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Guidelines on the use of clopidogrel

ACUTE CORONARY SYNDROMES
MANAGEMENT GUIDELINES
(Including ST Elevation MI, Non ST Elevation
MI, Unstable Angina)
July 2006
Trust-wide Guidelines for Calderdale Royal
Hospital and Huddersfield Royal Infirmary
These guidelines are based on ACC/AHA and ESC guidelines, NICE
recommendations, the NSF and previous CCU guidelines from
Huddersfield Royal Infirmary and Calderdale Royal Hospital.
Dr. Bloomer
Dr. Grant
Dr. Rashid
Dr. Stevenson
Dr. Welsh

Acute Coronary Syndromes Management Guidelines
Page 1 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Acute Coronary Syndromes Management Guidelines
Page 2 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

GUIDELINES FOR ACUTE S-T ELEVATION MYOCARDIAL
INFARCTION

Initial assessment and treatment
Initial assessment should include brief history and examination and 12 lead
ECG

Aspirin 300 mg (if not already given by ambulance service) Morphine for pain 5-10mg i.v. initially repeated if necessary after 5 minutes.
Antiemetic should be given with the first dose of morphine unless already
given prior to hospital admission. Metoclopramide 10mg i.v. is first line,
Cyclizine 50mg i.v. second line. Prochlorperazine is not licensed for i.v. use.
Oxygen should be prescribed for the first few hours after acute MI by mask ornasal prongs.
Initial investigations
CKGlucoseRandom cholesterolFull Blood Count CXR later on CCU (not in A and E for straightforward MI).
Thrombolysis (Target time < 30 minutes from admission)
ECG Criteria for Thrombolysis
ST elevation >1mm in 2 or more limb leads or >2mm in 2 or more chest leads Left Bundle Branch Block (unless known to have LBBB previously)Posterior changes: Deep ST depression and tall R waves in leads V1 to V3 Do not thrombolyse ST depression alone, T inversion alone or normal
ECG.

Choice of Thrombolytic Agent:
Streptokinase is first line agent for non-anterior myocardial infarctionTenecteplase is the thrombolytic of choice in the following circumstances: Acute Coronary Syndromes Management Guidelines
Page 3 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Guidelines for thrombolysis (see appendices for administration protocol fortenecteplase and streptokinase) Thrombolysis should be considered for all patients with a qualifying ECGpresenting within 12 hours of onset of chest pain unless there arecontraindications.
The benefit of thrombolysis reduces steadily from the onset of chest pain such
that treatment is contraindicated beyond 24 hours. Decision to treat should
be based on the time of onset of severe or continued pain.
The benefits of thrombolysis are greatest for patients at higher risk i.e.
anterior infarction, LBBB or haemodynamic compromise. Lower risk patients(small infarct, no ongoing pain or haemodynamic compromise) benefit littlefrom late thrombolysis. The risk of haemorrhagic stroke after thrombolysiswith Tenecteplase increases with age and hypertension. This should betaken into account when considering thrombolysis of patients over 75 after 6hours or more.
Severely hypertensive patients can be Thrombolysed after medical control ofblood pressure with either intravenous nitrates 2-10 mg/hour incfreased at 5minute intervals if blood pressure target not reached or intravenousmetoprolol 5-10mg slowly i.v. (unless beta blockers contraindicated). Nitratesand intravenous beta blockers may be combined if necessary.
Stable patients with CHB should be thrombolysed first without temporarypacing as CHB often resolves after thrombolysis.
Acute Coronary Syndromes Management Guidelines
Page 4 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

THROMBOLYTIC THERAPY CHECK LIST
ST elevation (>1mm in 2 or more limb leads or 2mm in 2 or more chest leads) Left Bundle branch block (assume new unless clear evidence from previous
notes) YES/NO
Contraindications to thrombolysis - Absolute Active peptic ulcer or GI bleed in last 3 months Contraindications to thrombolysis – Relative: Consult Registrar/Consultant Traumatic cardiopulmonary resuscitation for this episode Uncontrolled Hypertension: BP>180/110mmHg (repeat half hourly) (see guideline 10)
Please sign to confirm this checklist has been completed and the patient hasbeen informed of the risks of thrombolysis and their verbal consent obtained.
The risk of haemorrhagic stroke is about 1% with thrombolysis (about 0.5%without thrombolysis in acute MI) Signature __________________________________Designation _______________________________Date ___________________ Reason for patient’s refusal of thrombolysis :__________________________________________________________________________________________________________ Acute Coronary Syndromes Management Guidelines
Page 5 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

