RU2554756C1 - Method for rehabilitation of elderly patients with ischemic heart diseases accompanied by chronic heart insufficiency following myocardial infarction - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns rehabilitation of elderly patients with ischemic heart disease (IHD) accompanied by chronic heart insufficiency (CHI) following myocardial in myocardial infarction (MI). That is ensured by administering Omacor, a preparation of omega-3-polyunsaturated fatty acids in the remote period, 6 or more months after the suffered MI with underlying a standard drug therapy 60 minutes before the graduated walking.

EFFECT: this complex of the drug preparations combined with the graduated physical exercises provides higher tolerance to physical exercises, improving the cardiovascular function and normalising the lipid exchange that in turn leads to reducing a number of unfavourable cardiovascular episodes and delaying CHI.

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Description

The invention relates to medicine and can be used in cardiology and rehabilitation for the physical rehabilitation of elderly patients who have had myocardial infarction (MI).

Modern management tactics for patients with coronary heart disease (CHD), weighed down by chronic heart failure (CHF), includes physical rehabilitation. According to a number of clinical studies, as well as a meta-analysis of ExTr-MATSN, dosed physical activity has a positive effect on the prognosis of patients with heart failure [1]. According to the results of a meta-analysis of ExTr-MATSN among patients who trained during the year, mortality decreased by 35%, based on which physical training was assigned to class I recommendations (level of evidence B) for the diagnosis and treatment of heart failure [2].

However, many issues relating to the training of such patients (the timing of the start of training, duration, background drug therapy) remain unresolved; in other words, the optimal cardiorehabilitation programs for elderly heart failure patients after MI have not yet been determined [3, 4]. In particular, according to Nikolaeva L.F., Aronova D.M. patients who have undergone myocardial infarction are allowed to start prolonged physical activity 3-4 months after it [5], but there is no consensus regarding the timing of physical rehabilitation in elderly patients with coronary heart disease who have had myocardial infarction. Moreover, the progression of heart failure is determined by the rate of post-infarction myocardial remodeling, which can last for weeks or months, but, according to Perutsky D.N. et al. (2011) by the 6th month after MI, the lack of progression of CHF due to the completed remodeling processes becomes apparent, or in the future after the transferred MI, CHF will take on a fast or moderate progressive character [6].

In the Russian Federation, currently about 25% of the population are over 65 years of age, which, in accordance with the documents of the UN and the International Labor Organization, are considered to be elderly persons [7]. Patients of older age groups are prone to a complicated course of myocardial infarction and often have aggravated comorbidity. As a method of early rehabilitation in patients with coronary artery disease who have undergone myocardial infarction, in the hospital schemes of group and individual physiotherapy exercises are offered that have repeatedly shown their effectiveness and positive prognostic effect, however, in older age groups, group rehabilitation is unacceptable, and individual training is impossible due to organizational and economic difficulties [7].

There is a method of rehabilitation of elderly patients with heart failure who have undergone MI, at the sanatorium stage of rehabilitation, in which to reduce the risk of recurring cardiovascular catastrophes and improve the quality of life of patients, a complex of physical training is used using an exercise bike and dosed walking under the control of central hemodynamics [8] .

This method is the closest to the claimed technical essence and the achieved clinical result and is selected as a prototype.

The disadvantage of this method is that the effectiveness of controlled training is limited by the presence of uncorrected circulatory hypoxia in heart failure after MI, in addition, it is also applicable only to the short sanatorium phase of rehabilitation of elderly patients who have had myocardial infarction, due to the need to use special technical devices, such as an exercise bike, which severely limits the use of this method of patients at home.

The objective of the invention is to increase the efficiency of the method of rehabilitation of elderly patients in the long term after the transferred MI.

The problem is solved by appointing in a long time (after 6 months or more) after myocardial infarction with coronary heart disease associated with chronic heart failure, against the background of standard drug therapy 60 minutes before the start of controlled physical training by means of a dosed walking antioxidant - omega-3- polyunsaturated fatty acids (ω-3 PUFAs) - Omacor.

