STEMI (ST Elevation Acute Myocardial Infarction / Acute Coronary Syndrome)
The focus of this chapter is the diagnosis and management of patients with ST-elevation myocardial infarction (STEMI). ECG changes in acute STEMI have already been discussed in the chapter ST Elevations in Ischemia and Infarction. However, ECG criteria and characteristics of STEMI will be repeated below. Management of STEMI will be discussed in detail with emphasis on evidence-based therapies. The clinical definitions and recommendations presented in this chapter are in line with guidelines issued by the American Heart Association (AHA), American College of Cardiology (ACC) and the European Society for Cardiology (ESC). A large body of science supports the concepts and recommendations presented in this chapter.
Chest pain (or chest discomfort) is the hallmark of myocardial ischemia and it is particularly pronounced in patients with acute STEMI. The reason symptoms are more severe in patients with STEMI, as compared with NSTEMI and unstable angina (UA), is because the extent of the ischemia is greater in STEMI (i.e a larger portion of the myocardium is affected). For the same reason, patients with STEMI are at higher risk of malignant ventricular arrhythmias in the acute phase. Ventricular tachycardia (VT) and ventricular fibrillation (VF) causes the vast majority of all deaths in the acute phase of STEMI. Death due to pumping failure (cardiogenic shock) is much less common in the acute phase.
Optimal STEMI care requires a sophisticated apparatus including the EMS (Emergency Medical Service) and the hospitals. Most communities have therefore created a regional system of STEMI care which aim to rapidly identify and handle patients with STEMI. The dispatch center, ambulance, emergency department (ED), catheterization laboratory and cardiology ward must act in concert to provide optimal care. The entire chain of care, from prehospital assessment to hospital discharge will be covered in this chapter.
The diagnosis is often straightforward using the electrocardiogram (ECG). Prehospital personnel have proven to be highly capable of recognizing STEMI using the 12-lead ECG. Moreover, patients who utilize the EMS may have better outcomes, since several evidence-based therapies (including reperfusion) can be given in the prehospital setting.
STEMI is treated with anti-ischemic agents, antithrombotic agents, anticoagulants and reperfusion (PCI or fibrinolysis). Virtually all patients with acute STEMI should be referred to the catheterization laboratory for angiography with the intend to perform PCI (percutaneous coronary intervention). Anti-thrombotic medications, anticoagulants and reperfusion reduces mortality by counteracting thrombus formation and restoring coronary blood flow.
Diagnosis and definition of STEMI (ST Elevation Mycoardial Infarction)
ST Elevation Myocardial Infarction (STEMI) is an acute coronary syndrome (ACS). There are two types of acute coronary syndromes:
- STE-ACS (ST Elevation Acute Coronary Syndrome) is defined by the presence of significant ST segment elevations on ECG. If a patient with such ECG changes develops myocardial infarction (defined by elevated troponin levels in blood), the condition is classified as STEMI (ST Elevation Myocardial Infarction). STEMI is only diagnosed when elevated troponin levels have been confirmed; until then, the condition is classified as STE-ACS. However, in clinical practice, STE-ACS and STEMI are equivalent because virtually all patients with chest pain and ST elevations on ECG will have elevated troponin levels.
- NSTE-ACS (Non ST Elevation Acute Coronary Syndrome) is defined by the absence of ST segment elevations on ECG. All patients who do not meet criteria for STEMI will automatically be classified as NSTE-ACS. The majority of these patients will exhibit elevated troponin levels, which classifies the condition as NSTEMI (Non ST Elevation Myocardial Infarction). Those who do not display elevated troponin levels are classified as unstable angina pectoris (UA). Patients with NSTE-ACS typically present with ST segment depressions and/or T-wave inversions.
In summary, a diagnosis of acute myocardial infarction (MI) requires evidence of myocardial necrosis, which implies that troponin levels must be increased. The difference between STE-ACS (STEMI) and NSTE-ACS (NSTEMI, UA) is merely the presence of ST segment elevations on the ECG. The subdivision into STEMI (STE-ACS) and NSTE-ACS may seem somewhat arbitrary, but it actually separates two different conditions (with respect to the coronary artery thrombosis) which requires different management to optimize survival. The flow-chart below illustrates the natural history of acute coronary syndromes and the classification into STEMI (STE-ACS) and NSTE-ACS (NSTEMI, UA).
