Myocardial infarction: treatment

Treatment of myocardial infarction is aimed at reducing damage, eliminating ischemia, limiting the infarction zone, reducing the load on the heart and preventing or treating complications. Myocardial infarction is an emergency medical situation, the outcome depends largely on the speed of diagnosis and therapy.

Treatment of myocardial infarction is performed simultaneously with diagnosis. It is necessary to ensure reliable venous access, give the patient oxygen (usually 2 L via a nasal catheter), and begin monitoring the ECG in one lead. Prehospital measures during emergency care (including ECG, chewing aspirin, early thrombolysis performed at the first opportunity, and transport to an appropriate hospital) can reduce the risk of mortality and complications.

Early cardiac marker results help identify low-risk patients with suspected ACS (eg, patients with initially negative cardiac markers and ECG), who can be admitted to a 24-hour observation unit or a cardiac care center. Higher-risk patients should be referred to a unit with monitoring capabilities or a specialized cardiac intensive care unit. There are several accepted risk stratification scales. The Thrombolysis in Myocardial Infarction Risk Score is probably the most widely used. Patients with suspected HSTHM and moderate to high risk should be admitted to a cardiac care unit. Patients with STHM are referred to a specialized cardiac intensive care unit.

For routine continuous monitoring, heart rate, rhythm, and single-lead ECG are useful. However, some clinicians recommend routine multi-lead ECG monitoring with continuous ST segment recording to detect transient ST segment changes. Such symptoms, even in asymptomatic patients, are indicative of ischemia and may help identify high-risk patients who may require more aggressive evaluation and treatment.

Qualified nurses are able to recognize the occurrence of arrhythmia based on ECG data and initiate treatment according to the appropriate protocol. All staff must be able to perform cardiac resuscitation measures.

Concomitant diseases (eg, anemia, heart failure) also need to be actively treated.

The unit for such patients should be quiet, calm, preferably with single rooms; confidentiality of monitoring is essential. Visits and telephone calls to family members are usually limited for the first few days. A wall clock, calendar, and window help the patient to orientate himself and prevent a feeling of isolation, as does the availability of radio, television, and newspapers.

Strict bed rest is mandatory for the first 24 hours. On the first day, patients without complications (eg, hemodynamic instability, ongoing ischemia) and those who have successfully restored myocardial perfusion with fibrinolytic agents or NOVA may sit on a chair, begin passive exercises, and use a bedside table. Walking to the toilet and light paperwork are soon allowed. In case of ineffective restoration of perfusion or complications, patients are prescribed a longer bed rest, but they (especially the elderly) should begin to move as soon as possible. Prolonged bed rest leads to a rapid loss of physical ability with the development of orthostatic hypotension, decreased performance, increased heart rate during exercise, and an increased risk of deep vein thrombosis. Prolonged bed rest also increases the feeling of depression and helplessness.

Anxiety, mood changes, and negative attitudes are common. Mild tranquilizers (usually benzodiazepines) are often prescribed, but many experts believe that such medications are rarely necessary.

Depression develops most often by the 3rd day of illness and (in almost all patients) during recovery. After the acute phase of the disease, the most important task is often to bring the patient out of depression, rehabilitation and implementation of long-term preventive programs. Excessive insistence on rest in bed, inactivity and emphasizing the seriousness of the disease strengthens the depressive state, so patients should be encouraged to sit, get out of bed and start accessible physical activity as soon as possible. The patient should be discussed in detail about the manifestations of the disease, prognosis and individual rehabilitation program.

Maintaining normal bowel function by prescribing laxatives (eg, bisacodyl) to prevent constipation is important. Urinary retention is common in the elderly, especially after several days of bed rest or when atropine is prescribed. Occasionally, a catheter may need to be inserted, but most often the condition resolves spontaneously when the patient gets up or sits on the toilet.

Since smoking is prohibited in the hospital, a hospital stay can help to quit smoking. All caregivers should constantly encourage the patient to quit smoking completely.

Although almost all patients in the acute condition have a poor appetite, tasty food in small quantities maintains a good mood. A light diet (1500 to 1800 kcal/day) is usually prescribed, with sodium intake reduced to 2-3 g. In cases where there are no signs of heart failure, sodium restriction is not required after the first 2 or 3 days. Patients are prescribed a diet low in cholesterol and saturated fats to teach the patient about healthy eating.

Because chest pain associated with myocardial infarction usually resolves within 12 to 24 hours, any chest pain that persists longer or recurs is an indication for further evaluation. It may indicate complications such as ongoing ischemia, pericarditis, pulmonary embolism, pneumonia, gastritis, or ulcer.