POST THROMBOLYSIS TREATMENT
Aspirin 75mg daily
Clopidogrel 300mg initially followed by 75mg daily for 28 days After Tenecteplase: Enoxaparin 1mg/kg bd for at least 48 hrsthen 40mg daily until ambulant After Streptokinase: Not routinely required Beta blockers: Oral beta blockers should be given unless there are clear
contraindications such as asthma, severe bradycardia (HR<50) or severe
heart failure. Diabetes and PVD should not be regarded as contraindications
for beta blockade in acute MI. Start after 12 hours.
ACE Inhibitors: Should be given to all patients post MI unless
contraindicated. Mild renal impairment (serum creatinine < 200) should not
be regarded as a contraindication. Renal function must be monitored. Start
after 24 hours.
Statins: Consider for all patients post MI regardless of cholesterol on
admission. First line treatment should be Simvastatin commencing at 40 mg
at night. Simvastatin may increase the risk of myopathy when used with
certain other drugs (incl. Amiodaraone and verapamil - see BNF for full list).
In such cases an alternative should be considered.
Anticoagulation should be considered for patients with atrial fibrillation, left
ventricular aneurysm or LV thrombus.
Potassium Replacement should be considered in patients with K<3.5
especially if arrhythmias are present.
In patient coronary angiography may be required for patients with recurrentchest pain post myocardial infarction or patients with minimal CK rise as aresult of early thrombolysis. In patient angiography is not usually required forpatients who are pain free post MI with a significant CK rise or development ofQ waves on the ECG.
DIABETES MANAGEMENT IN ACUTE MYOCARDIAL INFARCTION
Existing oral hypoglycaemics should be stopped while intravenous insulin isbeing given. All known and newly diagnosed patients with diabetes should betreated with intravenous insulin and glucose for at least 24 hours (see CCUprotocol). Patients already on insulin should be recommenced on theirprevious regime once stable. New diabetics or patients previously on oral Acute Coronary Syndromes Management Guidelines
Page 6 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

hypoglycaemics should be referred to a diabetologist for consideration offurther management.
DISCHARGE FROM CCU
Patients may be discharged from CCU 24-48 hours after admission providedthey are pain free with no arrhythmias. Most patients can be dischargedhome after 4-6 days.
1) All patients with ST elevation MI should be referred to the cardiacrehabilitation team.
Management post discharge. All suitable patients should be exercise testedprior to returning to outpatients. Outpatient follow up should be at 6-8 weeks.
Angiography should be considered for patients with positive exercise test atlow or moderate workload, or post infarction angina.
Acute Coronary Syndromes Management Guidelines
Page 7 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

TREATMENT OF COMPLICATIONS OF MI
Intravenous morphine 5-10 mg particularly if the patient is acutelydistressed Intravenous nitrate infusion should be used providing systolic bloodpressure is >100mm Hg.
Intravenous diuretics (Furosemide 50 mg i.v.) may be requiredparticularly if there is radiological evidence of pulmonary oedema. Hypotension is not a contraindication to diuretics in this case. Patientswith renal impairment usually need higher doses of diuretics for clinicaleffect.
LVF with hypotension/ Cardiogenic shock (BP<90 with oliguria and peripheralshutdown) Treatment as above but avoid nitrates if BP < 100 mmHg.
Consider inotropic support (dobutamine 5-20micrograms/kg/min). Dobutamine may be given peripherally.
N.B: Inotropes have not been demonstrated to improve theoutcome in cardiogenic shock and may increase infarct size dueto increased myocardial oxygen demand. Consider possibility of acquired VSD or severe MR: urgentechocardiography to assess and discuss with LGI cardiology ifappropriate.
Consider emergency referral to LGI cardiology for acuteangioplasty. Where possible these patients should bediscussed with a local cardiologist first.
Right Ventricular infarction: This is a special case presenting as hypotension
in the context of an inferior myocardial infarction without pulmonary oedema.
JVP is usually raised. ST elevation may be seen in leads V3R, V4R.
Treatment is with intravenous fluid infusion (up to 500 ml 5% dextrose or
Haemaccel) with careful monitoring of BP and clinical reassessment for
early signs of pulmonary oedema.
Diuretics should be avoided.
ARRHYTHMIAS
Ventricular ectopics or non sustained VT. Usually no treatment required
unless recurrent long runs of NSVT. Treatment if required is lidocaine
(lignocaine) 50-100 mg i.v. followed by lidocaine infusion.
Sustained Broad Complex tachycardia (usually VT) With haemodynamic compromise (BP<100) proceed to urgentDC cardioversion under general anaesthetic.
Acute Coronary Syndromes Management Guidelines
Page 8 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Without haemodynamic compromise i.v. lidocaine 50-100 mg. Ifsuccessfully terminated follow up with lidocaine infusion for 24-48 hours. If unsuccessful consider i.v. amiodarone 300mg over1 hour or i.v. magnesium sulphate 8mmol over 15 minutesrepeated once if necessary. If medical treatment fails toterminate ventricular tachycardia then DC cardioversion shouldbe performed urgently under general anaesthetic.
Atrial fibrillation or atrial flutter often revert spontaneously. Check potassiumis >4.5 and correct if necessary.
AF with satisfactory rate and blood pressure no treatment isneeded acutely.
AF with high rate but maintained blood pressure. Commence orincrease beta blockade (Metoprolol 25mg t.d.s) if nocontraindication or acute heart failure. If beta blockers cannotbe administered treat with oral or i.v. digoxin. Loading dose is 1-1.5mg in divided doses over 24 hours.
AF with high rate and hypotension consider D.C. cardioversionunder general anaesthetic.
Sustained AF( >12 hours) consider amiodarone orally or i.v.
and anticoagulate if no contraindication. Patients with AF
should be kept on full dose low molecular weight heparin until
warfarinised.
Supraventricular tachycardia (SVT, AVNRT). This is rare post MI.
Treatment is i.v. adenosine 6mg by rapid i.v. bolus injection,
then 12mg if unsuccessful repeated once if necessary.
Adenosine is contraindicated in patients with asthma or
history of wheezing or in patients taking Dipyridamole
(Persantin)