STE-ACS (ST Elevation Acute Coronary Syndrome) and STEMI (ST Elevation Myocardial Infarction)
STEMI is a clinical syndrome defined by symptoms of myocardial ischemia – notably chest pain/discomfort – in association with ST segment elevations on the ECG and elevated troponin levels. As mentioned above, virtually all patients with clinical signs of myocardial ischemia (e.g chest pain) and ST elevations on ECG will have elevated troponin levels, which is why STE-ACS is clinically equivalent to STEMI. As noted in Figure 1, STEMI is the result of a thrombosis located proximally in the coronary artery. The thrombosis should be so large that it causes a complete occlusion (obstruction of blood flow) in the artery. Such occlusions will lead to severe ischemia in the myocardium supplied by the artery and its branches. The ensuing ischemia is transmural, which means that it affects the entire muscle layer, from the endocardium to the epicardium (Figure 2).
Video 1 and Video 2 shows the obstruction of blood flow in a patient with STEMI (Video 1) and the result of PCI (Video 2).
Video 1 (above): This angiogram shows a catheter placed in the left circumflex coronary artery. The artery is occluded and therefore not filled with contrast.
Video 2 (above): The same patient after balloon inflation and placement of a stent. Flow can now be visualized in the artery. Source: Todt T et al: “Relationship between treatment delay and final infarct size in STEMI patients treated with abciximab and primary PCI”. BMC Cardiovascular Disorders.
Related article: Evaluation and management of patients with chest pain.
Epidemiology of STEMI (ST Elevation Myocardial Infarction)
Incidence of STEMI
In 1990 STEMI accounted for nearly 50% of all cases of acute coronary syndromes (ACS). Since then the incidence of STEMI has declined steadily and in recent years STEMI represents 25% to 40% of all cases of ACS. Meanwhile, the incidence of NSTEMI has increased which is presumably due to the increasing sensitivity of troponin assays. Many patients who were previously classified as unstable angina are nowadays diagnosed as NSTEMI because the troponin assays are capable of detecting extremely small elevations in troponin.
Mortality in STEMI
Mortality in STEMI has also declined dramatically in the past decades. In-hospital mortality is now 5% and 1-year mortality is 7–18%. Roughly 70% of patients with STEMI are men. Women, on the other hand, have longer delay from symptom onset to first medical contact and women are also less likely to receive evidence based interventions, such as PCI and fibrinolysis. Women also tend to present with atypical symptoms more frequently than men.
Almost one in four patients with STEMI have diabetes, which confers an increased risk of complications (e.g heart failure) and death (both in the acute setting and in the long-term). Elderly and patients with renal disease are also less likely to receive recommended interventions, despite evidence of benefit from such interventions.
ECG (EKG) in STEMI (ST Elevation Myocardial Infarction)
The ECG is the key to diagnose STEMI. ECG criteria for STEMI are not used in the presence of left bundle branch block (LBBB) or left ventricular hypertrophy (LVH) because these conditions cause secondary ST-T changes which may mask or simulate ischemic ST-T changes. ST segment elevation is measured in the J-point and the elevation must be significant in at least 2 contiguous ECG leads. Contiguous leads refers to leads that direct neighbours and reflect the same anatomical area; such as anterior leads (V1–V6), inferior leads (II, aVF, III) and lateral leads (I, aVL). For example, leads V3 and V4 are contiguous; V1 and V2 are also contiguous; aVL and I are also contiguous; V3 and V5 are not contiguous, because lead V4 is placed between these leads.
J point elevation of ≥1 mm is considered significant in all leads except from leads V2 and V3. This is explained by the fact that most women and men display a slight ST elevation (J point elevation) in V2 and V3, which is why a higher J point elevation is required in these leads. Refer to Box 1 for all ECG criteria for STEMI.
BOX 1: Criteria for STEMI
New ST segment elevations in at least two anatomically contiguous leads:
- Men age ≥40 years: ≥2 mm in V2-V3 and ≥1 mm in all other leads.
- Men age <40 years: ≥2,5 mm in V2-V3 and ≥1 mm in all other leads.
- Women (any age): ≥1,5 mm in V2-V3 and ≥1 mm in all other leads.
- Men & women V4R and V3R: ≥0,5 mm, except from men <30 years in whom the criteria is ≥1 mm.
- Men & women V7-V9: ≥0,5 mm.
In patients with STEMI the ECG leads displaying ST segment elevations actually reflects the ischemic area. This means that ST elevations in leads V3 and V4 (anterior chest leads) reflect anterior ischemia, and ST elevations in leads aVF and II reflect inferior ischemia. Figure 3 illustrates the four walls of the left ventricle and the ECG leads that reflect these walls.
