Treatment of myocardial infarction: features of drug therapy

Myocardial infarction (MI) is an acute condition in which necrosis of cardiomyocytes is observed against the background of impaired coronary circulation. The larger the area of necrosis, the heavier the clinic and the adverse consequences. That is why it is extremely important that the patient is provided with prompt medical assistance.

As a rule, the initial therapy of acute MI is aimed at restoring the perfusion of the heart muscle to save as much as possible at risk myocardium. This can be achieved with the help of pharmacological or mechanical means, such as percutaneous coronary intervention (PCI) or aorto-coronary bypass (CABG).

The morbidity and mortality from MI are significantly reduced if patients and nearby people with them early recognize the symptoms and activate the emergency medical care system. This significantly reduces the time until the final treatment.Trained prehospital staff can provide vital interventions if the patient develops cardiac arrest. The key to improving survival is the availability of early defibrillation.

Video: Myocardial infarction. Symptoms, Symptoms and Methods of Treatment

Pre-hospital care and treatment

In the presence of pain in the chest, it is necessary to treat the patient as if this sign indicates the ischemic origin of the disease, unless precise proof of the opposite is established. If possible, hospitalization of patients with hemodynamic instability or respiratory failure is performed.

Specific prehospital care includes the following:

• Intravenous access, additional oxygen, if oxygen saturation is less than 90%, pulse oximetry.
• Immediate use of aspirin.
• The intake of nitroglycerin to eliminate severe chest pain is taken sublingually or in the form of a spray.
• Telemetry and prehospital electrocardiography (ECG), if any.

Most of the deaths caused by myocardial infarction occur early and are associated with primary ventricular fibrillation.Therefore, the initial tasks are immediate ECG monitoring; electrical cardioversion in cases of fibrillation; and rapid transmission of the patient to facilitate diagnosis of the condition of the coronary arteries.

Additional goals of prehospital treatment include:

• adequate analgesia (usually achieved with morphine);
• pharmacological reduction of excessive sympathoadrenal and vagal stimulation;
• treatment of hemodynamically significant or symptomatic ventricular arrhythmias (usually with amiodarone and lidocaine);
• maintenance of cardiac output, systemic arterial pressure and respiration.

Prehospital fibrinolytic therapy by the introduction of a tissue type plasminogen activator, aspirin and heparin can be prescribed to patients with benign MI, while electrocardiographic data should be used. Appointed within 90 minutes after the onset of symptoms. This treatment improves the results, compared to thrombolysis, started after the patient arrived at the hospital .

Prehospital fibrinolytic therapy is not widely used in the United States due to a lack of resources for training prehospital therapists or lack of funding for the necessary equipment. However, it is common in some regions of Europe and the UK.In the domestic conditions of medical care this method of treatment is so rarely used.

Later, after the patient's admission to the profile clinic, the myocardial infarction is treated, taking into account the existing requirements. In particular, there are differences in the conduct of drug therapy in patients with ST segment elevation and without it.

Treatment of myocardial infarction with ST elevation

The key components of such therapy are rapid recognition of the symptoms of the disease and timely reperfusion. The greatest emphasis is placed on the proper and timely use of any form of reperfusion therapy.

Reperfusion

Pharmacological reperfusion should be performed as soon as possible, most optimally within 12 hours after the onset of symptoms and who have a persistent increase in the ST segment. In addition, an early reperfusion strategy has recently been considered in patients who appear after more than 12 hours, provided there are clinical and / or ECG signs of ongoing ischemia.

Fibrinolytic therapy

Fibrinolysis is an important part of reperfusion strategy. The advantage of fibrinolytic therapy in patients with MI and the elevated ST segment is already well known, with the greatest effect on early use (within 12 hours after the onset of the disease) and in patients with the highest cardiovascular risk, including patients older than 75 years .

Fibrinolytic therapy may be ineffective in patients in whom the clinic is observed for more than 12 hours from the onset of symptoms, although current recommendations consider fibrinolysis in patients with symptoms of extensive myocardium at risk (based on ECG or cardiovascular imaging) or hemodynamic instability, especially if not available other methods of treatment.