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Medicines for myocardial infarction

Antiplatelet and antithrombotic drugs are commonly used to prevent thrombus formation. Anti-ischemic agents (eg, beta-blockers, intravenous nitroglycerin) are often added, especially in situations where chest pain or hypertension persists. Fibrinolytic agents are sometimes used in STMM, but they worsen the prognosis in unstable angina or HSTMM.

Chest pain can be relieved by administering morphine or nitroglycerin. Morphine intravenously from 2 to 4 mg, repeated after 15 minutes if necessary, is very effective, but can depress respiration, reduce myocardial contractility, and is a powerful venous vasodilator. Arterial hypotension and bradycardia after morphine can be treated by quickly raising the arms upward. Nitroglycerin is initially given sublingually, and then, if necessary, it is continued to be administered intravenously by drip.

On admission to the emergency department, most patients have normal or slightly elevated blood pressure. Over the next few hours, blood pressure gradually decreases. If hypertension persists for a long time, antihypertensive drugs are prescribed. Intravenous nitroglycerin is preferred: it lowers blood pressure and reduces the workload on the heart. Severe arterial hypotension or other signs of shock are ominous symptoms and must be treated intensively with intravenous fluids and (sometimes) vasopressor drugs.

Antiplatelet agents

Examples of antiplatelet agents include aspirin, clopidogrel, ticlopidine, and glycoprotein IIb/IIIa receptor inhibitors. All patients are initially given aspirin 160–325 mg (regular tablets, not the rapidly dissolving form) unless contraindicated. They are then given 81 mg once daily for a long period. Chewing the tablet before swallowing accelerates absorption. Aspirin reduces both the short-term and long-term mortality risk. If this drug cannot be prescribed, clopidogrel (75 mg once daily) or ticlopidine (250 mg twice daily) can be used. Clopidogrel has largely replaced ticlopidine because ticlopidine carries a risk of neutropenia, so regular monitoring of white blood cell counts is necessary. Patients with unstable angina or HSTMM who are not planned for early surgical treatment are prescribed acetylsalicylic acid and clopidogrel concomitantly for at least 1 month.

Glycoprotein IIb/IIIa receptor inhibitors (abciximab, tirofiban, eptifibatide) are potent antiplatelet agents administered intravenously. They are most often used with NOVA, especially when stent placement is involved. Results are best when these drugs are administered at least 6 hours before NOVA. If NOVA is not performed, glycoprotein IIb/IIIa receptor inhibitors are reserved for high-risk patients, especially those with elevated cardiac markers, those with persistent symptoms despite adequate drug therapy, or a combination of these factors. These drugs are administered for 24 to 36 hours, and angiography is performed before the end of the administration time. Routine use of glycoprotein IIb/IIIa receptor inhibitors with fibrinolytics is currently not recommended.

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Antithrombotic drugs (anticoagulants)

Low molecular weight heparin (LMWH) or unfractionated heparin are usually prescribed unless contraindicated (e.g., active bleeding or previous use of streptokinase or anistreplase). Either drug can be used in unstable angina and HSTMM. In STMM, the choice depends on the method of restoring myocardial perfusion. When using unfractionated heparin, activated partial thromboplastin time (APTT) monitoring is necessary for 6 hours, then every 6 hours until reaching 1.5-2 times the control time; when prescribing LMWH, APTT testing is not necessary.

Fibrinolytic drugs available in the US

Characteristic	Streptokinase	Nystreplaza	Alteplase	Tenecteplase
Dose for intravenous administration	1.5x10 6 units in 30-60 minutes	30 mg in 5 min	15 mg bolus, then 0.75 mg/kg over the next 30 min (max 50 mg), then 0.50 mg/kg over 60 min (max 35 mg) to a total dose of 100 mg	Calculated by body weight, one-time bolus in 5 seconds: <60 kg-30 mg; 60-69 kg - 35 mg; 70-79 kg - 40 mg; 80-89 kg - 45 mg; > 90 kg - 50 mg
Half-life, min	20	100	6	The initial half-life is 20-24 min; the half-life of the remaining amount occurs in 90-130 min.
Competitive interaction with sodium heparin	No	No	Yes	Yes
Allergic reactions	Yes Expressed	Yes Expressed	Rarely Moderately	Rarely Moderately
Frequency of intracerebral hemorrhages, %	0.3	0.6	0.6	0.5-0.7
Myocardial recanalization rate in 90 min, %	40	63	79	80
Number of lives saved per 100 patients treated	2.5	2.5	3.5	3.5
Cost of a dose	Inexpensive	Expensive	Very expensive	Very expensive

Enoxaparin sodium is the LMWH of choice and is most effective when administered immediately upon arrival at the hospital. Nadroparin calcium and dalteparin sodium are also effective. The properties of hirudin and bivalirudin, new direct anticoagulants, require further clinical study.

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Beta-blockers

These drugs are not prescribed only if there are contraindications (such as bradycardia, heart block, arterial hypotension or asthma), especially in high-risk patients.