Characteristics of ischemic ST elevations
ST segment elevations with straight (horizontal, upsloping or downsloping) or convex ST segment strongly suggest acute STEMI (Figure 4A). Concave ST segment elevations, on the other hand, are much less likely to be caused by ischemia (Figure 4B). This is noted in both North American and European guidelines. However, a concave ST segment does not rule out STEMI, it only reduces the probability of STEMI. Refer to Figure 4.
Other causes of ST segment elevations
With respect to differential diagnostics, at least 16 other conditions may also cause ST elevations. These conditions have been discussed in detail in the article ST elevations in ischemia/infarction and differential diagnoses. Some of these conditions are benign whereas others are potentially life-threatening. These conditions are as follows:
- Male/female pattern (“Normal ST segment elevation”)
- Early repolarization syndrome
- Left ventricular hypertrophy (LVH)
- Left bundle branch block (LBBB)
- Acute pericarditis (myocarditis, perimyocarditis)
- Brugada syndrome
- Pulmonary embolism
- Aortic dissection
- Arrhythmogenic right ventricular cardiomyopathy (dysplasia) – ARVD/ARVC
- Pre-excitation (Wolff-Parkinson-White syndrome)
- Electrical cardioversion
- Takotsubo cardiomyopathy (broken heart syndrome, apical ballooning syndrome)
- Prinzmetal’s angina (variant angina, coronary artery vasospasm)
- Hypothermia & hypercalcemia
- Left ventricular aneurysm
Reciprocal ST depressions, T-wave inversions (negative T-waves) and pathological Q-waves in STEMI
In most cases the ST elevations are accompanied by reciprocal ST segment depressions. Such ST depressions are mirror images of the ST elevations and therefore occurs in leads which are in the opposite angle, compared with the leads displaying ST elevations. Figure 5 presents two patients with acute STEMI and there are evident reciprocal ST depressions in both cases.
In patients with STEMI, the ST segment elevations are gradually normalized (within 15 hours) and followed by T-wave inversions, which may persist for a month or even longer. Pathological Q-waves may appear if the infarct area is large (the majority of patients develop such Q-waves). These Q-waves are abnormally wide and deep (Figure 5). They testify that the infarction was extensive. Infarctions that result in pathological Q-waves are referred to as Q-wave infarctions.
Aborted myocardial infarction (MI)
On rare occasions the thrombus may resolve (either spontaneously or by means of reperfusion therapy) before the infarction process begins. In this case the troponin levels are not elevated and the condition is classified as unstable angina pectoris or aborted myocardial infarction. This is, however, rare because virtually all cases of STE-ACS progress to STEMI.
The ECG may be treacherous in some patients with acute transmural ischemia (i.e STEMI). For example, some patients have underlying ECG abnormalities (e.g LBBB) that make it very difficult to detect ischemic ECG changes. Other patients may have acute transmural ischemia located in areas not detected by any of the 12 standard leads. Thus, there are circumstances that all clinicians must be aware of.
Left bundle branch block (LBBB) in patients with acute myocardial infarction (MI)
Left bundle branch block (LBBB) causes pronounced ST-T changes (which are expected in all patients with LBBB). These changes include both ST elevations (V1–V3) and ST depressions (V4, V5, V6, aVL, I). The T-waves are typically inverted in leads with ST depressions (Figure 6). Hence, LBBB causes ST-T changes which are also seen in patients with acute STEMI. Moreover, in patients with LBBB who develop STEMI, the ECG recorded during STEMI may not differ from their baseline ECG with LBBB; i.e ischemic ST-T changes may not come to expression in the presence of LBBB. Hence, LBBB may both imitate and mask acute STEMI. This is further complicated by the fact that many patients with chest pain and a new LBBB (not previously known) actually have a complete artery occlusion and studies have shown that if these patients are handled as STEMI (i.e immediate angiography) their mortality is significantly reduced.
Current guidelines therefore recommend that patients with chest pain (or other symptoms suggestive of myocardial ischemia) and a new or presumably new LBBB on ECG should be handled as acute STEMI. However, in the acute phase it is frequently difficult to determine whether the LBBB is new, since prior ECGs may not be available for comparison. Therefore, criteria for ECG diagnosis of acute STEMI in the setting of LBBB have been developed. The Sgarbossa criteria, which have been discussed previously (LBBB and Acute Coronary Syndromes, are considered to be the most useful criteria. The Sgarbossa criteria are presented in Figure 7.
