23 Aug, 2024
Acute Coronary syndrome

 

Acute Coronary Syndrome 

Classification of acute coronary syndrome (ACS) is essential for guiding treatment strategies and assessing prognosis. The primary classification system divides ACS into three main categories based on electrocardiographic (ECG) findings and biomarker levels: 

  1. ST-segment elevation myocardial infarction (STEMI): Characterized by persistent ST-segment elevation on ECG and elevated cardiac biomarkers, typically troponin. STEMI indicates complete coronary artery occlusion and requires immediate reperfusion therapy. 
  2. Non-ST-segment elevation myocardial infarction (NSTEMI): Presents with ST-segment depression, T-wave inversion, or other non-specific ECG changes, along with elevated cardiac biomarkers. NSTEMI usually results from partial or intermittent coronary occlusion. 
  3. Unstable angina (UA): Defined by ischemic symptoms at rest or with minimal exertion, without persistent ST-segment elevation and normal cardiac biomarkers. UA represents a state of myocardial ischemia without detectable myocardial necrosis. 

The distinction between NSTEMI and UA is based on the presence or absence of myocardial necrosis, as indicated by cardiac biomarker elevation. Together, NSTEMI and UA are often referred to as non-ST-segment elevation acute coronary syndrome (NSTE-ACS).  

 

Types 

In the context of acute coronary syndrome (ACS), the term “types” typically refers to the classification of myocardial infarction (MI) based on pathophysiological mechanisms. 

  1. Type 1 MI: Spontaneous MI due to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with resulting intraluminal thrombus. 
  2. Type 2 MI: MI secondary to ischemic imbalance, where a condition other than coronary artery disease contributes to an imbalance between myocardial oxygen supply and demand. 
  3. Type 3 MI: Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes, but death occurring before blood samples could be obtained. 
  4. Type 4 MI: MI associated with percutaneous coronary intervention (4a) or stent thrombosis (4b). 
  5. Type 5 MI: MI associated with coronary artery bypass grafting (CABG). 

 

Mechanism 

Four pathophysiologic processes may contribute.  

  • Plaque rupture or erosion (most common cause): This disruption exposes thrombogenic material to the bloodstream, initiating rapid thrombus formation. The resulting thrombus can partially or completely occlude the coronary artery, reducing blood flow to the myocardium and leading to inadequate oxygen supply to the heart muscle, causing myocardial ischemia. If ischemia persists, it can progress to irreversible myocardial cell death, known as infarction. Additionally, plaque rupture and myocardial injury trigger a local and systemic inflammatory response, exacerbating the initial insult. Microvascular dysfunction, alongside epicardial coronary artery obstruction, can further contribute to myocardial ischemia in ACS. 
  • Dynamic obstruction (e.g., coronary spasm, as in Prinzmetal’s variant angina)  
  • Progressive mechanical obstruction (e.g., rapidly advancing coronary atherosclerosis or restenosis after PCI)  
  • Secondary angina related to increased myocardial oxygen demand (e.g., tachycardia) and/or decreased oxygen supply (e.g., tachycardia, anemia)  

 

Symptoms 

  • Chest pain: Typically, substernal and often radiates to neck, left shoulder and left arm. Occurs with crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than previously)  
  • Angina “equivalents” (occur more often in women, the elderly, patients with diabetes mellitus) are dyspnea and epigastric discomfort. In elderly patients, change in mental status might be the only sign.  

 

Differential Diagnosis  

  • Muscle spasms  
  • Pericarditis  
  • Myocarditis  
  • Expanding aortic aneurysm  
  • Aortic dissection  
  • GERD 
  • Peptic ulcer disease  
  • Pleuritis/pneumonia  
  • Pulmonary embolism  
  • Pneumothorax  
  • Chest-wall syndromes like Herpes zoster  
  • Costochondritis  
  • Cervical disc disease  

 

Diagnostic Approach  

Cardiac markers  

  • Biochemical cardiac markers: Troponins (T or I), CK-MB 
  • With contemporary troponin assays, CK-MB and myoglobin are not useful for diagnosis of ACS. Multiple studies proved this. (Level A evidence by AHA). It may be reasonable to remeasure troponin once on day 3 or day 4 in patients with MI as an index of infarct size and dynamics of necrosis. (IIb recommendation by AHA).  
  • Solitary or minor elevations of troponin cannot be assumed to be due to MI, because troponin elevations can be due to tachyarrhythmia, hypotension or hypertension, cardiac trauma, acute CHF, myocarditis and pericarditis, acute pulmonary thromboembolic disease, and severe noncardiac conditions such as sepsis, burns, respiratory failure, acute neurological diseases, and drug toxicity and chemotherapy. Chronic elevations can result from structural cardiac abnormalities such as LV hypertrophy, CHF or ventricular dilatation and are also common in patients with renal insufficiency. In the diagnosis of NSTEMI, cardiac troponin values must manifest an acute pattern consistent with the clinical events, including ischemic symptoms and electrocardiographic changes. 