If adenosine contraindicated then i.v. verapamil 5 mg repeatedafter 5 minutes if necessary. Verapamil is contraindicated inpatients with heart failure or taking beta blockers. Other alternatives i.v. amiodarone or D.C cardioversion underGA.
Symptomatic Sinus bradycardia: i.v. Atropine 300-1000 micrograms, repeatedif necessary. High doses of Atropine can cause confusion especially inelderly patients.
2nd degree or 3rd degree heart block with anterior MI temporarypacing ree heart block with inferior MI: i.v. Atropine as above. If sinus rhythm not restored then temporary pacing if Acute Coronary Syndromes Management Guidelines
Page 9 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

haemodynamic compromise (HR< 40, BP <100 systolic) or heartfailure.
Temporary pacing is hazardous and should only be performed by anexperienced operator. The jugular route is safer particularly if thrombolysishas been given. Subclavian or femoral routes are alternatives forappropriately trained practitioners.
Acute Coronary Syndromes Management Guidelines
Page 10 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

GUIDELINES FOR ACUTE CORONARY SYNDROMES PRESENTING WITHOUT
ACUTE S-T ELEVATION

Patients with acute coronary syndromes (excluding ST elevation MI) may presentwith chest pain with either: Definitions:
After assessment with serial ECG, CK and Troponin patients without ST elevationcan be classified as follows: Non ST elevation MI (raised biochemical markers of cardiac damagewith either chest pain or ECG changes) The ACC and ESC recommend a redefinition of MI as above with araised Troponin even in the presence of a normal CK. This has notbeen endorsed by the British Cardiac Society currently. The termAcute Coronary Syndrome could also be used in this case. Unstable Angina (negative Troponin and/or CK with or without ECG
changes). This is a clinical diagnosis including patients with recent
onset severe angina, abrupt worsening of previous angina, or
prolonged anginal pain at rest (>20 mins).
Non cardiac chest pain (negative Troponin and CK, non ischaemicECG, negative ETT, perfusion scan or angiogram) MANAGEMENT
Admission to CCU or cardiology ward. Patients with a clinical
diagnosis of ACS should be admitted to CCU for ECG monitoring if
there are ischaemic ECG changes. If this is not possible then
admission to cardiology ward or MAU for monitoring is acceptable for
patients judged to be at lower risk. Generally patients with no ECG
changes shuold be admistted to MAU with a view to early discharge
(failing which transfer to Cardiology ward). Patients with a high
likelihood of
noncardiac chest pain and a normal ECG should not
routinely be admitted to CCU.
Acute Coronary Syndromes Management Guidelines
Page 11 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Monitoring. Continuous 12 lead monitoring for 24-48 hours especially
if there are ECG changes at presentation or a raised troponin.
Initial investigations:
CXR later on CCU (not in A and E, and only if no recent CXR).
Troponin I level at least 12 hours after onset of suspected cardiacchest pain.
Creatine Kinase on day 2, repeated on day 3 unless Troponin negative TREATMENT
Aspirin 300mg initially followed by 75mg daily Low molecular weight heparin (Enoxaparin 1mg/kg twice daily) Oral or i.v. nitrates for recurrent chest pain Beta blockers unless contraindicated in which case Diltiazem should beconsidered ACE inhibitors should be given to all patients if ischaemic heart diseaseis confirmed unless there are contraindications (serum creatinine>200). Renal function must be monitored.
Clopidogrel: Should be given to the following groups of patients and
continued for 12 months.
Patients with ST depression on resting ECG Patients being transerred to LGI for angioplasty Dose is 300mg initially then 75mg once daily.
Clopidogrel should be not be used routinely for patients withsuspected cardiac pain in the absence of ECG changes orraised Troponin. Acute Coronary Syndromes Management Guidelines
Page 12 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Glycoprotein IIb/IIIa inhibitors. These drugs only to be
prescribed by registrar or consultant grades preferably with
specialist advice. Consider in the following circumstance
Patients with recurrent or persistent chest pain and ECG
changes despite standard treatment (as outlined
above
).
Risk assessment of patients with ACS. High risk is indicated by: History of unstable angina (see definition above) Raised Troponin (except patients with ST elevation MI) General co-morbidity, previous MI, poor LV function ordiabetes.
High risk patients should be considered for in patient coronaryangiography.
Emergency referral for transfer to LGI cardiology should be considered For unstable patients (continuing symptoms, STdepression despite maximal treatment) For patients with arrhythmias of ischaemic origin Referrals to the LGI should be discussed with a Cardiologist duringnormal working hours and with the on call Medical Consultant duringevenings and weekends.
Exercise Tolerance Testing: This is recommended for all patients
able to exercise on a treadmill (except those with LBBB or AF) either
pre discharge or shortly after discharge to select patients for elective
angiography. Beta blockers should continued for exercise testing in
this case.
Cardiac rehabilitation referral: This is appropriate before discharge
for all suitable patients with acute coronary syndromes with positive
Troponin.
Further Outpatient Management: Low risk patients i.e. those patients
considered to have cardiac pain but with negative exercise tests or
exercise tests positive only at high workload (stage 3 Bruce or above)
should be reviewed as out patients in 6-8 weeks for consideration of
coronary angiography if there is recurrent angina.
Acute Coronary Syndromes Management Guidelines
Page 13 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

