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ACUTE CORONARY SYNDROME (ACS)    - Unstable Angina and non-ST segment elevation MI (non-STEMI)          

See   Diff-Diagnosis  |  RX:  "MONA" Medical Approach  | Drug Rx for ACS  | Invasive Approach   
  

Risk Stratification and Management of Patients With Acute Coronary Syndrome
Risk Stratification and Management of Patients With Acute Coronary Syndrome

Extremely High Risk Features

  • Historical features: Recurrent pain despite aspirin, heparin, and medical treatment

  • Lab and ECG features: Elevated troponin with acutely ischemic ECG, including ST elevations with chest pain or persistent new ST depressions >0.5 mm  

  • Treatment: Urgent referral for acute coronary angiography with therapeutic PTCA in a high volume center with door-to-needle time <75 minutes vs. thrombolytics (only if ST-cluster or new LBBB) plus GP IIb/IIIa, heparin, ASA, and medical treatment  

High Risk Features

  • Historical features: Presenting history of recurrent rest pain plus history of CAD/MI

  • Lab and ECG features: Elevated troponin I plus acutely ischemic-appearing ECG   

  • Treatment: Admission to the hospital plus GP IIb/IIIa, heparin, ASA, medical treatment followed by early inpatient investigation (e.g., coronary angiography vs. stress test)  

Moderate Risk Features

  • Historical feature: Recurrent ischemic rest pain plus history of CAD/MI

  • Lab and ECG features: Negative serial troponins with ECG showing nonspecific ST/T wave changes

  • Treatment: Admission to the hospital plus LMWH, ASA followed by possible inpatient investigation (e.g., inpatient stress test)  

Low Risk Features

  • Historical features: Rest ischemic pain, no history of CAD/MI

  • Lab and ECG features: Negative serial troponins and normal (or unchanged) repeat ECG 

  • Treatment: ASA, medical treatment (may include low-molecular-weight heparin), telemetry observation, then outpatient follow-up and investigation  

ACS = acute coronary syndrome; ASA = acetylsalicylic acid; CAD = coronary artery disease; ECG = electrocardiography; LBBB = left bundle branch block; LMWH = low-molecular-weight heparin; MI = myocardial infarction; PTCA = percutaneous transluminal coronary angiography.

Decision for Hospital Admission

  • Risk stratification important: high or moderate risk patients are admitted to hospital

  • Patients with known CAD, age >60-70, ECG changes, hemodynamic changes are high risk

  • Diabetes is a very important risk factor, esp. since patients may not have chest pain.

  • Any elevation in CK-MB or cardiac Troponin (I or T) levels should be admitted

  • Elevated Interleukin 6 (IL6) levels on admission is a marker for outcome and should prompt consideratin of early interventional therapy .

MI Risk Stratification based on History (Chest Pain, CAD, Age), Lab (Troponin or CK-MB levels) and ECG feature:

  • High risk:  elevated cardiac enzymes, ST segment changes, persistent angina at rest

  • Intermediate risk: chest pain and St segment depression stabilized

  • Low risk: no cardiac enzyme elevation, no ST segment changes, and no more chest pain (resolved)

TIMI risk score based on seven risk factors (1 point each)
Consider using the TIMI score to direct therapy in patients with ACS.

  1. Age 65 or older

  2. At least 3 risk factors for CAD

  3. Prior coronary stenosis 50 % or more

  4. ST segment deviation of ECG at presentation

  5. At least 2 anginal events in prior 24 hours

  6. Use of aspirin in previous 7 days

  7. Elevated serum cardiac markers

MI Risk Stratification based on TIMI score -
Cardiac Event Scores (mortality, new or recurrent MI, emergent revascularization) within 14 days:

  • TIMI score 0-1 - event rate 4.7%

  • TIMI score 2    - event rate 8.3%

  • TIMI score 3    - event rate 13.2%

  • TIMI score 4    - event rate 19.9%

  • TIMI score 5    - event rate 26.2%

  • TIMI score 6-7 - event rate 40.9%

    

Definitions   
Definitions of Acute Coronary Syndromes (ACS) describes acute clinically unstable form of coronary ischemia

  1. Unstable angina (USA), crescendo angina, acute coronary insufficiency, preinfarction angina, accelerated angina

  2. Non-Q wave Myocardial Infarction (MI), with non-ST segment elevation MI (non-STEMI)  [non-ST-segment elevation ACS (NSTE-ACS)]
    When the clinical picture of unstable angina is accompanied by elevated markers of myocardial injury, such as troponins or cardiac isoenzymes, non-ST segment elevation MI is diagnosed.