STEMI without ST elevations on ECG
There are situations in which acute transmural ischemia does not cause ST elevations on the 12-lead ECG and these situations are as follows:
- Transmural ischemia located in the posterolateral region of the left ventricle. This is referred to as posterior, or posterolateral, or inferobasal STEMI. It causes ST depressions in leads V1–V3 (occasionally V4); these depressions are reciprocal ST segment depressions, meaning that they mirror the posterior ST segment elevations. The supplementary ECG leads V7, V8 and V9 must be connected to reveal the ST elevations.
- Right ventricular infarction (STEMI): No lead in the 12-lead ECG is adequate to detect right ventricular infarction. Occasionally, ST elevations are seen in V1 and perhaps V2. However, to readily detect ST elevations in patients with right ventricular STEMI, the right sided ECG leads V3R and V4R are required.
Note that Posterolateral (posterior, inferobasal) infarction and right ventricular infarction have also been discussed previously.
Non-significant ST elevations
Transmural myocardial ischemia may occasionally create sufficient ST elevation to meet the criteria in one lead but have slightly less than the required ST elevation in the neighbouring (contiguous) lead. Although the formal criteria for STEMI are not fulfilled in such situations, the patient may still have STEMI. One should always suspect STEMI in patients with chest pain even if the ST elevations are less than required to meet the criteria. The atherothrombotic process is dynamic during the course of STEMI, which implies that the size of the thrombus (and thus the obstruction of blood flow) may vary from one minute to the next. It is wise to perform several ECG recordings (e.g with 5 minute intervals) if the ST elevations do not initially meet the criteria.
Large T-waves occur in several conditions such as hyperkalemia and early repolarization. However, transmural ischemia may cause hyperacute T-waves, which are very large, broad based, symmetric T-waves. Hyperacute T-waves emerge within seconds after the occlusion of a coronary artery and usually resolve within minutes; they are then succeeded by ST elevations. Thus, hyperacute T-wave is actually the first ECG manifestation of STEMI but because these T-waves are short lived it is uncommon to encounter them in clinical practice. Details on T-wave changes in ischemia / infarction has been discussed previously.
Normalization of ECG changes in STEMI
In patients with STEMI the ST-T changes are normalized within days or weeks. QRS changes are mostly permanent, particularly Q-waves. Treatment and reperfusion therapy may modify the speed by which the ECG normalizes in patients with STEMI.
Risk stratification in the acute setting
Risk stratification must always be made in patients presenting with STEMI. Risk stratification is based on patient data and there are numerous risk calculators available. These calculators assist the clinician in estimating the risk of in-hospital mortality, death within 6 months, 12 months and 3 years. Examples of such calculators are FRISC II, TIMI, PURSUIT and GRACE. TIMI and GRACE are the best validated risk calculators and you can find them here:
Management of patients with STEMI
Occlusion of a coronary artery immediately results in ischemia in the myocardium supplied by the artery and its branches. Myocardium may endure approximately 30 minutes of ischemia before the cells die (i.e myocardial infarction). STEMI is is the result of a complete artery occlusion which leads to extensive ischemia and a very high risk of life-threatening ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation). The risk of death is highest in the first hour after symptom onset, which is due to the high risk of ventricular arrhythmias during that phase. Virtually all deaths in the acute phase are due to ventricular arrhythmias, which lead to asystole and ultimately cardiac arrest (Figure 8). Death due to pumping failure (cardiogenic shock) is uncommon in the acute phase.
The first step in the management of patients with STEMI is rapid recognition, since the effects of interventions (antithrombotic therapy, anti-ischemic therapy and reperfusion) are greatest when performed early. The diagnosis is confirmed with the ECG (supplementary leads may be necessary, as discussed above). Presence of significant ST elevations in patients with chest pain (or other symptoms suggestive of myocardial ischemia) is sufficient to diagnose STEMI. All interventions (including reperfusion) may be performed before biomarkers (troponins) are available. Once the diagnosis is confirmed the patient must be continuously monitored (heart rate and rhythm, blood pressure, respiration, consciousness, symptoms, general appearance). A defibrillator must be ready and venous access should be made available immediately.
Note that STEMI is a clinical syndrome (defined by symptoms and ECG) and biomarkers are not necessary to initiate potentially life-saving interventions. Therefore, anti-ischemic and antithrombotic medications should be administered immediately, provided that there are no contraindications. In some instances (discussed below) reperfusion may also be administered without any delay. It is always wise to make a rapid assessment of the probability of aortic dissection before administering drugs that increase bleeding risk.