New in the proposed method is the appointment of elderly patients with coronary artery disease with CHF 6 months or more after the MI of the drug ω-3 PUFA Omacor 60 minutes before the start of controlled physical training in the form of a dosed walk.

The proposed rehabilitation method is based on the fact that it is based on the effect of ω-3 PUFAs on such triggering factors for the development of chronic heart failure in patients with myocardial infarction, such as diastolic and systolic myocardial dysfunction and hypertensive left ventricular hypertrophy, which ultimately provides regression ischemic myocardial dysfunction, will reduce the total number of adverse cardiovascular events [9]. In particular, studies of Green R. (2007) and Arena R. (2008) showed that in patients with coronary artery disease with CHF, a decrease in pumping function of the heart after myocardial infarction is associated with a decrease in peak oxygen consumption by the myocardium of the heart and the body as a whole, which is an independent predictor of cardiac death and adverse cardiovascular events [10, 11]. According to the GISSI-HF study, it was found that the appointment of Omacor in patients with coronary artery disease with CHF provided a significant decrease in overall mortality by 9% and hospitalization rate due to cardiovascular causes by 8% during 90 days of treatment, but did not affect on the prognosis of patients after AMI [8, 12, 13]. At the same time, in a meta-analysis of Poole CD. et al. (2013) presented that the administration of ω-3 PUFAs in the first 14 days. after AMI leads to a statistically significant reduction in the risk of death by 32% in the first 90 days. - by 22%, but the initiation of therapy with ω-3 PUFA in more than 90 days. after transferred AMI practically does not affect the prognosis [14]. In addition, Piepoli M.F. et al. (2004) found that the use of physical training in patients with coronary artery disease associated with severe functional classes of heart failure can reduce not only the number of adverse cardiovascular events, but also improve the quality of life of patients [1]. However, data on the use of Omacor in elderly patients with coronary artery disease and heart failure who have undergone myocardial infarction are not enough, and such patients, as a rule, were not included in long-term rehabilitation programs, including physical training.

The technical result of the invention is to increase the efficiency of the method of rehabilitation of elderly patients with ischemic heart disease with chronic heart failure who have undergone myocardial infarction, which will improve the quality of life and reduce the risk of adverse cardiovascular events.

The technical result is achieved by appointing in a long time (after 6 months or more) after myocardial infarction for elderly patients with coronary heart disease with chronic heart failure while conducting controlled physical training Omacor antioxidant in addition to the main therapy. This makes it possible to provide more effective and safer approaches to carrying out rehabilitation measures in elderly patients with coronary heart disease who have undergone myocardial infarction by implementing: 1) protecting the myocardium from the toxic effects of peroxidation, reducing the death of cardiomyocytes (necrosis and apoptosis pathways); 2) anti-ischemic action - improving both systolic and diastolic functions of the left ventricular myocardium; 3) reduction of endothelial damage under the influence of stressful hemodynamic effects.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. No identical set of features was found in the analyzed literature. The present invention can be used in healthcare.

Based on the foregoing, it should be considered that the invention meets the conditions of patentability "Novelty", "Inventive step", "Industrial applicability".

The method is as follows.

Before starting treatment, exercise tolerance is determined by a bicycle ergometry test (VEM). To do this, the test is performed with a pedaling speed of 60 revolutions per 1 minute, with a stepwise, continuously increasing load, starting from 25 W with a subsequent minute-by-minute increase in the load by 10 W until the criteria for stopping the sample, such as:

- the appearance or intensification of angina pectoris of moderate and severe intensity;

- pallor of the skin, cyanosis (signs of hypoperfusion);

- stable ventricular tachycardia;

- ST rise of 1 cm or more (except for VI and aVR);

- ST segment depression> = 4 mm;

- increasing chest pain;

- achievement of the estimated maximum or submaximal heart rate.

6 months after myocardial infarction, while taking standard therapy, including taking aspirin at a dose of 75 mg / day, ACE inhibitors (enap - at a dose of 5 to 40 mg / day, selected individually), diuretic (hypothiazide - at a dose of 12, 5 to 75 mg / day, selected individually), α1β1β2-blocker (carvedilol - at a dose of 6.25 to 50 mg / day, selected individually) 60 minutes before the start of controlled physical training (dosed walking), the patient takes Omacor 1 time per day throughout life.