Absolute contraindications to fibrinolytic therapy in patients with AI and ST segment elevation:

• Any previous intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known intracranial neoplasms (primary or metastatic)
• Ischemic stroke in the last 3 months (except for an acute stroke within 4.5 hours)
• Anticipated dissection of the aorta
• Significant head or face trauma for 3 months
• Intracranial or intraspinal surgery for 2 months
• Severe uncontrolled hypertension (not responding to emergency therapy)

Relative contraindications for fibrinolysis:

• The presence of chronic, severe, poorly controlled hypertension
• Determination of systolic pressure> 180 mm Hg. Art. or diastolic pressure> 110 mm Hg. Art.
• History of a previous ischemic stroke> 3 months
• Dementia
• Traumatic or prolonged cardiopulmonary resuscitation (> 10 minutes)
• Recent (within 2-4 weeks) internal bleeding
• Pregnancy
• Active peptic ulcer disease
• Current use of anticoagulants

Preparations used during fibrinolysis:

• Non-fibrin-specific: streptokinase
• Fibrin-specific: tenecteplase, reteplase, alteplase

Anticoagulant therapy

Anticoagulants are an important adjuvant therapy for reperfusion, regardless of the strategy chosen.

In the primary treatment, unfractionated heparin, bivalirudin and low molecular weight heparin (eg, enoxaparin) are used. Fonparinux is not used in this situation because of the increased risk of catheter thrombosis.

Patients receiving fibrinolytic therapy should be prescribed an anticoagulant before revascularization. If reperfusion is not possible, anticoagulants should be prescribed for at least 48 hours or for a period of 8 days in the hospital. It is important to use caution when prescribing enoxaparin for patients over 75 years of age, as well as for kidney dysfunction, since the use of enoxaparin is associated with a higher risk of intracranial hemorrhage. Bivalirudin may be administered to patients who have heparin-induced thrombocytopenia or require anticoagulation.

Antiaggregants

All patients with MI and ST segment should receive an empirical loading dose of aspirin (150.5 to 325 mg) as early as possible and before reperfusion, regardless of the method of reperfusion therapy. The daily maintenance dose (75 to 81 mg) is usually administered to all patients after myocardial infarction.

Other antiplatelet agents used for dual antiplatelet therapy are P2Y12 receptor inhibitors (eg, clopidogrel, ticagrelor, prasugrel). The loading dose of these drugs is administered before or during reperfusion, and then a maintenance dose is applied for a long time.

During fibrinolytic therapy, a loading dose of clopidogrel 300 mg should be used, followed by a daily maintenance dose of 75 mg for at least 14 days.

Other antiplatelet agents that can be used to treat myocardial infarction are intravenous glycoprotein antagonists. In the preparation of bivalirudin as the main anticoagulant, GP IIb / IIIa inhibitors can additionally be used.

Treatment of myocardial infarction without ST elevation

Key points in the treatment of patients with acute coronary syndrome without the ST segment are an early assessment of hemodynamic and electrical stability, as well as the overall risk in these patients.

There are two alternative therapies:

• Early invasive strategy with angiography, for the purpose of revascularization with percutaneous coronary intervention or aorto-coronary bypass
• Conservative strategy with initial drug therapy and non-invasive cardiovascular visualization.

Regardless of the chosen strategy, the aggressive utility of such drugs as anticoagulants, antiaggregants, beta-blockers, statins and the possible use of angiotensin converting enzyme inhibitors for the respective groups of patients is usually used.

Beta-blockers

Acted by reducing the oxygen consumption of the myocardium, which leads to a decrease in heart rate, blood pressure and myocardial contractility. They also play an important role in reducing the risk of recurrent myocardial infarction and complicated ventricular arrhythmias. These drugs are recommended for oral administration within the first 24 hours, preferably using one of three drugs that have proven effective in reducing the mortality of patients with heart failure: metoprolol, carvedilol or bisoprolol.

Beta-blockers should not be administered intravenously to patients with a low cardiac output (heart rate> 110 beats / min or systolic blood pressure <81). These agents should also not be given to patients who have a contraindication to beta blockers (for example, a cardiac unit of the first degree with a PR interval of> 240 ms, a cardiac block of the second or third degree without a pacemaker, severe / active / reactive airway disease).

For patients with chronic obstructive pulmonary disease or chronic asthma, beta-1-blockers are preferably administered and should be started with low doses.