The clinical examination must include vital parameters (consciousness, heart rate and rhythm, oxygen saturation, blood pressure, respiratory rate), signs of heart failure and pulmonary edema, murmurs (mitral regurgitation, ventricle septum defect). Rapid assessment of bleeding risk should also be performed (discussed below).
Patients with symptoms of ischemia preceeding cardiac arrest should be transported to the catheterization laboratory immediately if circulation returns. Any NSAID (Non-Steroidal Anti-Inflammatory Drug) should be withheld during the acute phase of STEMI because such drugs increase morbidity and mortality (with aspirin being the only exception).
Now follows a review of all evidence-based therapies that may be considered in patients with STEMI.
Oxygen in acute STEMI
Oxygen should be administered if oxygen saturation is <90%. There is no evidence that oxygen affects survival. Randomized controlled trials are currently underway.
There is no data to support or refute any beneficial effect of oxygen in acute STEMI. Randomized controlled trials (comparing oxygen with room air) are underway. Current guidelines recommend oxygen for patients with oxygen saturation <90%. Oxygen is also appropriate for patients with pulmonary edema, heart failure and mechanical complications (free wall rupture, ventricular septum defect, mitral prolapse) of acute STEMI.
Analgesics in acute STEMI
Morphine sulfate is administered to all patients with acute STEMI. Caution is required in patients with hypotension.
Pain activates the sympathetic nervous system which results in (1) peripheral vasoconstriction, (2) positive inotropic effect and (3) positive chronotropic effect. Consequently, sympathetic activity will increase the workload on the heart and thus aggravate the ischemia. This may be detrimental in patients with acute STEMI, which must therefore receive adequate doses of analgesics. Morphine sulfate is the drug of choice; it relieves pain and anxiety. Morphine also causes dilatation of the veins, which reduces cardiac preload. Reduction in preload results in reduced workload on the left ventricle and this may alleviate both ischemia and severity of pulmonary edema.
The required dose of morphine depends on age, BMI and circulatory status. Reduced doses are warranted in patients with hypotension because morphine may cause additional vasodilatation. An initial dose of 2 mg to 5 mg IV may be recommended. This may be repeated every 5 minutes until 30 mg have been administered. Naloxone (0.1 mg IV, may be repeated every 10 minutes) may be administered if there are signs of morphine overdose. Morphine may cause bradycardia which can be countered with atropine 0.5 mg IV (may be repeated as necessary). If large amounts of morphine is insufficient to relieve the pain, one should suspect aortic dissection and ask the patient to reiterate the characteristics of the symptoms.
NSAID (Nonsteroidal anti-inflammatory drugs) and selective cyclooxygenase II (COX-2) inhibitors are contraindicated in acute STEMI (these drugs increase the risk of death in the setting of STEMI).
Note that nitrates and beta blockers also exert analgesic effects (explained below). It is important that the use of morphine does not limit the use of beta blockers, since they potentiate each others negative hemodynamic effect and only beta blockers have been shown to reduce mortality.
Nitrates are administered to the vast majority of patients with STEMI. It does not affect the prognosis but relieves symptoms.
Nitrates cause vasodilatation by relaxing smooth muscle in arteries and veins. The ensuing vasodilatation reduces the venous return to the heart which decreases cardiac preload. This reduces the workload on the myocardium and thus the oxygen demand. Nitrates therefore relieves both ischemic symptoms (chest pain) and pulmonary edema. The vast majority of patients should be offered nitrates.
A dose of 0.4 mg (sublingual or tablet) is given and may be repeated 3 times with 5 minute intervals. Nitroglycerin infusion should be considered if the effect is inadequate (severe angina) or if there are signs of heart failure. Infusion may be initiated with 5 μg/min and titrated up every 5 minutes to 10–20 μg/min. The dose is titrated until symptoms are relieved or a maximal dose of 200–300 μg/min is reached.
Nitrates should not be administered in (1) patients with hypotension, (2) if there is suspicion of right ventricular infarction, (3) sever aortic stenosis, (4) hypertrophic obstructive cardiomyopathy or (5) pulmonary embolism. Administration should proceed with caution if blood pressure drops >30 mmHg from baseline. As with morphine, use of nitrates must not limit the use of beta blockers and ACE inhibitors (these drugs affect blood pressure and heart rate).