Then the patient performs dosed walking, starting from 0.5 km at a pace of walking of 70 steps per minute to 2 km at a pace of 100-110 steps per minute at a distance of 2 to 10 km, while the patient himself controls the distance and speed of walking, based on its satisfactory condition, the absence of anginal attacks, and the fact that the heart rate should be no more than 60% of the maximum established by the results of VEM. Every 3 months, the patient’s physical condition is monitored using a VEM sample, and if necessary, the level of physical activity is corrected (based on the obtained VEM results).

68 patients with ischemic heart disease with chronic heart failure were examined 6 months or more after history of myocardial infarction (39 men and 28 women) aged 60 to 77 years (mean age 65.3 ± 6.8 years). Two groups were formed by simple randomization: a group of physical training against the background of taking Omacor (according to the proposed method) - 35 patients (group "Omacor + training") while taking aspirin at a dose of 75 mg / day, α1β1β2-blocker carvedilol (in a dose starting from 6.125 mg / day in two doses, followed by its increase to the maximum tolerated (average 19.6 ± 5.4 mg / day), and ACE enap (in a dose starting from 5 mg / day to a maximum dosage of 40 mg / day ) and a hypothiazide diuretic (in a dose starting from 12.5 mg / day to a maximum dosage of 75 mg / day) and the comparison group without using the proposed method - 33 patients.

For each patient, a specially designed clinical chart was filled out. All patients gave their written informed consent to participate in the study. The condition of the patients was evaluated at baseline and after 6 months with an analysis of the frequency of the combined endpoint, including: mortality, stroke, repeated hospitalizations for exacerbations of heart failure, repeated MI. In addition, systolic function of the left ventricle was evaluated (according to ECHO KG) and physical tolerance according to the 6-minute walk test. Additionally, the lipid spectrum of the blood was evaluated.

The criteria for evaluating the good anti-ischemic and hemodynamic effects of the proposed method were considered to be: regression of CHF symptoms, a decrease in the frequency and severity of angina pectoris, a decrease in the daily requirement of nitrates, an increase in physical tolerance based on the result of the 6-minute walk test.

The study included patients whose condition remained stable for at least 2–3 weeks on constant basic therapy, including a disaggregant, an ACE inhibitor, β-blocker, a statin, a diuretic, and, if necessary, an aldosterone antagonist.

At the time of inclusion in the study, patients of both groups did not differ in such basic indicators as age, gender, concomitant pathology, severity of circulatory failure, received drug therapy. After randomization, patients of the study group in addition to standard therapy received a complex of physical rehabilitation according to the proposed scheme and the drug Omacor.

Statistical analysis of the obtained digital data was performed using the STATISTICA 6.0 software (StatSoft, USA).

The results of observation of patients of the studied groups after 6 months are presented in table 1. In the group of patients receiving Omacor, against the background of controlled training, significantly fewer deaths, strokes and repeated myocardial infarction were diagnosed. At the same time, in the studied group of hospitalizations, repeated hospitalizations due to decompensation of heart failure and adverse cardiovascular events were statistically significantly less likely (11.4% vs 30.3%, p = 0.029; 25.7% vs 57.6%, p = 0.015 respectively).

Table 1
The frequency of development of the combined endpoint in the study groups after 6 months of observation Indicators Comparison Group (n = 33) Group “Omacor + training” (n = 35) R Cardiovascular death 3 (9.1%) - 0.217 Myocardial infarction 5 (15.2%) 2 (5.7%) 0.378 Stroke 1 (3.0%) - 0.976 Hospitalization with decompensation of CHF 10 (30.3%) 4 (11.4%) 0.029 Total number of adverse cardiovascular events 19 (57.6%) 6 (17.1%) 0.001

According to ECHO-KG data, it was found that in the group of physical training with Omacor intake, a significant (by 20.4%, p = 0.001) increase in the LV ejection fraction and a clear (by 11.7%, p = 0.001) decrease in the final systolic volume were achieved LV. In the same group, there was a significant increase in exercise tolerance and a decrease in the number of angina attacks per week - by 33.8% (p = 0.001) (table 2).

