Acute Coronary Syndromes

1
Acute Coronary Syndromes

• Robert Smith
• August 4, 2003

2
Definitions

• Acute coronary syndrome is defined as myocardial
  ischemia due to myocardial infarction (NSTEMI or
  STEMI) or unstable angina
• Unstable angina is defined as angina at rest, new
  onset exertional angina (lt2 months), recent
  acceleration of angina (lt2 months), or post
  revascularization angina

3
(No Transcript)
4
Diagnosis

• Dx of acute coronary syndrome is based on
  history, physical exam, ECG, cardiac enzymes
• Patients can then be divided into several groups
• Non-cardiac chest pain (i.e., Gastrointestinal,
  musculoskeletal, pulmonary embolus)
• Stable angina
• Unstable angina
• Myocardial infarction (STEMI or NSTEMI)
• Other cardiac causes of chest pain (i.e., aortic
  dissection, pericarditis)

5
Pre-test Probability

• In the absence of abnormal findings on physical
  exam, ECG, or enzymes, the pre-test probability
  of acute coronary syndrome must be determined by
  the clinician
• A good history is crucial (is the chest pain
  typical or atypical what are the associated
  symptoms)
• Determination of risk factors is also crucial
  (male, age gt55, smoking, DM, HTN, FamHx,
  hyperlipidemia, known CAD)

6
Pathophysiology of ACS

• Plaque rupture and subsequent formation of
  thrombus this can be either occlusive or
  non-occlusive (STEMI, NSTEMI, USA)
• Vasospasm such as that seen in Prinzmetals
  angina, cocaine use (STEMI, NSTEMI, USA)
• Progression of obstructive coronary
  atherosclerotic disease (USA)
• In-stent thrombosis (early post PCI)
• In-stent restenosis (late post PCI
• Poor surgical technique (post CABG)

7
Pathophysiology of ACS

• Acute coronary syndromes can also be due to
  secondary causes
• Thyrotoxicosis
• Anemia
• Tachycardia
• Hypotension
• Hypoxemia
• Aterial inflammation (infection, arteritis)

8
Treatment of ACS Aspirin

• Aspirin is an antiplatelet agent that initiates
  the irreversible inhibition of cyclooxygenase,
  thereby preventing platelet production of
  thromboxane A2 and decreasing platelet
  aggregation
• Administration of ASA in ACS reduces cardiac
  endpoints

9
Aspirin Trials

• VA Cooperative Study
• Canadian Multicenter Trial
• RISC
• Antithrombotic Trialists Collaberation
• PURSUIT

10
ACC/AHA Guidelines for Aspirin Therapy

• Aspirin should be given in a dose of 75-325
  mg/day to all patients with ACS unless there is a
  contraindication (in which case, clopidogrel
  should be given)

11
Treatment of ACS Nitrates

• Nitroglycerin is considered a cornerstone of
  anti-anginal therapy, despite little objective
  evidence for its benefit
• Benefit is thought to occur via reduction in
  myocardial O2 demand secondary to venodilation
  induced reduction in preload as well as coronary
  vasodilation and afterload reduction
• Titrate to relief of chest pain chest pain
  death of myocardial cells
• No documented mortality benefit

12
Treatment of ACS Beta Blockers

• Beta Blockers reduce myocardial oxygen demand by
  reducing heart rate, contractility, and
  ventricular wall tension
• Administration of beta blockers in ACS reduces
  cardiac endpoints

13
Beta Blocker Trials

• HINT (metoprolol)
• Beta Blocker Heart Attack Trial (propranolol)
• Esmolol vs. placebo
• Carvedilol vs. placebo
• Propranolol vs. placebo
• Overall, treatment with beta blockers reduces
  primary endpoints when compared to placebo

14
AHA/ACC Guidelines for Beta Blocker Therapy

• Intravenous beta blockers should be used
  initially in all patients (without
  contraindication) followed by oral beta blockers
  with the goal being decrease in heart rate to 60
  beats per minute
• A combination of beta blockers and nitrates can
  be viewed as first line therapy in all patients
  with ACS

15
Treatment of ACS Heparin

• Heparin (unfractionated heparin or UFH) has
  traditionally been the mainstay of therapy in
  acute coronary syndromes as its efficacy has been
  documented in several large, randomized trials

16
Heparin Trials

• Heparin/Atenolol Trial
• The Canadian Heparin/Aspirin Trial
• The RISC Trial
• Overall, UFH therapy generally results in an
  important clinical benefit when compared to
  placebo. It is more effective when given in
  continuous infusion rather than intermittent
  boluses

17
Treatment of ACS LMWH

• More recent studies indicate that low molecular
  weight heparin is also effective in the reduction
  of end points such as myocardial infarction or
  death
• Some studies report that LMWH, when used in
  combination with ASA, may be superior to
  continuous infusion of Heparin

18
LMWH Trials

• FRISC
• TIMI IIB
• ESSENCE
• INTERACT
• EVET

19
ACC/AHA Guidelines for Heparin Therapy

• All patients with acute coronary syndromes should
  be treated with a combination of ASA (325 mg/day)
  and heparin (bolus followed by continuous
  infusion with goal of PTT 1-2.5X control) or ASA
  and low molecular weight heparin unless one of
  the drugs is contraindicated