A loading dose of aspirin (160 mg to 320 mg) should be given immediately to all patients. Aspirin is given in the prehospital setting and before PCI. Aspirin is then continued indefinitely (maintenance dose 80 mg daily).
A loading dose of a P2Y12-receptor inhibitor should also be given immediately (before PCI). The options include:
- Clopidogrel 600 mg loading dose.
- Prasugrel 60 mg loading dose.
- Ticagrelol 180 mg loading dose.
Clopidogrel is inferior to prasugrel and ticagrelol. Ticagrelol appears to cause less bleeding complications as compared with prasugrel. P2Y12receptor inhibitor is continued for 12 months in patients receiving a stent during PCI. Maintenance doses are clopidogrel 75 mg daily, prasugrel 10 mg daily and ticagrelol 90 mg twice daily.
Note that the interventionist may add additional antiplatelet agents (abciximab, tirofiban, eptifibatide) during PCI. These drugs, however, are not administered outside of the catheterization laboratory.
All patients should immediately be given aspirin (loading dose of 160 to 320 mg) and then continued indefinitely (maintenance dose 80 mg daily). Aspirin is combined with either clopidogrel, prasugrel or ticagrelol.
Aspirin has a remarkable effect: it reduces 30-days mortality by 23%. A loading dose of 160 to 320 mg is indicated in all patients with acute STEMI. Patients who are unable to swallow may be given 300 mg as a suppository or 80 to 150 mg IV. All patients should receive maintenance dose of 80 mg daily which is continued indefinietely. Hypersensitivity to aspirin is uncommon and in that scenario clopidogrel may be used instead. Note that aspirin is a highly effective drug in both the acute setting and in secondary prevention (to prevent re-infarction) and the drug must never be terminated without careful consideration.
Dual antiplatelet therapy (DAPT)
As noted above, optimal antiplatelet effect requires the addition of either ticagrelol, prasugrel or clopidogrel. Combining aspirin with any of these is referred to as DAPT (dual antiplatelet therapy). An individual assessment of bleeding risk is warranted and DAPT should be avoided if the risk is high. DAPT is continued for 12 months in all patients, and the indication is stronger in patients who undergo PCI with placement of stent (both bare metal stents and drug eluting stents).
Addition of clopidogrel to aspirin will additionally reduce mortality by 13%. A loading dose of 600 mg followed by maintenance dose of 80 mg daily is recommended. The additional increase in bleeding risk is smaller with clopidogrel, as compared with prasugrel and ticagrelol.
Prasugrel is more potent than clopidogrel. Prasugrel reduces cardiovascular mortality, non-fatal acute myocardial infarction and stroke more than clopidogrel. Data from randomized trials demonstrate that prasugrel appears to be particularly effective in patients with anterior STEMI. The loading dose is 60 mg followed by maintenance dose of 10 mg daily. Prasugrel is contraindicated in patients with previous stroke, TIA, renal failure and liver failure. Finally, prasugrel should be used with caution in patients older than 75 years as well as those weighing less than 60 kg.
Ticagrelol (loading dose 1080 mg, maintenance dose 90 mg twice daily) is more effective than clopidogrel and reduces cardiovascular mortality, non-fatal acute myocardial infarction and stroke. Although the PLATO study showed that ticagrelol caused more serious bleedings, as compared with clopidogrel, the overall effect was beneficial and it was concluded that the benefits outweighs the risks. In patients referred for primary PCI, ticagrelol is the drug of choice among the three P2Y12-receptor inhibitors.
Patients frequently report dyspnea and, less frequently, bradycardia the first week on ticagrelol treatment. These side effects are benign and usually transient. Ticagrelol is contraindicated in patients with previous cerebral hemorrhage or liver failure (clopidogrel is recommended to those patients instead).
Intravenous antiplatelet agents: Glycoprotein (GP) IIb/IIa receptor antagonists
It may be reasonable to administer intravenous GP IIb/IIIa receptor antagonist in the precatheterization laboratory setting (e.g., ambulance, ED) to patients with STEMI for whom primary PCI is intended.
These agents (abciximab, tirofiban, eptifibatid, elinogrel) blocks the GP IIb/IIIa receptor which is located on the membrane of platelets and connects platelets to fibrinogen and von Willebrand factor. This class of drugs is actually the most potent platelet inhibition available. However, the addition of these agents confer little benefit, which appears to be reserved for certain subgroups of patients. Moreover, GP IIb/IIIa inhibitors have not been evaluated adequately in the era of DAPT. According to the European Society for Cardiology, GP IIb/IIIa antagonists may be considered in the following situations:
- Gp IIb/IIIa antagonists may be considered during PCI if the procedure is not successful (slow or no-reflow) or if angiography shows massive thrombosis or complications of thrombosis.