 

Diagnostic Procedures  

  • ECG: Changes on ECG in patients with NSTEMI include ST depression, transient ST-elevation, or new T-wave inversion. EKG changes in STEMI include ST-segment elevation in two contiguous leads. Right sided leads (V3 R to V4 R) are typically performed in the case of inferior STEMI to detect evidence of right ventricular infarction. If the initial EKG is negative and suspicion is high, repeat every 15-30 mins.  
  • ECHO to look for regional wall motion abnormalities. 
  • Stress testing: Used to rule out significant coronary artery disease if pain free and markers are negative.  
  • Standard treadmill ECG stress testing if baseline EKG is normal  
  • Perfusion (sestamibi or thallium) or echocardiographic imaging with stress testing, if baseline ECGs are abnormal (e.g., LBBB or LVH) 
  • Pharmacologic stress test for patients who cannot walk  
  • Coronary angiography (for intermediate- and high-risk patients): This remains the gold standard 

 

Risk assessment: In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient’s risk of death and ischemic events and provides a basis for therapeutic decision making. A score of more than 4 has at least 20% mortality risk.  JAMA. 2000;284(7):835-842. 

 

GRACE risk score: It is another alternative to assess the risk of death among patients with acute coronary syndrome. The included variables are Age, heart rate, systolic blood pressure, serum creatinine, Killip class (no CHF vs rales vs pulmonary edema vs cardiogenic shock), elevated cardiac markers, ST segment deviation and cardiac arrest on admission. It includes lot more acute components in comparison to TIMI score. 

 

TIMI Score Calculation (1 point for each): 

  • Age ≥ 65 
  • Aspirin use in the last 7 days (patient experiences chest pain despite ASA use in past 7 days) 
  • At least 2 angina episodes within the last 24hrs 
  • ST changes of at least 0.5mm in contiguous leads 
  • Elevated serum cardiac biomarkers 
  • Known Coronary Artery Disease (CAD) (coronary stenosis ≥ 50%) 
  • At least 3 risk factors for CAD, such as: 
  • Hypertension -> 140/90 or on anti-hypertensives 
  • Current cigarette smoker 
  • Low HDL cholesterol (< 40 mg/dL) 
  • Diabetes mellitus 
  • Family history of premature CAD 
  • Male first-degree relative or father younger than 55 
  • Female first-degree relative or mother younger than 65 

 

Treatment Approach  

  • Bed rest with continuous ECG monitoring 
  • Initial treatment should include aspirin, beta blockers, nitrates, morphine and oxygen.  
  • Hypertension and tachycardia, both of which will markedly increase myocardial oxygen consumption requirements, may be managed with beta blockers and intravenous nitroglycerin.  
  • Patients with unstable angina (UA) or NSTEMI should be treated with an early medical regimen similar to that used in STEMI except for fibrinolytics.  
  • NSAID’s (except aspirin) should be discontinued immediately due to an increased risk of cardiovascular events associated with their use.  
  • Routine use of oxygen in patients without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at six months. AVOID Trial 

 

Invasive strategy vs conservative strategy  

Early invasive strategy for high-risk patients includes treating with anti-ischemic and antithrombotic agents (aspirin and heparin), coronary arteriography within 48 hours of admission, coronary revascularization based on coronary anatomy (PCI or CABG). High risk patients are those who have  

  • Recurrent angina at rest/low-level activity despite treatment  
  • Rising troponins 
  • New ST-segment depression with dynamic EKG changes  
  • Recurrent angina/ischemia with congestive heart failure   
  • LV ejection fraction < 0.40  
  • Hemodynamic instability or angina at rest with hypotension  
  • Sustained ventricular tachycardia 
  • Percutaneous coronary intervention within previous 6 months or prior coronary artery bypass grafting (CABG)  