  3. Q-wave (transmural) MI, with non-ST segment elevation   [ST-segment elevation myocardial infarction (STEMI)]

The distinction between non-ST segment elevation MI and ST segment elevation MI is clinically important because early recanalization therapy improves the outcome in ST elevation MI  (STEMI) but not in non-ST segment elevation MI (non-STEMI).

Differential Diagnosis of Severe Chest Pain:  

* Must Rule out:  immediately life-threatening causes of chest pain -

  1. Acute Myocardial Infarction

  2. Unstable angina

  3. Myocarditis

  4. Dissecting aneurysm (ascending aorta)

  5. Pulmonary embolism

  6. Tension pneumothorax

  7. Esophageal rupture

25% of acute aortic syndrome patients present acute coronary syndrome-like ECG patterns.  
Myocarditis may present like myocardial infarction; study of 45 patients admitted for suspected myocardial infarction (prolonged chest pain with ischemic ECG changes and/or elevated serum markers) who had normal coronary angiography and then underwent indium-111-antimyosin antibody scanning and thallium-201 imaging, 35 (78%) had imaging patterns consistent with myocarditis, 6-month follow-up of patients with scans consistent with myocarditis found 81% to have complete functional recovery (J Am Coll Cardiol 2001 Mar 1;37(3):786 in J Watch 2001 May 1;21(9):70)  

   

Features which increase or decrease likelihood of myocardial infarction:

  • most powerful features that increase probability of myocardial infarction are
    new ST-segment elevation, new Q wave, chest pain radiating to both left and right arm simultaneously, presence of third heart sound, and hypotension

  • most powerful features that decrease probability of myocardial infarction are normal ECG result, pleuritic chest pain, chest pain reproduced by palpation, sharp or stabbing chest pain, and positional chest pain

CK-MB elevations can be seen in MI, myocarditis, cardiac contusion, cardiac catheterizations, electroshock cardioversion, cardiac surgery, muscular dystrophy, renal failure, rhabdomyolysis, prostate surgery, cesarean section, athletic activity; CK elevated in conditions with high CK-MB and also cerebrovascular accidents, head injuries, encephalitis, delirium tremens, hepatic coma, uremic coma, epileptic attacks, myositis, alcoholic myopathy, surgery involving skeletal muscle, extreme muscle exertion, hyperkalemia, hypothyroidism, hyperthyroidism, intramuscular injections, pulmonary disorders

Elevated cardiac troponin levels may occur with sepsis, hypotension, hypovolemia, supraventricular tachycardia, atrial fibrillation, left ventricular hypertrophy, coronary vasospasm, congestive heart failure, pulmonary embolism, pulmonary hypertension, emphysema, myocarditis, pericarditis, myocardial contusion, direct current cardioversion, cardiac infiltrative disorders, cardiac transplantation, intracranial hemorrhage or stroke, sympathomimetic drugs, chemotherapy, renal failure, and strenuous exercise (Ann Intern Med 2005 May 3;142(9):786)

troponin T and I useful for diagnosis of acute myocardial infarction but positive and negative likelihood ratios depend on time since onset of chest pain, test especially useful when negative > 8 hours after onset of chest pain

         

"MONA" Rx approach for non-ST-segment elevation acute coronary syndrome

"MONA" approach for non-ST-segment elevation acute coronary syndrome

Patients with acute coronary syndrome, but without ST segment elevation

Institute Rest, "MONA" therapy, & Beta-blockers if no contraindication

Consider Invasive strategy in patients with acute coronary syndrome if clinically indicated (high risk patients):

  1. Cardiac catherization
  2. Percutaneous coronary intervention (PCI)  
  3. Coronary artery bypass graft (CABG)

M for Morphine (1 to 5 mg IV with increments of 2-8 mg IV at 5-15 min intervals as needed to control pain) or other pain med as indicated for resistant pain

O for Oxygen supplement

N for Nitrates/Nitroglycerin for chest pain, sublingual prn or IV or topical nitroglycerin if pain continues.