High risk patients with positive exercise tests at low or moderateworkload (stage 1 or 2 Bruce) should have angiography either as aninpatient or as an urgent outpatient.
Acute Coronary Syndromes Management Guidelines
Page 14 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

PROTOCOL FOR TENECTEPLASE THERAPY
MEDICATION:
Heparin I/V bolus 5000 units if over 67kg or Followed by tenecteplase as a single IV bolus injection over 10seconds (dose based on body weight) Immediately followed by sub-cutaneous injection of Enoxaparin1mg/kg, and continue every 12 hours for 48 hours Start ASPIRIN 300mg orally as soon as possible and then 75mg daily(if no gastrointestinal contra-indications), to be given after food.
Use of post thrombolysis drugs as usual (Beta blockers, Statins, ACEinhibitors) BP, heart rate, ST segment every 15 minutes for 4 hours.
W atch for hypotension, bradycardia, arrhythmias, allergic reaction andanaphylaxis STOP infusion if:
ANTIDOTE - Use Protamine Sulphate as antidote to I/V Heparin.
Tenecteplase dose based on body weight
Patients
Syringe size to use
< 60kg
8000 unit pack of
tenecteplase
10000 unit pack of
tenecteplase
> 90kg
Acute Coronary Syndromes Management Guidelines
Page 15 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

APPENDIX 2
PROTOCOL FOR STREPTOKINASE THERAPY
MEDICATION:
Streptokinase 1,500,000 units in 100mL. of 5% Glucose, infuseslowly I/V over 1 hour.
Therapeutic dose subcutaneous Enoxaparin is not routinely requiredafter Streptokinase.
Start ASPIRIN 300mg orally as soon as possible and then 75mg daily (ifno gastrointestinal contra-indications), to be given after food.
Use of post thrombolysis drugs as usual (Beta blockers, Statins, ACEinhibitors) FOLLOW:-
BP, heart rate, ST segment every 15 minutes for 4 hours.
W atch for hypotension, bradycardia, arrhythmias, allergic reactions andanaphylaxis.
STOP infusion if
ANTIDOTE
Tranexamic Acid 10mg/kg body weight by slow I/V injection(1mL/min); can be repeated after 6-8 hours.
Administer cryoprecipitate if severe bleeding continues.
ANAPHYLAXIS
Restart infusion at half rate when BP recovered Acute Coronary Syndromes Management Guidelines
Page 16 of 16
Prepared by Trust Consultant Cardiologists . July 2006
Approved by Medicines Management Committee . 14th September 2006
Review Date . September 2008

Source: http://homepage.ntlworld.com/gethin.l/Revision/Core/ACS.pdf

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