Conservative strategy or delayed invasive strategy for low-risk patients  

  • Anti-ischemic and antithrombotic therapy, followed by watchful waiting  
  • Coronary arteriography if recurrence of:  
  • Rest pain  
  • ST-segment changes  
  • Evidence of high-risk ischemia on stress test (ischemia at stage 1 or 2, >2 mm ST depressions at any stage, hypotension, ventricular arrhythmias, acute pulmonary edema)  

 

Specific Treatments  

 

Nitrates  

Nitrates must be used with caution or avoided in settings in which hypotension is likely or could result in serious hemodynamic decompensation, such as right ventricular infarction or severe aortic stenosis. In addition, nitrates are contraindicated in patients who have taken a phosphodiesterase inhibitor for erectile dysfunction within the previous 24 hours.  

It acts via increased cyclic GMP, resulting in 

  1. Vasodilation: Primarily affecting the venous system, reducing preload, and to a lesser extent, arterial dilation, reducing afterload. 
  2. Coronary vasodilation: Improving myocardial perfusion, particularly in collateral vessels. 
  3. Platelet inhibition: Reducing thrombotic potential. 
  • Sublingual: Nitroglycerine tablets (0.4mg) given 5 minutes apart, up to 3 doses max.  
  • IV nitroglycerine: If symptoms are not fully relieved with sublingual nitroglycerin, start IV Nitroglycerin, 5–10 μg/min continuous infusion. Increase rate by 10 μg/min every 3–5 minutes (titrated up to 75–100 μg/min) until relief of symptoms or limiting side effects (headache or hypotension with systolic blood pressure < 90 mmHg or > 30% below starting mean arterial pressure). Side effects include headache and hypotension.
  • Topical or oral: Acceptable alternative to intravenous therapy for patients without ongoing or refractory disease. 
    • Transdermal nitroglycerine patch: 0.4–1.2 mg/h for 12–14 hours  
    • Isosorbide dinitrate, sustained release: 10–60 mg PO every 8 hours  
    • Isosorbide-5-mononitrate, oral: 20–30 mg PO bid  
    • Isosorbide-5-mononitrate, oral sustained release: 60–240 mg/d  

 

Beta blockers  

These agents act by competitively antagonizing β-adrenergic receptors, primarily β1 receptors in the heart, resulting in negative chronotropic, inotropic, and dromotropic effects.  

In ACS, beta-blockers are indicated for several reasons: 

  1. Anti-ischemic effects: By reducing heart rate, contractility, and blood pressure, beta-blockers decrease myocardial oxygen demand, potentially limiting infarct size and reducing recurrent ischemia. 
  2. Antiarrhythmic properties: Beta-blockers can suppress ventricular arrhythmias, particularly those mediated by increased sympathetic tone. COMMIT Trial 
  3. Long-term mortality reduction: Multiple clinical trials have demonstrated improved survival with early beta-blocker therapy in ACS, particularly in ST-elevation myocardial infarction (STEMI) 

 

  • Intravenous beta blockade is preferred initially, followed by oral beta blockade targeted to a heart rate of 50–60 beats/min  
  • Choice of specific agent is not as important as long as they get a beta blocker.  
  • If there is concern about patient intolerance due to pulmonary disease (especially asthma), LV dysfunction, risk of hypotension, or severe bradycardia, administer short-acting agents or lower doses rather than complete avoidance of beta-blocker therapy.  
  • Betablockers proven to improve mortality in patients with heart failure from ACS are metoprolol succinate, carvedilol and bisoprolol.  
  • Metoprolol: A cardio selective β1-blocker without intrinsic sympathomimetic activity. 5 mg by slow (over 1–2 min) IV infusion every 5–10 minutes, to total dose of 15 mg. Then follow in 1–2 hours with 25–50 mg PO every 6 hours  
  • Atenolol: Another cardio selective β1-blocker, with a longer half-life than metoprolol. 
  • Carvedilol: A non-selective β-blocker with additional α1-blocking properties, which may provide additional vasodilatory effects. 
  • Propranolol: A non-selective beta-blocker, less commonly used in ACS due to its potential for bronchospasm in susceptible patients.  
  • Esmolol: Starting dosage of 0.1 mg/kg/min IV. Titrate in increments of 0.05 mg/kg/min every 10–15 minutes as tolerated by blood pressure until the desired therapeutic response is obtained. An optional loading dose of 0.5 mg/kg may be given by slow IV administration (2–5 min) for more rapid onset of action.  
  • While the benefits of beta blockers in the pre-reperfusion era were well-documented, their role in the modern era of reperfusion therapy (e.g., percutaneous coronary intervention) and advanced medical therapy (e.g., antiplatelet agents, statins) is less clear.   
  • REDUCE-AMI Trial : Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. 
  • An excellent review article arguing against universal beta blockers. An acute myocardial infarction can be found here. 