  • Intravenous NTG may be initiated at a rate of 10 mcg per min and increased by 10 mcg per min every 3 to 5 min until relief of symptoms or blood pressure response is noted. A ceiling dose of 200 mcg per min is commonly used. Systolic blood pressure generally should not be reduced to less than 110 mm Hg in previously normotensive patients or to more than 25% below the starting mean arterial blood pressure if hypertension was present. Nitroglycerin should be avoided in patients with initial systolic blood pressure less than 90 mm Hg  or 30 mm Hg or more below their baseline, or with marked bradycardia or tachycardia. Topical or oral nitrates are acceptable alternatives for patients without ongoing refractory  ischemic symptoms.

  • Avoid nitroglycerin in marked bradycardia, tachycardia, or hypotension and use with extreme caution, if at all, in patients with suspected right ventricular infarction.

A for Antiplatelet therapy, Anticoagulation, ACE inhibitor, Angiotensin receptor blocker           See  Anticoagulation Rx  

  1. Antiplatelet therapy
    • aspirin 165-325 mg initially then 75-160 mg daily indefinitely
      - If aspirin is contraindicated due to hypersensitivity or GI complications, use clopidogrel/Plavix as an alternative antiplatelet agent.
    • clopidogrel (Plavix) 300 mg initially, then 75 mg daily for up 9 - 12 months,
      but should not be used within 5-7 days of CABG (Discontinue for 5 to 7 days before elective coronary bypass surgery)  
      * Administer clopidogrel to patients with ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance.
      * Administer clopidogrel in addition to aspirin as soon as possible to patients with ACS for whom
         - a noninterventional approach is planned, and continue clopidogrel for at least 1 month and for up to 9 months.
         - percutaneous coronary intervention is planned and who are not at high risk for bleeding, and continue clopidogrel for at least 1 month and for up to 12 months.

      * Administer clopidogrel, 75 mg/d, in addition to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not undergo reperfusion

    • glycoprotein IIb/IIIa inhibitor (Abciximab/Reopro, Eptifibatide/Integrilin, Tirofiban/Aggrastat)
      -       Administer eptifibatide/Integrilin or tirofiban/Aggrastat in addition to aspirin and heparin to patients with
      continuing ischemia,
      an elevated troponin level, or
      other high-risk features, TIMI risk score > 4, including angina at rest with ST-segment changes, congestive heart failure, diabetes, or recent MI; and
      plan to do catheterization and percutaneous intervention       ; it may be administered just before percutaneous intervention.
      -       avoid abciximab if PCI not planned
      - Eptifibatide/Integrilin 180 mcg/kg IV bolus load, then 2 mcg/kg/min infusion for up to 72 hr.  If percutaneous coronary intervention (PCI) occurs during the infusion, continue infusion for 18-24 hr after procedure.  
  2. Anticoagulation            See  Anticoagulation Rx  
    • low-molecular-weight heparin (enoxaparin/Lovenox) 1 mg/kg SC q12h for 2 to 8 days, preferred if conservative management, but avoid if creatinine clearance < 60 mL/minute (unless anti-Xa levels monitored) or CABG within 24 hours
    • unfractionated heparin is alternative if early invasive management
      -  Heparin 60 Units/kg (max 4000 units) IV bolus, then 12 units/kg/hr infusion (max 1000 u/hr) IV drip to maintain a PTT at 1.5 - 2.0 x control (~ 50-70 seconds)
    • fondaparinux (Arixtra)  2.5 to 7.5 mg daily as effective as enoxaparin with less major bleeding and lower long-term mortality (level 1 [likely reliable] evidence)
  3. ACE inhibitor:  as Lisinopril, Captopril                  See  BP Medications  
    • for all patients with ejection fraction < 40%, heart failure, hypertension, or other high-risk features
  4. Angiotensive receptor blocker:  as Cozaar       See  BP Medications   
    • if intolerant of ACE inhibitors; avoid combined use with ACE inhibitor acutely but consider combined use if heart failure

"ABCDE" approach for non-ST-segment elevation acute coronary syndrome

A for antiplatelet therapy, anticoagulation, ACE inhibitor, angiotensin receptor blocker (See above)

B for beta blocker, blood pressure control

  1. beta blocker for all patients
  2. blood pressure control
    • ACE inhibitors and beta blockers are first line agents
    • goal blood pressure < 130/85 mm Hg, or < 130/80 mm Hg if diabetes or chronic kidney disease
    • optimal blood pressure may be 125/75 mm Hg