20
Treatment of ACS ACE-I

• The best documented mechanism by which these
  agents act is to reduce ventricular remodeling
  over days to weeks after myocardial damage.
  However, there is data that a mortality benefit
  exists when these agents are used early in the
  course of ACS
• Administration of ACE-I in ACS reduces cardiac
  endpoints

21
ACE-I Trials

• GISSI-3 (Lisinopril)
• ISIS-4 (Captopril)
• SMILE (Zofenipril)
• FAMIS (Fosinopril)
• SAVE (Captopril)
• TRACE (Trandolapril)
• AIRE (Ramiripril)

22
AHA/ACC Guidelines for ACE-I Therapy

• ACE-I should be administered to all patients in
  the first 24 hours of ACS provided hypotension
  and other clear cut contraindications are absent

23
Treatment of ACS Statins

• Statins may be of benefit in ACS
• Possible mechanisms include plaque stabilization,
  reversal of endothelial dysfunction, decreased
  thrombogenicity, and reduction of inflammation

24
Statin Trials

• MIRACL (modest benefit in cardiac endpoints, no
  mortality benefit)
• SYMPHONY (no benefit)
• There is no AHA/ACC class I indication for use of
  statin therapy in ACS

25
Treatment of ACS IIBIIIA Inhibitors

• More potent inhibition of platelet aggregation
  may be of importance in patients with ACS that is
  associated with unstable coronary lesion and
  thrombus formation. This can be achieved by the
  use of GP IIBIIIA inhibitors
• Administration of IIBIIIA inhibitors reduces
  cardiac endpoints

26
IIBIIIA Trials

• PRISM-PLUS (Tirofiban prior to PCI)
• EPIC (Abciximab prior to PCI)
• CAPTURE (Abciximab prior to PCI)
• GUSTO IV-ACS (Abciximab no PCI)
• PARAGON (Lamifiban no PCI)
• PURSUIT (Eptifibatide -- no PCI)
• RESTORE (Tirofiban no PCI)

27
AHA/ACC Guidelines for use of IIBIIIA inhibitors

• A IIBIIIA inhibitor should be administered to all
  patients in whom a percutaneous intervention is
  planned (in addition to heparin/ASA)
• Eptifibatide or Tirofiban should be administered
  to patients with ACS in whom PCI is not planned
  if other high risk features are present (TIMI
  risk score gt3)

28
TIMI Risk Score

• Age gt65 yrs
• Daily ASA Therapy (gt7 days prior to event)
• Symptoms of Unstable Angina
• Documented CAD (stenosis gt 50)
• 3 or more traditional cardiac risk factors
• Elevated cardiac enzymes
• ECG changes

29
TIMI Risk Score

• Score of 3 or less low risk
• Score of 4-5 intermediate risk (use IIBIIIA)
• Score of 6-7 high risk (use IIBIIIA)

30
Treatment of ACS Clopidogrel

• Clopidogrel is a potent antiplatelet agent
• It should be administered to all patients who
  cannot take ASA
• The CURE trial suggests a benefit to adding
  Clopidogrel to ASA/Heparin in patients going for
  PCI
• Give 300 mg loading dose followed by 75 mg/day

31
AHA/ACC Guidelines for Clopidogrel

• Clopidogrel should be administered to patients
  who cannot take ASA because of hypersensitivity
  or gastrointestinal intolerance
• In hospitalized patients in whom an early,
  noninterventional approach is planned,
  clopidogrel should be added to ASA as soon as
  possible on admission and administered for at
  least 1 month and up to 9 months. Do not use
  clopidogrel if there is any possibility patient
  may be candidate for CABG

32
Treatment of ACS Emergent Revascularization

• In the setting of STEMI primary PCI is associated
  with better outcomes than thrombolysis
• Emergent PCI is also indicated in the setting of
  a new LBBB

33
PCI Trials

• PAMI (PTCA vs. thrombolysis)
• Netherlands Trials (PTCA vs. thrombolysis)
• GUSTO IIB (PTCA vs. thrombolysis)
• DANAMI-2 (stenting vs. thrombolysis)
• STAT (stenting vs. thrombolysis)

34
AHA/ACC Guidelines for Primary PCI

• Primary PCI is indicated as an alternative to
  thrombolysis when the following criteria are met
• STEMI or new LBBB
• Can undergo PCI within 12 hours of the onset of
  symptoms
• The MD doing the intervention does more than 75
  PCIs/yr
• The procedure is done in a center that does more
  than 200 PCIs/yr and has surgical backup

35
Conclusions Approach to Chest Discomfort

• Good History and Physical (note time and duration
  of symptoms)
• Careful evaluation of ECG (compare to previous
  when possible)
• Check Cardiac Enzymes
• Monitor on Telemetry
• Oxygen

36
Conclusions Treatment of NSTEMI/USA

• ASA
• NTG (consider MSO4 if pain not relieved)
• Beta Blocker
• Heparin/LMWH
• ACE-I
• /- Statin
• /- Clopidogrel (dont give if CABG is a
  possibility)
• /- IIBIIIA inhibitors (based on TIMI risk score)

37
Conclusions Treatment of STEMI

• ASA
• NTG (consider MSO4 if pain not relieved)
• Beta Blocker
• Heparin/LMWH
• ACE-I
• /-Clopidogrel (based on possibility of CABG)
• IIBIIIA
• /- Statin
• Activate the Cath Lab!!!