 

Morphine sulfate  

  • 2–5 mg IV, and can be repeated every 5–30 minutes as needed  

 

In the context of ACS, morphine is primarily used for: 

  1. Pain relief: Morphine effectively alleviates severe chest pain associated with myocardial ischemia, improving patient comfort and potentially reducing myocardial oxygen demand. 
  2. Anxiolysis: By reducing anxiety and sympathetic activation, morphine may indirectly contribute to a reduction in myocardial oxygen consumption. 
  3. Preload reduction: Morphine induces venodilation, potentially reducing preload and left ventricular end-diastolic pressure, which may be beneficial in patients with pulmonary edema. 

However, the use of morphine in ACS has become controversial in recent years due to several potential drawbacks: 

  • Delayed antiplatelet drug absorption: Studies have shown that morphine can delay and reduce the absorption of oral P2Y12 inhibitors (e.g., clopidogrel, ticagrelor), potentially compromising their antiplatelet effects. 
  • Masking of symptoms: The potent analgesic effect of morphine may obscure ongoing ischemia, potentially leading to delayed recognition of treatment failure or disease progression. 
  • Respiratory depression: Morphine can cause dose-dependent respiratory depression, which may be particularly problematic in patients with compromised respiratory function or those at risk of cardiogenic shock 

 

Current guidelines recommend cautious use of morphine in ACS, reserving it for patients with severe, refractory chest pain despite optimal anti-ischemic therapy. When administered, careful monitoring of respiratory status and hemodynamics is essential. 

 

Calcium-channel blockers  

  • Used in patients whose symptoms are not relieved by adequate doses of nitrates and beta blockers, in those who are unable to tolerate these agents and in variants angina  

 

Statins

High dose statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) to aim for reduction in LDL should be started as soon as possible. PCSK9 inhibitors may be considered in high-risk patients not achieving LDL-C goals with maximum tolerated statin therapy 

 

Clinical Evidence in ACS: 

  1. MIRACL trial: Showed that early, high-dose atorvastatin (80 mg daily) reduced recurrent ischemic events in patients with acute coronary syndromes. 
  2. PROVE IT-TIMI 22 trial: Demonstrated that intensive statin therapy (atorvastatin 80 mg) was superior to moderate-intensity therapy (pravastatin 40 mg) in reducing cardiovascular events after ACS. 
  3. IMPROVE-IT trial: Showed that the addition of ezetimibe to simvastatin provided incremental benefit in reducing cardiovascular events in post-ACS patients 

Inflammation-guided therapy: The CANTOS trial demonstrated that targeting inflammation with canakinumab in addition to statin therapy reduced cardiovascular events, highlighting the importance of residual inflammatory risk 

 

Antithrombotic therapy:  