C for cholesterol treatment, cigarette smoking cessation

  1. cholesterol treatment
    • potent, high-dose statin for all patients, goal LDL cholesterol < 70 mg/dL (1.8 mmol/L)
    • ezetimibe or bile acid sequestrant (resin) if needed to achieve goal LDL cholesterol < 70 mg/dL (1.8 mmol/L)
    • consider fibrates or niacin if HDL cholesterol < 40 mg/dL (1 mmol/L) or triglyceride > 150 mg/dL (1.7 mmol/L) despite high-dose statin
  2. cigarette smoking cessation with long-term behavioral support, bupropion and nicotine replacement

D for diet and diabetes management   

E for exercise

  • aerobic and weight-bearing exercise for > 30 minutes 4-5 times/week
  • preferably within cardiac rehabilitation program

Reference - JAMA 2005 Jan 19;293(3):349, correction can be found in JAMA 2005 Apr 13;293(14):1728, commentary can be found in JAMA 2005 May 4;293(17):2092, Am Fam Physician 2005 May 1;71(9):1770 (correction can be found in Am Fam Physician 2006 Jan 15;73(2):212)

       

Drug Treatment for Acute Coronary Syndrome 2009  
Click:  Drug Treatment for Acute Coronary Syndrome 2009  

Drug Therapy for Acute Coronary Syndrome

* Morphine IV- Give effective analgesia promptly as alleviation of pain and anxiety are essential to management.

* Oxygen supplement

* Nitroglycerin  intravenous to a select group of patients with ACS.

* Aspirin therapy promptly and continue indefinitely in all patients with suspected ACS.

* Anti-platelet Rx: clopidogrel/Plavix in selected patients with ACS.

  • it should not be used within 5-7 days of CABG (Discontinue for 5 to 7 days before elective coronary bypass surgery)  
  • Administer clopidogrel/Plavix to patients with ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance.
  • Administer clopidogrel in addition to aspirin as soon as possible to patients with ACS for whom
     - a noninterventional approach is planned, and continue clopidogrel for at least 1 month and for up to 9 months.
     - percutaneous coronary intervention is planned and who are not at high risk for bleeding, and continue clopidogrel for at least 1 month and for up to 12 months.
  • Administer clopidogrel/Plavix, 75 mg/d, in addition to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not undergo reperfusion

* Antithrombin Rx:  Heparin or Low-Molecular-Weight Heparin therapy to both moderate- and high-risk patients with ACS.       See  Anticoagulation Rx  

  • Anticoagulation with subcutaneous LMWH or intravenous UFH  (Unfragmented Heparin) should be added to antiplatelet therapy in patients with likely or definite ACS.
  • LMWH may be advantageous over UFH.
    - Enoxaparin (Lovenox) 1 mg/kg q12h subc
    - Fondaparinux (Arixtra) Weight <50 kg: 5 mg once daily; ; Weight 50-100 kg: 7.5 mg once daiy subc  ; Weight >100 kg: 10 mg once daily 

* glycoprotein IIb/IIIa antagonists in addition to aspirin and heparin in patients with non-ST-elevation MI and as adjunctive therapy in patients with ST-elevation myocardial infarction undergoing primary percutaneous intervention.

* Thrombolytic agent as an alternative to primary percutaneous interventions in suitable candidates with ST-elevation MI.

* ACE inhibitor early in the course of ACS in selected patients

  • within the first 24 hours of acute MI with ST-segment elevation in >=2 anterior precordial leads or with clinical heart failure in the absence of hypotension (systolic BP < 100 mm Hg) or known contraindications to an ACE inhibitor.
  • with acute MI and a left ventricular ejection fraction <40% or patients with clinical heart failure due to left ventricular systolic dysfunction.
  • Consider administering an ACE inhibitor to all other patients within the first 24 hours of acute MI in the absence of hypotension or other contraindications.
  • Consider administering an ACE inhibitor in asymptomatic patients with mildly impaired left ventricular systolic function (ejection fraction 40% to 50%).

* Consider an ARB as an alternative to an ACE inhibitor in patients with heart failure or left ventricular dysfunction after acute MI.

  • Consider initiating therapy with valsartan/Diovan within 10 days after MI as an alternative to an ACE inhibitor in patients with clinical heart failure and/or a left ventricular ejection fraction <=35%.