Calcium channel blockers

Calcium channel blockers without dihydropyridine (for example, verapamil or diltiazem) should be prescribed for relapsing myocardial ischemia only in case of contraindications to the use of beta-blockers.

Like beta blockers, the use of calcium channel blockers without dihydropyridine can also increase the likelihood of developing cardiogenic shock, so extreme care should be taken when considering the use of these drugs.

Short-acting nifedipine is not assigned to patients who do not receive beta-blockers, as this can lead to an increased risk of mortality in patients with ACS.

Antiaggregants

• Aspirin

The initial dose varies from 150 to 325 mg. The drug should be given to all patients with MI without ST elevation as soon as possible after the onset of the attack. Next, a maintenance dose of aspirin at 75-100 mg per day, which is used for life.

Some clinical data suggest that a maintenance dose of aspirin above 160 mg per day is associated with an increased risk of bleeding without a clear improvement in performance.

P2Y12 Receptor Inhibitors

Their use in addition to aspirin resulted in better results with a reduction in the incidence of cardiovascular death, myocardial infarction, and stroke. Three P2Y12 receptor inhibitors, most commonly used to treat MI without ST segment, described the following drugs:

• Clopidogrel
• Tikagrelor
• Prasugrel

All three medicines are prescribed at the initial dose, and then a daily maintenance treatment of up to 12 months is performed for all patients with early invasive or conservative exposure strategies.

• Clopidogrel

An initial dose of 300-600 mg is recommended, followed by a maintenance dose of 75 mg per day.

• Tikagrelor

The drug has a faster initial effect and a short half-life, compared with clopidogrel; so it is used twice a day. The recommended loading dose is 180 mg, followed by a maintenance dose of 90 mg twice daily.

The unique side effect observed in patients taking ticagrelor is shortness of breath, but this manifestation is rarely serious enough to lead to discontinuation of treatment.

Ticagrelor should not be used concomitantly with higher doses of aspirin (> 100 mg per day).

• Prasugrel

The recommended loading dose is 60 mg, followed by a maintenance dose of 10 mg per day.

Because of the unique ways of metabolism, he has a faster and more stable inhibition of platelets than clopidogrel. The main contraindication to the use of prasugrel is a previously experienced stroke or transient ischemic attack, age over 75 years and low body weight (78 kg and below).

Future and Developing Therapy

Local injection of progenitor cells, growth factors, or stem cells can stimulate vascular development. Stem cell therapy in patients with acute myocardial infarction remains the main goal of the study, with some data showing modest results.

Researchers in the field of reinfusion of enriched progenitor cells and remodeling infarction in acute myocardial infarction examined 204 patients with acute myocardial infarction and ST elevation and reported a significant improvement in the left ventricular ejection fraction among patients who received intracoronary progenitor cells than placebo.

Several small clinical trials have shown that intracoronary delivery of mononuclear cells from the autologous bone marrow improves left ventricular function when administered within the first week after MI. However, the results of a randomized LateTIME trial in which the intracoronary delivery of mononuclear cells was assessed delivered 2-3 weeks after the first MI of improved global and regional left ventricular function compared with placebo suggested a slight improvement in this strategy in patients with MI and left ventricular dysfunction after reperfusion with percutaneous coronary intervention. [1 - Traverse JH; Henry TD; Ellis SG; Pepine CJ; Willerson JT; Zhao DX; Forder JR; Byrne BJ;Hatzopoulos AK; Penn MS; Perin EC; Baran KW; Chambers J; Lambert C; Raveendran G; Simon DI; Vaughan DE;Simpson LM; Gee AP; Taylor DA; Cogle CR; Thomas JD; Silva GV; Jorgenson BC; Olson RE; Bowman S; Francescon J; Geither C; Handberg E; Smith DX; Baraniuk S; Piller LB; Loghin C; Aguilar D; Richman S; Zierold C; Bettencourt J;Sayre SL; Vojvodic RW; Skarlatos SI; Gordon DJ; Ebert RF; Kwak M; Moyé LA; Simari RD. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA. 2011; 306 (19): 2110-9]

Video: Health. The American project. Treatment of myocardial infarction. (10/01/2017)