Oral antiplatelet therapy  

  • The cornerstone of antiplatelet therapy in ACS consists of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor.  
  • A P2Y12 inhibitor (Plavix, Ticagrelor or Prasugrel) in addition to aspirin should be administered for up to 12 months to all patients with NSTEMI, who are treated with either an early invasive or ischemia-guided strategy. (AHA class I recommendation).  
  • Aspirin: 325mg loading dose, followed by 75mg daily indefinitely. The first tablet should be chewed or crushed to establish a high blood level quickly.  ISIS-2 trial demonstrated the efficacy of aspirin in acute myocardial infarction (MI). It showed a 23% reduction in vascular mortality at 5 weeks with aspirin 162.5 mg daily compared to placebo 
  • Clopidogrel: 300mg loading dose, followed by 75mg daily for at least a month in bare metal stents but preferably up to an year and for at least a year in drug alluding stents.  If PCI is planned, 600mg loading dose is given either during or before PCI. Do not give Plavix, if CABG is a possibility.  CURE Trial showed addition of plavix to aspirin in NSTEMI demonstrated a 20% relative risk reduction in the composite endpoint of cardiovascular death, MI, or stroke. CLARITY-TIMI 28 trial showed that adding clopidogrel to aspirin and fibrinolytic therapy in ST-elevation MI (STEMI) improved coronary patency and reduced ischemic complications 
  • Prasugrel ( Effient ): 60mg loading dose followed by 10mg daily – It has a more rapid onset of action and is able to achieve higher degrees of platelet inhibition than clopidogrel. In patients with ACS with scheduled PCI, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. TRITON-TIMI 38. In patients with ACS but not undergoing PCI, prasugrel did not significantly reduce myocardial infarction as compared with clopidogrel. TRILOGY ACS study.  Also, prasugrel given at onset before angiography did not lead to a reduction in the composite primary endpoint when compared with a strategy of administration of prasugrel only at the time of PCI; however, it did lead to an increase in bleeding complications ACCOAST Trial.  AHA do not recommend prasugrel as “upfront” therapy in patients with NSTEMI and recommends only giving at the time of PCI.  AHA/ACC gives a Class IIa recommendations to use prasugrel in preference to clopidogrel for patients with NSTEMI, who undergo PCI and not at high risk of bleeding. Prasugrel should not be administered to patients with prior history of stroke or TIA ( Class IIIB recommendation). The 2020 guidelines from the European Society of Cardiology recommend prasugrel over ticagrelor for NSTE-ACS patients who proceed to PCI, based on the results of the ISAR-REACT 5 trial. Some experts argue that the evidence from the ISAR-REACT 5 trial is not sufficient to definitively favor prasugrel over ticagrelor, 
  • Ticagrelor ( Brilinta), 180mg loading dose followed by 90mg BID — Ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non– procedure-related bleeding PLATO Study.  Ticagrelor differs from the thienopyridines (clopidogrel and prasugrel) in that it binds reversibly rather than irreversibly to P2Y12 platelet receptor and has a more rapid onset of action than clopidogrel. Similar to prasugrel, treatment with ticagrelor leads to more intense platelet inhibition than clopidogrel. AHA/ACC gives Class IIa recommendations to use ticagrelor in preference to clopidogrel for patients with NSTEMI, who undergo PCI/early invasive or ischemia-guided strategy. In patients who had a prior history of stroke, Ticagrelor in comparison to Plavix had higher rates of MI, death and strokes. Circulation. 2012 Jun 12;125(23):2914-21 
  • Ticagrelor vs Prasugrel: ISAR-REACT 5 Trial showed that the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups.  
  • Ticlopidine : Ticlopidine compared to placebo improves outcomes in patients with unstable angina who are not treated with aspirin  

 

Duration of Dual Antiplatelets therapy 

  • DAPT Study (12 vs 30 months) This trial evaluated the benefits and risks of extending DAPT beyond 1 year after drug-eluting stent implantation. It showed that continued DAPT reduced stent thrombosis and major adverse cardiovascular events but increased bleeding 
  • ITALIC Trial (6 vs 12 months): patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT. 
  • PEGASUS-TIMI 54 (Prolonged DAPT): This trial assessed long-term ticagrelor therapy in patients with prior MI, demonstrating a reduction in cardiovascular events but an increase in major bleeding. 
  • TWILIGHT (3 v 12 months): This study showed that ticagrelor monotherapy after 3 months of DAPT reduced bleeding without increasing ischemic events in high-risk patients who underwent PCI. 
  • TICO trial: ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year.  
  • MASTER DAPT One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regards to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events 
  • STOPDAPT-2 (1 vs 12 months): This trial demonstrated that 1 month of DAPT followed by clopidogrel monotherapy was noninferior to 12 months of DAPT in patients undergoing PCI.  
  • STOPDAPT-2 ACS (1 vs 12 months): In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events.   
  • STOPDAPT-3 (1 vs 12 months): The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the dose of prasugrel used in this trial is a low dose, not standar dose.  
  • GLOBAL LEADERS ( 1 vs 24 months): This large-scale trial compared a novel antiplatelet strategy (1 month DAPT followed by 23 months of ticagrelor monotherapy) to standard DAPT in patients undergoing PCI. The novel strategy did not show superiority for the primary endpoint 

My take: After PCI, very short course of DAPT (1 to 3 months) with subsequent P2Y12 inhibitor monotherapy (preferably full dose of Brilinta or Prasugrel) is effective in reducing bleeding events without increasing cardiovascular events compared with prolonged DAPT (12 to 15 months).  SMART-CHOICE ,   N Engl J Med 2019;381:2032-2042 ,  European Heart Journal (2021) 42, 308–319  

 

Intravenous platelet therapy: Glycoprotein IIb/IIIa inhibitors are used when the patient is likely to undergo invasive strategy and has intermediate/high risk features. Especially, when there is a potential for CABG, giving Plavix might delay the surgery and in those circumstances, short acting drugs like integrillin (Half-life is 2.5 hours) should be considered.  

