least

1 month if early non interventional approach planned in non ST elevation ACS and continued for up to 9 months

Recommended in combination with aspirin 325 mg following PCI stent implantation for 1 month following bare metal stent placement, 3 months following sirolimus eluting stent placement, and 6 months following paclitaxel eluting stent placement and ideally up to 12 months following stent placement

Loading dose of 300 mg clopidogril recommended at least 6 hr before PCI

GP IIb/IIIa inhibitorsIrreversible (abciximab) or reversible (tirofiban or epifibatide)

inhibition of glycoprotein IIb/IIIa surface platelet receptor to prevent fibrinogen binding and thus platelet aggregation

Recommended if UA/NSEMI and planning cardiac cath. With possible PCI

Only sig benefit when used in combination with cath. And PCI (TACTIC-TIMI 18 trial, NEJM 2001)

Should be used with aspirin 325 mg and enoxaparin 1 mg/kg SQ BD or UFH 5000 U IV bolus and 1000 U/hr to avoid adverse outcome (higher mortality rate in PRISMA- PLUS trial NEJM 1998 in tirofiban infusion alone without UFH)

Primary benefit in decreasing composite end point of urgent revascularization/MI/death in 30 days

Renal adjucement

Dose for PCI

Dose for UA/NSEMI

FDA approval

GP Iib/IIIa inhibitors

Not necessary, Reticuloendothelial system clearance

0.25 mg/kg IV bolus (10-60 min before PCI) then 0.125 mg/kg/min for 12 hr

Same as PCI dose if cardiac cath. planned soon

PCI only Abciximab(ReoPro)

If Cr.CL. <50 ml/min or Sr.Cr.>2, ↓infusion by 50% to 1 mcg/minCI Sr.Cr. >4

180 mcg/kg bolus 2 × and 2 mcg/kg/min infusion up to 12-24 hr following PCI

180 mcg/kg bolus, then 2 mcg/kg/min infusion up to CABG, PCI or 72 hr

US/NSEMI and elective PCI

Epitfibatide (integrelin)

Cr.Cl. <30 ml/min, reduce loading and maintenance dose by 50%CI. with Sr.Cr. >2.5

Same as UA/NSTEMI dose if continued through cardiac cath (TACTICS-TIMI 18)

0.4mcg/kg/min loading infusion ×30 min, then 0.1 mcg/kg/min for 48 to 96 hr

US/NSEMI only

Tirifiban(aggrastat)

clopidogril aspirin Anticoagulant/ antiplatelets

DL 300 (4×75 tab) then 75 mg/day

162-325 mg then 75-160 mg/day

Dosing

Duration to 9 mo NSEMI or up to 12 mo STEMI for bare stent ≥30 D, DES 3 mo sirilmus, 6 mo paclitaxel

600 DL not recommended routinely yet

Up to 325 mg/day admin. Immed. After ACS diag., after CABG, and 2-24 hr before PCI, continue for 30 D for bare stent implantation, 3 mo for sirolimus stent, 6 mo for paclitaxel stent then 75- 162 mg continued indefinitelyDon’t withhold before CABG

Comments

Withheld up to 5-7 days before CABG

Anaphylaxis, bronchospasm after therapy, serious bleeding

CI

daltaparin enoxaparin UFH Antiplatelets/anticoagulant

120 IU/Kg SQ BID ×5-8 days

1mg/kg SQ BID if Cr.Cl >30 ml/min

IV bolus 60-70 U/kg and 12-15 U/kg/hr infusion

Dosing

Max dose 10,000 IU BID

1mg/kg SQ daily if Cr.CL < 30 ml/min

Max 5000U bolus and 1000U/hr infusion titrate to goal APTT 1.5-2.5 controlLowest dose for NSEMI with lytucs

comments

Sig renal or hepatic dysfunction

Wt >175 kg or Sr.Cr >2.5 not well studied

Previous HIT, serieous active bleeding

CI

clopidogril aspirin Antiplatelts/anticoagulants

CURE trail risk of CV death, stroke, or MI 9.3% versus 11.4% ASA alone (<10 % received GP IIb/IIIa inhibitors and <20% cath.)

ISIS-2 trail risk of death↓23 %

Efficacy

Use if allergy or GI intolerant aspirin, if undergoing non invasive approach (CURE trail) ,add to aspirin ASAP and continue at least 1 month, up to 9-12 mo.

Admin. As soon as possible and continue for life

ACC/AHA recommendation

dalteparin Enoxaparin UFH Antiplatelets/anticoagulants

FRIC trial risk of death, MI, or recent angina 7.6% UFH vs 9.3 % daltaparin p=0.33

ESSENCE trial risk of death., MI, recurrent angina at 14 days 16.6% enoxaparin and 19.8 % UFH

Turpie trial high dose vr low dose SQ UFH at 10 day: 11% thrombosis high dose vs 32%% low dose

Efficacy

Add to antiplatelet therapy (aspirin and/or clopidogril; may give with GP IIb/IIIa inh.

Prefered over UFH in USA/NSTEMI if not in renal failure and no CABG planned within 24 hr, add to antiplatelets therapy; may give with GP IIb/IIIa inh

Add to antiplatelets therapy (aspirin and or clopidogril) should be given with GP IIb/IIIa inh. in high risk pts preferred in STEMI with PCI or thrombolytic

ACC/AHA recommendation