- Gp IIb/IIIa antagonists may accompany unfractionated heparin (UFH, which then must be dose reduced) if there are no contraindications.
- Gp IIb/IIIa antagonists may be given during transport to high risk patients who are referred to primary PCI.
Anticoagulants in STEMI
Unfractioned heparin (UFH) or bivalirudin is considered in all patients, particularly those undergoing primary PCI.
Unfractionated heparin (UFH), enoxaparin or bivalirudin are anticoagulants which may be given to patients with acute STEMI. Anticoagulation is continued a few days after primary PCI. However, anticoagulants are not necessary thereafter, unless there are other indications (e.g atrial fibrillation).
Low molecular weight heparin (enoxaparin) and unfractionated heparin (UFH) reduce mortality in patients with STEMI. Enoxaparin is given intravenously and is preferred over UFH. If only UFH is available, the loading dose is 70–100 U/kg, given as a bolus. If the patient is also given GP IIb/IIIa antagonists, UFH is reduced to 50–60 U/kg.
Bivalirudin – direct thrombin inhibitor
Bivalirudin was compared with a combination of UHF and GP IIb/IIIa antagonists in the HORIZONS-AMI trial. Bivalirudin caused fewer bleedings and resulted in lower mortality. Hence, bivalirudin is preferred over the combination UFH+GP IIb/IIIa antagonist in patients undergoing primary PCI. Bivalirudin is also preferred in patients with heparin induced thrombocytopenia (HIT), as well as in cases with high risk of bleeding.
Fondaparinux was evaluated in the OASIS-6 study and there were no beneficial effects in patients underoing primary PCI. On the contrary, fondaparinux was associated with increased risk of stent thrombosis.
Beta blockers in STEMI
Beta blockers should be given to all patients in maximal tolerated dosis and continued indefinetely.
Beta blockers have negative inotropic and chronoctropic effect, which reduces heart rate (duration of diastole is therefore prolonged), cardiac output and blood pressure. The workload on the myocardium is reduced and the oxygen consumption and oxygen demand is reduced. Prolongation of diastole will give extra time for the myocardium to be perfused (the myocardium is perfused only during diastole). A large body of evidence demonstrates that beta blockers are very beneficial in patients with STEMI. Beta blockers increase survival, reduce morbidity, improve left ventricular function and may also reduce (or limit) infarct size. Beta blockers presumably also protect against ventricular tachyarrhythmias (ventricular tachycardia).
Treatment with beta blockers should start early (within 24 hours), provided that the patient is hemodynamically stable. Beta blockers may be used in patients with hypertension on presentation.
Metoprolol 5 mg IV may be given three times with 5–10 minutes intervals in the acute setting. Heart rate and blood pressure should be monitored during administration of intravenous beta blockers. If tablets are preferred, metoprolol 25 mg may be given every sixth hour until maximal tolerated dose or 200 mg daily is reached. The dose is limited by bradycardia and hypotension.
Contraindications and caution
Patients with acute heart failure should not be give beta blockers during the acute phase. However, beta blockers should be started early when the heart failure has stabilized. Patients with first-degree AV block should perform a second ECG after administration of beta blockers, since the AV block may progress to higher degrees of AV block. Second-degree and third-degree AV block (without pacemaker) are contraindications. Patients with COPD (chronic obstructive pulmonary disease) should be given beta-1 selective agents (e.g bisoprolol).
Reperfusion in acute STEMI: PCI and fibrinolysis
All patients with acute STMI should immediately undergo angiography with the intention to perform PCI. successful PCI restores blood flow to the ischemic myocardium and halts the infarction process.
Reperfusion refers to the restoration of blood flow (perfusion) in the occluded artery. There are two principal methods for achieving reperfusion in patients with acute STEMI, namely PCI (percutaneous coronary intervention) and fibrinolysis. PCI is by far the most effective method. The term primary PCI refers to PCI performed within 24 hours of symptom onset, whereas secondary PCI refers to PCI performed later than 24 hours after symptom onset. Reperfusion, with either PCI or finbrinolysis, is considered in the following situations:
- Reperfusion should be performed if symptom duration is <12 hours.