  • Abciximab: Dose: 0.25 mg/kg bolus, followed by infusion of 0.125 μg/kg per min (maximum, 10 μg/min) for 12–24 hours. Duration of action is at least 12 hours and up to a week. Abciximab has been shown to be beneficial for patients with UA/NSTEMI undergoing PCI EPIC Trial , EPILOG Trial and CAPTURE trial.  Abciximab should not be administered to patients in whom PCI is not planned. For UA/NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to omit administration of Abciximab, if bivalirudin is selected as the anticoagulant and at least 300 mg of clopidogrel was administered at least 6 hours earlier than planned catheterization or PCI.  
  • Eptifibatide ( Integrillin ): Two 180 μg/kg boluses 10 min apart, followed by infusion of 2.0 μg/kg per min for 72–96 hours. Duration of action is 4 hours.  
  • Tirofiban: 0.4 μg/kg per min for 30 minutes, followed by infusion of 0.1 μg/kg per min for 48–96 hours  
  • Integrillin and tirofiban show benefit for high-risk patients in whom an invasive management is intended. However, for UA/NSTEMI patients in whom an initial conservative strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.  
  • In the COMPARE trial, eptifibatide demonstrated significant platelet inhibition during PCI in acute coronary syndrome patients, comparable to abciximab and tirofiban 

 

Anticoagulation: usually given at least 48 hrs , preferably for the duration of hospitalization, or until PCI.  

  • Unfractionated heparin  
  • Factor Xa inhibitor like fondaparinux 2.5mg SQ daily. When compared to LMWH , fondaparinux was similar in reducing the risk of ischemic events, but it substantially reduced major bleeding and improves long term mortality and morbidity OASIS-5 Trial. If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis. (AHA Class I recommendation). It is excreted by renal pathways and hence, contraindicated if GFR<30.  Note that fondaparinux 2.5 mg sq daily is the same dose that is utilized for venous thromboembolism prophylaxis.   
  • Direct thrombin inhibitors like bivalirudin or argatroban. It is mainly used in patients with heparin induced thrombocytopenia. Argatroban is metabolized by liver and hence, can be used in renal failure.  
  • Bivalirudin vs Heparin+Integrillin: In patients with ST-segment elevation myocardial infarction who are undergoing primary PCI, anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in significantly reduced 30-day rates of major bleeding and net adverse clinical events. HORIZONS-AMI Trial 
  • Heparin vs bivalirudin: In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization and stent thrombosis was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. MATRIX Trial  
  • Heparin vs bivalirudin: This study compared bivalirudin with heparin in patients undergoing PCI with stable or unstable angina. Bivalirudin was associated with a lower incidence of bleeding without an increase in ischemic events.  ISAR-REACT 3 
  • For patients undergoing a non-invasive (conservative) strategy, UFH should be continued for 2-5 days but atleast for 48 hours, and fondaparinux is continued for the duration of hospitalization or 8 days.   

 

PCI  

  • Includes percutaneous transluminal angioplasty with stenting  
  • For patients who will be referred to the catheterization laboratory within four hours (usually due to patient instability, refractory angina, heart failure, arrhythmia, or hemodynamic instability), UFH or bivalirudin is preferred as opposed to fondaparinux or enoxaparin.  
  • For patients in whom a conservative (non-invasive) strategy is planned, fondaparinux or enoxaparin is preferred to either unfractionated heparin or bivalirudin  
  • Usually recommended for patients with 1- or 2-vessel CAD, patients with multivessel CAD with suitable coronary anatomy, with normal LV function and without diabetes 
  • Complications include dissection or thrombosis of the vessel and uncontrolled ischemia or congestive heart failure  
  • Post Cath complications include groin hematoma, retroperitoneal bleed, compression of femoral nerve from hematoma, femoral artery aneurysm 

 

CABG  

In patients taking a P2Y12 receptor inhibitor in whom CABG is planned and can be delayed, it is recommended that clopidogrel or ticagrelor be discontinued for at least 5 days and prasugrel for at least 7 days before the planned surgery. Aspirin should be continued until the day of surgery. For urgent CABG, Plavix should be discontinued for at least 24 hours.  