* Consider early initiation of Cholesterol Med: Statin/ HMG CoA reductase inhibitors in patients with ACS.   See  Cholesterol meds  

  • as atorvastatin/Lipitor, simvastatin/Zocor, lovastatin/Mevacor, fluvastatin/Lescol, or pravastatin/Pravachol  

* Beta-adrenoceptor blockers administer early in the first 24 hours to patients with suspected ACS unless there are significant contraindications of the following:

  • Signs of heart failure
  • Evidence of a low output state
  • Increased risk for cardiogenic shcok
  • Other relative contraindications to Beta-blockade (PR interval >0.24 s, second- or third-degree heart block, active asthma, or reactive airway disease)

* Consider early initiation of carvedilol /Coreg in patients with left ventricular dysfunction after MI.

* Consider early initiation of Aldosterone blocker eplerenone/Inspra in patients with left ventricular dysfunction after MI.

       

Invasive strategy for early revascularization in patients with acute coronary syndrome

Consider primary percutaneous angioplasty as an alternative to thrombolytic therapy in specific subsets of patients with ACS.

  • Consider proceeding directly to primary percutaneous coronary intervention (PCI) for
    patients with ST-segment elevation, new LBBB, or true posterior acute MI     as an alternative to thrombolytic therapy in experienced centers.

Routine invasive strategy in patients with acute coronary syndrome

  1. Percutaneous coronary intervention (PCI)  
  2. Coronary artery bypass graft (CABG)
  • may reduce rate of rehospitalization for acute coronary syndrome (level 2 [mid-level] evidence)
  • may not reduce rate of death or myocardial infarction (level 2 [mid-level] evidence), based on data including short-term and long-term follow-up
  • may reduce rate of death or myocardial infarction after 2 years (level 2 [mid-level] evidence)
  • may reduce rates of death or myocardial infarction for up to 5 years (level 2 [mid-level] evidence)
  • early invasive approach may reduce risk of death or myocardial infarction in elderly patients with acute coronary syndrome, but increased risk of bleeding in patients > 75 year old (level 2 [mid-level] evidence)
  • angiography within 24 hours (compared to after 36 hours) associated with reduced refractory ischemia, and may reduce death and myocardial infarction in high-risk patients (level 2 [mid-level] evidence)

   

Guidelines for Acute Coronary Syndromes:

  • Americam Heart Association and Society of Geriatric Cardiology 2007 guideline for acute coronary care of elderly with non-ST-segment-elevation acute coronary syndromes can be found in Circulation 2007 May 15;115(19):2549 full-text
  • American College of Cardiology/American Heart Association (ACC/AHA) 2007 guideline on unstable angina and non-ST-segment elevation myocardial infarction can be found in J Am Coll Cardiol 2007 Aug 14;50(7):e1 or at National Guideline Clearinghouse 2008 Jan 21:11333, commentary can be found in Lancet 2008 May 10;371(9624):1559 (commentary can be found in Lancet 2008 Aug 16;372(9638):532)
  • Scottish Intercollegiate Guidelines Network (SIGN) national clinical guideline on acute coronary syndromes can be found at SIGN PDF or at National Guideline Clearinghouse 2007 May 28:10585
  • National Heart Foundation of Australia guideline on management of acute coronary syndromes can be found at National Guideline Clearinghouse 2009 Mar 2:13306
  • European Society of Cardiology (ESC) guidelines on diagnosis and treatment of non-ST-segment elevation acute coronary syndromes can be found in Eur Heart J 2007 Jul;28(13):1598 or at National Guideline Clearinghouse 2007 Dec 10:10953
  • American College of Emergency Physicians clinical policy on evalution and management of adult patients with non-ST-segment elevation acute coronary syndromes can be found in Ann Emerg Med 2006 Sep;48(3):270 and at National Guideline Clearinghouse 2007 Jan 22:9736
  • guideline on acute coronary syndromes from 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, hosted by American Heart Association (AHA) can be found in Circulation 2005 Nov;112(22 Suppl):III55 full-text or at National Guideline Clearinghouse 2006 Mar 20:8483, narrative review can be found in Ann Intern Med 2007 Aug 7;147(3):171 (correction can be found in Ann Intern Med 2007 Oct 16;147(8):592), commentary can be found in Ann Intern Med 2008 Mar 18;148(6):485

       
Summary Treatment Recommendations for Acute Coronary Syndrome  
Thrombolytic therapy improves the outcome of patients with ST segment elevation MI but is of no benefit in unstable angina or non-ST segment elevation MI (acute cooronary syndrome) .