- Reperfusion should be considered in patients with symptom duration >12 hours if symptoms and/or ischemic ECG changes persist. Pain is always evidence of ongoing ischemia, which indicates that there is viable myocardium that may be salvaged.
As mentioned above, numerous studies conducted in the past decades have shown that PCI is superior to fibrinolysis. In contemporary practice, fibrinolysis is only administered if it is >120 minutes (from first medical contact) transport to nearest PCI capable hospital. Guidelines recommend the following:
- If a patient arrives to a hospital with catheterization laboratory, the procedure should start within 60 minutes of arrival to hospital (this is called door-to-balloon time).
- If a patient arrives to a hospital without catheterization laboratory, he or she should be relocated to a hospital with such a lab if the procedure can start within 120 minutes from first medical contact.
- If PCI cannot be performed within 120 minutes from first medical contact, then fibrinolysis should be considered. Fibrinolysis should be given within 30 minutes from first medical contact.
- Fibrinolysis should also be considered in patients with symptom duration <2 hours, low bleeding risk, large infarction (per ECG) and time from first medical contact to PCI is >90 minutes.
Fibrinolysis is considered unsuccessful if the magnitude of the ST elevations are not reduced by 50% within 60 minutes. In such cases, PCI (“rescue PCI”) should be considered. In any case, patients arriving to a hospital without catheterization laboratory, should be relocated to a hospital with PCI facility once the patient is hemodynamically stable.
Percutaneous coronary intervention (PCI)
PCI is the most effective mean to restore blood flow in acute STEMI. The vast majority of patients with STEMI are candidates for PCI. Restoration of coronary blood flow is markedly better with PCI, as compared with fibrinolysis (re-flow is greater and the risk of re-stenosis is smaller). PCI is less dependent on symptom duration (fibrinolysis is dependent on symptom duration because the thrombus material reorganizes gradually and becomes less susceptible to fibrinolytic agents).
DAPT should be considered in all patients undergoing primary PCI. Nowadays virtually all procedures include placement of a coronary stent, which may be either drug eluting (DES) or not (bare metal stent, BMS). Data suggests that DES confers lower risk of restenosis.
Fibrinolysis (tenecteplase, alteplase, reteplase) is very effective in lysating a thrombus if it is given early (within 2 hours of symptom onset). The effect of these agents diminish gradually because of a reorganization taking place in the thrombotic material. If fibrinolysis is administered in the prehopsital setting, it may be as effective as PCI. However, fibrinolysis frequently fails to establish a patent blood flow and the risk of reocclusion is significant. Moreover, fibrinolysis may cause serious bleedings and even deaths due to hemorrhage.
Absolute contraindications to fibrinolysis
- Previous cerebral hemorrhage
- Stroke of unknown type
- Ischemic stroke during the past 6 months
- Tumours or injuries in the central nervous system
- Arteriovenous malformation in the central nevous system
- Aortic dissection
- Recent surgery/trauma (within 3 weeks).
- Gastrointestinal bleeding within 4 weeks
- Coagulation disorders
- Lumbal puncture, liver biopsy or similar procuedures within 24 hours.
Relative contraindications to fibrinolysis
- Transient Ischemic Attack (TIA) within 6 months.
- Ongoing oral anticoagulation therapy
- Pregnancy or 1 week post partum
- Refractory hypertenson (systolic blood pressure >180 mmHg and /or diastolic blood pressure >110 mmHg).
- Severe liver disease
- Infectious endocarditis
- Active ulcer
- Prolonged or traumatic resuscitation
Coronary artery bypass grafting (CABG)
CABG has a limited role in the acute phase of STEMI. However, CABG should be considered if (1) PCI fails, (2) if coronary anatomy is not amenable to PCI, (3) if there are mechanical complications (e.g free wall rupture), (4) cardiogenic shock.
- Diagnosis and Management of NSTEMI (Non ST Elevation Acute Myocardial Infarction) and Unstable Angina (UA)
- How myocardial ischemia / infarction affects the ST segment on ECG
- ST elevations in ischemia / infarction and how to differentiate causes of ST elevations
- ST depressions in ischemia / infarction and how to differentiate causes of ST depressions
- How to differentiate various causes of ST segment elevations
- STEMI (equivalents) without ST segment elevations
- T-wave changes (inversion, hyperacute, flat) in ischemia / infarction
- Myocardial ischemia / infarction with ST segment depression
- Left bundle branch block (LBBB) in acute myocardial infarction / ischemia