In addition, a significant anti-atherogenic effect of the proposed technique was revealed, namely: a decrease in the level of total blood cholesterol by 23% (p = 0.001), a decrease in the content of atherogenic low-density lipoproteins (LDL) and triglycerides by 23 and 28% (p = 0.001), respectively. an increase in the content of antiatherogenic high-density lipoproteins (HDL) - by 11.6% (p = 0.001) (table 3).

Thus, after 6 months or more after myocardial infarction, taking 60 minutes before the start of controlled physical training of the antioxidant drug ω-3 PUFA - Omacor against the background of standard drug therapy for elderly patients with coronary heart disease with chronic heart failure allowed us to ensure a significant reduction in the frequency of repeated hospitalizations about the progression of heart failure and the total number of adverse cardiovascular events. In addition, a significant improvement in the clinical course of IHD and CHF was recorded: fewer angina attacks per week, improved exercise tolerance and improved systolic function of the heart. No negative coronary or hemodynamic effects have been established.

The proposed method for the rehabilitation of elderly patients with coronary heart disease with chronic heart failure who have had MI is illustrated by the following clinical examples.

Example 1 (2013). Patient K., 67 years old, was admitted as planned to the therapeutic department with a diagnosis of IHD: angina pectoris II FC. Postinfarction (2009) cardiosclerosis. NK IIA. CHF FC III (NYHA).

Upon admission, he complained of shortness of breath as "lack of air" with little physical exertion, general weakness, and a rapid heartbeat.

Objectively: the general condition of a patient of moderate severity due to decompensation of heart failure. The position is active. The physique is correct. The constitution is normostenic. The food is normal. The skin is clean, normal humidity, pale, diffuse cyanosis. Lymph nodes are not enlarged. Trophic changes in both legs (induction). Varicose veins of n / extremities. Musculoskeletal system without visible changes. Number of respiratory movements 20 per minute. The rhythm is correct. Breathing through the nose is free. Veins of the neck are not dilated. Percussion sound over the lungs is clear, pulmonary. Vesicular breathing with a harsh tint. A small amount of dry rales was heard. The area of the heart is not changed. The apical impulse in the V intercostal space along the mid-clavicular line. A cardiac impulse is not detected. Heart sounds are deaf. The heart rate is correct. Heart rate of 85 beats per 1 minute. In a clinical blood test, signs of mild anemia (HB 117 g / l, er 3.98 × 109 / l). In the clinical analysis of urine without pathological changes. When ECHO KG study, a slight expansion of the LV cavity. Hypo- and akinesis of the apex. LVEF 46%, Aorta compacted - 36 mm (Table 4).

Table 4
Indicators of ECHO KG and lipid spectrum of patient K. Indicators Hospital stage 3 months ECHO-KG KDR LV (cm) 6.2 5.7 DAC LV (cm) 4.67 4.2 LP (cm) 4.1 4.1 MZHP (cm) 1,2 1,1 WLW (cm) 1,2 1,1 PV (%) 46 51 Lipid spectrum OXS (mmol / L) 6.7 5,4 TG (mmol / L) 1.4 1,0 LDL (mmol / L) 4.63 3.8 HDL (mmol / L) 1,02 0.8

In the hospital, therapy was prescribed: bisoprolol 5 mg, enalapril 2.5 mg × 2 times a day, morning and evening; aspirin-cardio 100 mg at lunch, float 75 mg in the morning, veroshpiron 25 mg × 4 times a day, atorvastatin 40 mg at night. To individually selected doses of drugs from the first day of hospitalization, an omega-3 fatty acid preparation (Omacor) was added at a dose of 1000 mg / day. By the time the patient was discharged from the hospital, according to the ECHO data, positive dynamics was recorded in the form of an increase in the PV indicator of 51% (by 10.9%). 10 days after discharge from the hospital, a VEM test was performed as planned: TFN - 75 W, submaximal heart rate reductions - 98 beats per minute. Further, the patient was recommended to conduct dosed walking from 0.5 km at a walking pace of 70 steps per minute to 2 km at a pace of 100-110 steps per minute at a distance of 2 to 10 km, while he himself must control the distance and speed of walking based on from its satisfactory condition, the absence of anginal attacks, and the fact that the heart rate should be no more than 60% of the maximum set. After 3 months with repeated VEM, a positive dynamics was revealed in the form of an increase in TFN to 125 W and an increase in submaximal heart rate from 98 beats. per minute up to 116 beats. per minute.