Patients with persistent ST segment elevation or new LBBB Myocardial Infarction are considered to have acute MI  

  1. Thrombolysis or percutaneous angioplasty are recommended.

  2. Do not need to wait for return of cardiac enzymes CK-MB or Troponin levels to initiate therapy

9/8/2009 Paper summarizes latest evidence on Antiplatelets and Antithrombotics for ACS   (the Sept. 8, 2009 Journal of the American College of Cardiology)  

A new paper examines the safety, efficacy and timing of antithrombotics in acute coronary syndromes, highlights outstanding controversies and looks at the potential roles of the most promising new drugs in late-stage development.

The analysis, published online and in the Sept. 8 Journal of the American College of Cardiology, summarizes the evidence regarding the use of antiplatelets and anticoagulants for acute coronary syndromes (ACS). Despite great advances in antithrombotic therapies, high risks remain connected with patient comorbidities, drug combinations, dosing adjustments and complex care environments, the authors said. The paper includes the following observations:

Antiplatelets               See  Anticoagulation Rx  

* Data support the use of intravenous glycoprotein IIb/IIIa inhibitors (GPIs) (as Tirofiban/Aggrastat, Eptifibatide/Integrilin, Abciximab/Reopro) in the setting of moderate- or high-risk non-ST-segment elevation ACS (NSTE-ACS), especially in the case of early invasive strategy. Patients presenting with ST-segment elevation myocardial infarction (STEMI) who are undergoing percutaneous coronary intervention (PCI) also may benefit.  For low-risk ACS, GPIs are potentially harmful in troponin-negative patients under conservative management strategy or those with elevated bleeding risk.

* Clopidogrel (Plavix) plus aspirin appears beneficial and safe in patients with STEMI, although there are no safety data with a loading dose for elderly patients receiving fibrinolytics or in patients with STEMI managed without reperfusion therapy.

* The benefits of early pre-loading with clopidogrel  (Plavix) within five days of surgery appear to outweigh the risks of perioperative bleeding.

* Prasugrel has a protective effect in ACS patients and may reduce stent thrombosis, but it may increase major bleeding in patients with a history of stroke or transient ischemic attack, patients age 75 or older and those weighing less than 60 kg.

Anticoagulants             See  Anticoagulation Rx  

* Low-molecular weight heparin (LMWH) has proven superior to short-term unfractionated heparin (UFH) in conservative management of patients with NSTE-ACS, but questions remain about the use of LMWHs in certain settings, including an early invasive strategy, rapid transitions to catheterization lab, procedural anticoagulation and in conjunction with fibrinolytic therapy for patients with STEMI.

* Adding UFH to enoxaparin in an uncontrolled fashion may result in increased bleeding complications.

* Continued in-hospital administration of enoxaparin  (Lovenox) may provide substantial additional benefit in patients with STEMI.

* Overall, LMWH appears to be a viable option across a wide spectrum of patients presenting with ACS, suggesting that it should be investigated further for potential use in other settings such as primary PCI for acute MI.

* The factor Xa inhibitor fondaparinux (Arixtra) appears to reduce the risk of bleeding and lowers long-term morbidity and mortality compared with enoxaparin in NSTE-ACS, although there were more catheter-related thrombi. However, fondaparinux appears to be associated with a risk of harm (increased rate of coronary complications) in STEMI patients treated with primary PCI.

* Promising drugs in the pipeline include novel anticoagulants that inhibit propagation of coagulation by targeting factor IXa, Xa or their cofactors. These agents are based upon aptamer technology, which addresses control and reversibility in acute care settings, which has potential to play a crucial role during and after cardiopulmonary bypass for coronary surgery and other situations where bleeding occurs. However, the authors noted that long-term investments are needed to gain clinical and regulatory acceptance of these new drugs.