Beta-blockers reduce heart rate, blood pressure, and contractility, thereby reducing cardiac workload and oxygen demand. Intravenous administration of beta-blockers in the first few hours improves prognosis by reducing infarct size, recurrence rate, incidence of ventricular fibrillation, and mortality risk. Infarct size largely determines cardiac function after recovery.

During treatment with b-adrenergic blockers, careful monitoring of blood pressure and heart rate is necessary. If bradycardia and arterial hypotension develop, the dose is reduced. Pronounced side effects can be completely eliminated by administering the b-adrenergic agonist isoprotenolum at a dose of 1-5 mcg/min.

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Nitrates

In some patients, the short-acting nitrate nitroglycerin is given to reduce the load on the heart. This drug dilates veins, arteries, and arterioles, reducing the pre- and afterload on the left ventricle. As a result, the myocardial oxygen demand and, consequently, ischemia are reduced. Intravenous nitroglycerin is recommended during the first 24-48 hours in patients with heart failure, previous extensive myocardial infarction, persistent chest discomfort, or hypertension. Blood pressure may be reduced by 10-20 mm Hg, but not below systolic 80-90 mm Hg. Longer use may be indicated in patients with recurrent chest pain or persistent pulmonary congestion. In high-risk patients, nitroglycerin given in the first few hours helps reduce the infarct area and the short-term and possibly long-term mortality risk. Nitroglycerin is not usually prescribed to low-risk patients with uncomplicated myocardial infarction.

Other drugs

ACE inhibitors have been shown to reduce the risk of mortality in patients with myocardial infarction, particularly in anterior myocardial infarction, heart failure, or tachycardia. The greatest effect is seen in patients at highest risk during the early recovery period. ACE inhibitors are given 24 hours or more after thrombolysis; their long-lasting beneficial effect allows for long-term use.

Angiotensin II receptor blockers may be an effective alternative for patients who cannot take ACE inhibitors (e.g. because of cough). They are not currently considered first-line drugs for the treatment of myocardial infarction. Contraindications include arterial hypotension, renal failure, bilateral renal artery stenosis, and allergy.

Treatment of unstable angina and non-ST-segment elevation myocardial infarction

Drugs are given as described above. LMWH or unfractionated heparin may be used. NOVA (sometimes CABG) may also be performed in some patients. Fibrinolytics are not given in unstable angina or HSTHM because the risks outweigh the potential benefits.

Percutaneous coronary artery bypass grafting

Urgent ACE angiography is not usually indicated for unstable angina or HSTHM. However, early ACE angiography (within 72 hours of hospital admission if possible) is indicated in high-risk patients, particularly those with hemodynamic instability, markedly elevated cardiac markers, or both, and in those who remain symptomatic despite maximal medical therapy. This strategy improves outcome, particularly when glycoprotein receptor IIb/IIIa inhibitors are also used. In intermediate-risk patients with ongoing myocardial ischemia, early angiography is useful to identify the nature of the lesion, assess the extent of other changes, and evaluate left ventricular function. This may help determine the potential benefit of ACE or CABG.

Treatment of unstable angina and ST-segment elevation myocardial infarction

Acetylsalicylic acid, beta-blockers and nitrates are prescribed in the same way as described above. Sodium heparin or LMWH is almost always used, and the choice of drug depends on the option for restoring myocardial blood supply.

In STMM, rapid restoration of blood flow to the damaged myocardium by NOVA or fibrinolysis significantly reduces the risk of mortality. Emergency CABG is the best option for approximately 3% to 5% of patients with extensive coronary artery disease (detected during emergency angiography). CABG should also be considered in situations where NOVA fails or cannot be performed (eg, acute coronary artery dissection). When performed by experienced surgeons, CABG in acute STMM has a mortality rate of 4% to 12% and a recurrence rate of 20% to 43%.

Percutaneous coronary artery bypass grafting

Provided that it is performed within the first 3 hours after the onset of myocardial infarction by experienced personnel, NOVA is more effective than thrombolysis and is the preferred option for restoring myocardial blood supply. However, if NOVA cannot be performed within this time interval or there are contraindications to its implementation, intravenous fibrinolytic therapy is used. In some situations, thrombolysis is performed before NOVA with the "light" version of NOVA. The exact time interval in which thrombolysis must be performed before NOVA is still unknown.

Indications for delayed NOVA include hemodynamic instability, contraindications to thrombolysis, malignant arrhythmias requiring pacemaker implantation or repeat cardioversion, and age over 75 years. NOVA after thrombolysis is considered if chest pain or ECG elevation persists or recurs 60 minutes or more after the start of thrombolysis, but only if NOVA can be performed sooner than 90 minutes after symptom recurrence. If NOVA is not available, thrombolysis can be repeated.