 

Indications are Severe CAD (left main, 3-vessel disease with impaired LV function), Diabetes with CAD in ≥ 2 vessels and Coronary vessels or vascular access unsuitable for PCI  

 

Mechanical circulatory support  

  • IABP can be used in cardiogenic shock due to acute coronary syndrome. IABP counter pulsation increases diastolic BP and coronary blood flow and potentially augments cardiac output while diminishing LV end-diastolic pressure. 
  • Impella 
  • LVAD 
  • ECMO for refractory cardiogenic shock 

 

Other ACS pearls  

 

  1. Fondaparinux should not be used as the sole anticoagulant to support PCI. An additional anticoagulant with anti-IIa activity should be administered because of the risk of catheter thrombosis.  
  2. Urgent CABG is indicated in patients with STEMI and coronary anatomy not amenable to PCI who have ongoing or recurrent ischemia, cardiogenic shock, severe HF, or other high-risk features.  
  3. Aspirin should not be withheld before urgent CABG. Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if possible. Short-acting intravenous GP IIb/IIIa receptor antagonists (eptifibatide, tirofiban) should be discontinued at least 2 to 4 hours before urgent CABG. Abciximab should be discontinued at least 12 hours before urgent CABG.  
  4. An angiotensin-converting enzyme inhibitor should be administered within the first 24 hours to all patients with STEMI with anterior location, HF, or ejection fraction less than or equal to 0.40, unless contraindicated  
  5. Emergency revascularization with either PCI or CABG is recommended in suitable patients with cardiogenic shock due to pump failure after STEMI irrespective of the time delay from MI onset.  
  6. The use of intra-aortic balloon pump counter pulsation can be useful for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological therapy. Alternative left ventricular (LV) assist devices for circulatory support may be considered in patients with refractory cardiogenic shock.  
  7. Implantable cardioverter-defibrillator therapy is indicated before discharge in patients who develop sustained ventricular tachycardia/ventricular fibrillation more than 48 hours after STEMI, provided the arrhythmia is not due to transient or reversible ischemia, reinfarction, or metabolic abnormalities  
  8. Aspirin is recommended for treatment of pericarditis after STEMI. Administration of acetaminophen, colchicine, or narcotic analgesics may be reasonable if aspirin, even in higher doses, is not effective. Glucocorticoids and nonsteroidal anti-inflammatory drugs are potentially harmful for treatment of pericarditis after STEMI.  
  9. Dressler syndrome: can happen following MI 7-11 weeks. Treat with high dose aspirin 650 mg four – six times per day.  
  10. The duration of triple-antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor should be minimized to the extent possible to limit the risk of bleeding.   
  11.  ST depression in V1-V2 is suggestive of STEMI in posterior wall.  
  12. First Troponin is negative in 16-25% of AMIs  
  13. Spontaneous coronary artery dissection remains an unusual cause of acute coronary syndrome. It should be included in the differential diagnosis of acute myocardial infarction, especially when it affects young, healthy females  
  14. Diabetes should no longer be considered a risk factor but instead an equivalent to known CAD (Heart 2005;91(3):388)  
  15. Patients with end-stage renal disease (ESRD) have high rates of atherosclerotic heart disease and Cardiac troponin I is a reliable marker of myocardial injury even in patients with ESRD on chronic dialysis. (A study by Henry Ford Hospital in Detroit, measured pre- and post- dialysis cTnI in 113 ESRD patients aged 26-92 with no symptoms of acute coronary syndrome who presented for maintenance dialysis. Nearly all of the patients (94.5%) had hypertension and just over half (53.2%) were diabetic. No patient had a cTnI level positive for AMI either before or after dialysis.)  
  16. Syndrome X: Angina, positive exercise stress but no lesions on cath.  More common in women than men.  
  17. Hyperoxia from high-concentration oxygen therapy causes a marked reduction in coronary blood flow and myocardial oxygen consumption. These physiologic effects may have the potential to cause harm and are relevant to the use of high-concentration oxygen therapy in the treatment of cardiac and other disorders. 

 

Cardiology