       
Diagnostic Evaluation of Rule Out MI Patients:

  1. History & physical,
      - Symptoms as  recent or increasing chest pressure, tightness, or heaviness; pain that radiates to the jaw, shoulders, back, one or both arms, expecially with less activity or at rest, associated with nausea & vomiting, diaphoresis and shortness of breath.
      - Signs as abnormalities in heart rate or blood pressure, tachypnea, pallor, new murmurs or gallops, signs of CHF, fever.
    Serial ECG and

  2. Lab tests: cardiac enzyme CK: troponin T or I, or CK, CK-MB levels  

  3. Stress echocardiography appears more cost-effective than exercise ECG as initial test for patients with suspected acute coronary syndrome and negative cardiac troponin test

  4. If no acute MI, next screening tests include Exercise treadmill test +/- Sestamibi scan or Adenosine Sestamibi scan, Dobutamine echocardiography, or Coronary angiography

Troponin testing may allow rapid and safe discharge from emergency department for patients with acute chest pain and low risk of cardiac events

  • study of 773 consecutive patients with acute chest pain < 12 hours without ST segment elevation, 47 had myocardial infarction, 315 had unstable angina

  • troponin T and troponin I tested in each patient, repeated after at least 4 hours and repeated again if necessary to test at least 6 hours after onset of pain

  • for diagnosis of myocardial infarction (based on CK > 2 times normal and elevated CK-MB)

    • troponin T had 93.6% sensitivity, 88.5% specificity, 36% positive predictive value and 99.5% negative predictive value

    • troponin I had 100% sensitivity, 81.9% specificity, 27.5% positive predictive value and 100% negative predictive value

  • troponin I
    < 0.6 ng/mL     negative for myocardial ischemia/infarction,
    0.6-1.4 ng/mL suggests myocardial ischemia with strong probability for serious cardiac event within 3-6 months,
    > 1.5 ng/mL strongly suggests AMI

  • for diagnosis of myocardial infarction or unstable angina

    • troponin T had 31.5% sensitivity, 97.6% specificity, 92.7% positive predictive value and 59.3% negative predictive value

    • troponin I had 44.5% sensitivity, 97.3% specificity, 94.2% positive predictive value and 64% negative predictive value

  • for prediction of cardiac event (death or myocardial infarction) before 30 days after discharge

    • troponin T had 79% sensitivity, 86% specificity, 22% positive predictive value and 98.9% negative predictive value

    • troponin I had 94.1% sensitivity, 80% specificity, 19% positive predictive value and 99.6% negative predictive value

  • troponin T had false positives with renal failure (7 patients had positive troponin T but negative troponin I, 6 of whom had renal failure)

Note:

  • ACS patients with Troponin T < 0.01 ug/L are at very low risk of subsequent mortality; predicts < 1% risk of MI within 30 days

  • troponin I equally sensitive and more specific than CK-MB for myocardial infarction

  • troponin T less sensitive and less specific than CK-MB for myocardial infarction

  • both troponin I and troponin T have prognostic value for future cardiac events

  • troponin I is preferred cardiac enzyme for evaluating suspected myocardial infarction

  • MPO (Myeloperoxidase) plasma levels, even a single MPO level, at presentation of chest pain predicted risk of major cardiac events at 1 and 6 months; risk rations in the 2-4x range.  SerumMP are probably the most sensitive marker for ruling out MI.

  • BNP (B-Type Natriuretic Peptide) elevation in ACS is correlated with poor outcomes as death, recurrent MI, and heart failure.

 

Strategies according to risk stratification
High-risk ACS patients

Patients judged to be a high risk for progression to myocardial infarction or death include those:

  • with recurrent ischaemia (either recurrent chest pain or dynamic ST-segment changes, in particular ST-segment depression, or transient ST-segment elevation)
  • with early post-infarction unstable angina
  • with elevated troponin levels
  • who develop haemodynamic instability within the observation period
  • with major arrhythmias (repetitive ventricular tachycardia, ventricular fibrillation)
  • with diabetes mellitus
  • with an ECG pattern which precludes assessment of ST-segment changes

In these patients the following strategy is recommended:

  • While waiting and preparing for angiography, treatment with
    low-molecular-weight heparin     should be continued. Administration of
    glycoprotein IIb/IIIa receptor inhibitor will be started and continued for 12 (abciximab) or 24 (tirofiban, eptifibatide) hours after the procedure if angioplasty is performed.
  • Coronary angiography should be planned as soon as possible, but without undue urgency.
    A relatively small group of patients will require a coronary angiogram within the first hour.
    -  This includes patients with severe ongoing ischaemia, major arrhythmias, haemodynamic instability.
    In most cases coronary angiography is performed within the 48 hours, or at least within hospitalization period.
    -  In patients with lesions suitable for myocardial revascularization, the decision regarding the most suitable procedure will be made after careful evaluation of the extent and characteristics of the lesions, where appropriate, in consultation with surgical colleagues. In general, recommendations for the choice of a revascularization procedure in unstable angina are similar to those for elective revascularization procedures. In patients with single vessel disease, percutaneous intervention of the culprit lesion is the first choice. In patients with left main- or triple-vessel disease, coronary artery bypass grafting (CABG) is the recommended procedure, particularly in patients with left ventricular dysfunction, except in cases of serious co-morbidity, which contraindicates surgery. In double-vessel and in some cases of triple-vessel coronary disease, either percutaneous intervention or coronary bypass surgery may be appropriate. In some patients, a staged procedure may be considered, with immediate balloon angioplasty and stenting of the culprit lesion and subsequent reassessment of the need for treatment of other lesions, either by a percutaneous procedure or coronary artery bypass grafting (CABG). If percutaneous intervention is the selected procedure, it may be performed immediately after angiography in the same session.
  • Patients with suitable lesions for percutaneous coronary intervention (PCI) will receive clopidogrel. In patients planned for CABG clopidogrel will be stopped, except if the operation is deferred. In that case, clopidogrel should be stopped about 5 days before operation.
  • If angiography reveals no options for revascularization, owing to the extent of the lesions and/or poor distal run-off, or reveals no major coronary stenosis, patients will be referred for medical therapy. The diagnosis of an acute coronary syndrome may need to be reconsidered and particular attention should be given to possible other reasons for the presenting symptoms. However, the absence of significant stenosis does not preclude the diagnosis of an acute coronary syndrome. In selected patients, an ergonovin test may detect or rule out excessive coronary vasoconstriction.

Low-risk ACS patients

Patients considered to be at low risk for rapid progression to myocardial infarction or death include those:

  • who have no recurrence of chest pain within the observational period
  • without ST-segment depression or elevation but rather negative T waves, flat T waves or normal ECG
  • without elevation of troponin or other biochemical markers of myocardial necrosis on the initial and repeat measurement (performed between 6 to 12 hours)

In these patients the strategy is as follows:

  • Oral treatment should be recommended, including aspirin, clopidogrel (loading dose of 300 mg followed by 75 mg daily), beta-blockers and possibly nitrates or calcium antagonists.
  • Secondary preventive measures should be instituted as discussed below (under Long-Term Management).
    Low-molecular-weight heparin     may be discontinued when, after the observation period, no ECG changes are apparent and a second troponin measurement is negative.
  • A stress test is recommended.
    The purpose of such a test is first, to confirm or establish a diagnosis of coronary artery disease and when this is yet uncertain, second, to assess the risk for future events in patients with coronary artery disease.
  • In patients with significant ischaemia during the stress test,
    coronary angiography and subsequent revascularization, should be considered, particularly when this occurs at a low workload on the bicycle or treadmill.
    It should be appreciated that a standard exercise test may be inconclusive (no abnormalities at a relatively low workload). In such patients an additional stress echocardiogram, or stress myocardial perfusion scintigram may be appropriate.
  • In some patients, the diagnosis may remain uncertain, particularly in patients with a normal electrocardiogram throughout the observation period, without elevated markers of myocardial necrosis, and with a normal stress test and good exercise tolerance.
    The symptoms resulting in presentation to the hospital were probably not caused by myocardial ischaemia, and additional investigations of other organ systems may be appropriate. In any case, the risk for cardiac events in such patients is very low. Therefore, additional tests can usually be performed at a later time, at the outpatient clinic.

Long-Term Management

  1. Aggressive and extensive risk factor modification is warranted in all patients following diagnosis of acute coronary syndrome.
  2. It is mandatory that patients quit smoking: patients should be clearly informed that smoking is a major risk factor. Referral to smoking cessation clinics is recommended, and the use of nicotine replacement therapy should be considered.
  3. Blood pressure control should be optimized.
  4. Aspirin should be prescribed (75-150 mg).
  5. Clopidogrel 75 mg should be prescribed for at least 9, possibly 12 months, and the dose of aspirin should be reduced to 75-100 mg.
  6. Beta-blockers improve prognosis in patients after myocardial infarction and should be continued after acute coronary syndromes.
  7. Lipid lowering therapy should be initiated without delay.
  8. A role for angiotensin-converting enzyme (ACE) inhibitors in secondary prevention of coronary syndromes has been suggested.
  9. Since coronary artherosclerosis and its complications are multifactorial, much attention should be paid to treat all modifiable risk factors in an effort to reduce recurrence of cardiac events.

       

REF:  

         2009