After NOVA, especially if a stent is placed, additional therapy with abciximab (a priority inhibitor of IIb/IIIa glycoprotein receptors) is indicated, the duration of which is 18-24 hours.

Fibrinolytics (thrombolytics)

Restoration of myocardial blood supply by thrombolytic drugs is most effective in the first few minutes to hours after the onset of myocardial infarction. The earlier thrombolysis is started, the better. The target time from admission to drug administration is 30 to 60 minutes. The best results are obtained in the first 3 hours, but drugs can be effective for up to 12 hours. However, administration of fibrinolytics by trained emergency personnel before hospitalization can reduce and improve treatment time. When used with aspirin, fibrinolytics reduce hospital mortality by 30 to 50% and improve ventricular function.

Electrocardiographic criteria for thrombolysis include segment elevation in two or more contiguous leads, typical symptoms and new-onset left bundle branch block, and posterior myocardial infarction (tall R wave in V and segment depression in leads V3–V4 confirmed by 15-lead ECG). In some patients, the hyperacute phase of myocardial infarction manifests itself with giant T waves. Such changes are not considered an indication for emergency thrombolysis; the ECG is repeated after 20–30 minutes to determine whether ST segment elevation has appeared.

Absolute contraindications to thrombolysis include aortic dissection, pericarditis, previous hemorrhagic stroke (at any time), previous ischemic stroke within the previous year, active internal bleeding (not menstrual), and intracranial tumor. Relative contraindications include blood pressure greater than 180/110 mmHg (while receiving antihypertensive therapy), trauma or major surgery within the previous 4 weeks, active peptic ulcer, pregnancy, bleeding diathesis, and hypocoagulable state (INR > 2). Patients who have received streptokinase or anistreplase should not be re-administered these drugs.

Tenecteplase, alteplase, reteplase, streptokinase, and anistreplase (non-isolated plasminogen activator complex), administered intravenously, are plasminogen activators. They convert single-chain plasminogen to double-chain plasminogen, which has fibrinolytic activity. The drugs have different characteristics and dosing regimens.

Tenecteplase and reteplase are the most recommended, since tenecteplase is administered as a single bolus over 5 seconds, and reteplase - as a double bolus. Reducing the duration of administration leads to a reduction in the number of errors compared to other fibrinolytics that have a more complex dosing regimen. Tenecteplase, like alteplase, has a moderate risk of intracranial hemorrhage, a higher rate of restoration of vascular patency compared to other thrombolytics, but are expensive. Reteplase creates the greatest risk of intracerebral hemorrhage, the rate of restoration of vascular patency is comparable to tenecteplase, the cost is high.

Streptokinase may cause allergic reactions, especially if it has been administered previously, and its administration time is 30 to 60 minutes; however, this drug has a low risk of intracranial hemorrhage and is relatively inexpensive. Anistreplase has a similar incidence of allergic complications compared to streptokinase, is slightly more expensive, but can be administered as a single bolus. Neither drug requires concomitant administration of sodium heparin. The rate of vessel patency restoration for both drugs is inferior to other plasminogen activators.

Alteplase is administered in an accelerated version or by continuous administration up to 90 minutes. Combined administration of alteplase with intravenous sodium heparin increases the effectiveness, is non-allergenic and has a higher rate of restoration of vessel patency compared to other fibrinolytics, but is expensive.

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Anticoagulants

Intravenous administration of unfractionated heparin or LMWH is prescribed to all patients with STMM, except those who are administered streptokinase or alteplase, and if there are other contraindications. When sodium heparin is prescribed, APTT is determined after 6 hours and then every 6 hours until the indicator increases by 1.5-2 times compared with the control. LMWH does not require determination of APTT. The administration of the anticoagulant can be continued for more than 72 hours in patients with a high risk of thromboembolic complications.

LMWH enoxaparin sodium used with tenecteplase has the same efficacy as unfractionated heparin and is cost-effective. No large studies have been conducted on the combined use of enoxaparin sodium with alteplase, reteplase, or CHOVA. The first subcutaneous administration is performed immediately after the intravenous one. Subcutaneous administration is continued until revascularization or discharge. In patients over 75 years of age, the combined use of enoxaparin sodium and tenecteplase increases the risk of hemorrhagic stroke. For these patients, unfractionated heparin is preferable in a dose calculated according to the patient's body weight.

The use of intravenous sodium heparin with streptokinase or alteplase is currently not recommended. The potential benefits of subcutaneous sodium heparin compared with no thrombolytic therapy are unclear. However, in patients at high risk of systemic embolism [eg, previous massive myocardial infarction, presence of LV thrombi, atrial fibrillation (AF)], intravenous sodium heparin reduces the incidence of potential thromboembolic events.

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