EXAMPLE 2 (2013). Patient D., 71 years old, senior citizen. He entered the therapeutic department with a diagnosis of coronary heart disease: exertional angina II FC. Postinfarction (2012) cardiosclerosis. Paroxysmal form of AF. Rare supraventricular extrasystole. Paroxysmal supraventricular tachycardia. NK II A, CHF FC III (NYHA). Hypertension III Art. Risk 4.

Upon receipt of a complaint about an increase in blood pressure to 170/90 mmHg, accompanied by dizziness, headache, shakiness when walking, and a decrease in concentration of attention; for shortness of breath by the type of "lack" of air with a slight fn - torso, self-care; cough, without sputum, "whistles" in the chest, swelling of the legs. Real deterioration in well-being in the form of the above complaints within a week.

Objectively: a state of moderate severity due to decompensation of heart failure. The position is active. The physique is correct. The constitution is normostenic. Nutrition increased. Consciousness is clear. The skin is clean, normal humidity. Lymph nodes - b / o. The thyroid gland is not palpable. The musculoskeletal system is not visually changed. Percussion above all pulmonary fields clear pulmonary sound. Breathing in the lungs is vesicular, weakened along the posterior surface of the chest from two sides, no wheezing. Respiratory rate 19 per minute. Digestive organs: tongue moist, clean. The abdomen on palpation is soft, painless. The liver is palpated. (+) 4-5 cm from under the costal arch, the edge is smooth, pointed, slightly painful, tightly elastic. Bubble symptoms are negative. Chair - daily decorated. The area of the heart is not changed. The apical impulse in the V intercostal space is 1 cm medially from the mid-clavicular line. A cardiac impulse is not detected. Heart sounds are rhythmic, muffled. There is no noise. HELL 150/70 mm Hg; heart rate of 80 per minute. Genitourinary system: the lumbar region is not visually changed. The kidneys are not palpable. See striking negative on both sides. Diuresis is not frequent, painless. Pastosity of the feet and lower third of the legs. Varicose veins of the legs. When ECHO KG study revealed a slight expansion of the drug. Myocardial hypertrophy was not detected. LV contractility is reduced (PV - 50%). Hypo-akinesia of the posterior and posterior basal LV segments. Atherosclerosis of the aorta, sash AOK. Shutters MK sealed. MK and TK insufficiency. LV diastolic dysfunction - type 1 (Table 5).

Table 5
Indicators of ECHO KG and lipid spectrum of patient D. Indicators Hospital stage 3 months ECHO KG KDR LV (cm) 5.5 5.7 DAC LV (cm) 4.06 4.1 LP (cm) 4D 4.2 MZHP (cm) 1.06 1,1 WLW (cm) 1.06 1,1 PV (%) fifty 52 Lipid spectrum OXS (mmol / L) 5.9 5,6 TG (mmol / L) 2,5 2.2 LDL (mmol / L) 4.7 4.02 HDL (mmol / L) 0.8 1.01

In the hospital, therapy was prescribed: amlodipine 5 mg × 1 time per day, aspirin cardio 100 mg × 1 time per day, diuver 10 mg × 1 time per day, sylt 75 mg × 1 p / day, enalapril 5 mg × 2 times per day, concor 5 mg × 1 time per day, atorvastatin 40 mg at night.

In a hospital, physical training was not carried out in connection with the decompensation of hypertension. He was discharged from the hospital on the 11th day with positive dynamics in the form of stabilization of blood pressure within the target levels, improvement in general condition, relief of headache, dizziness, lack of signs of increased heart failure: decreased dyspnea during physical exertion, relief of edema of the lower extremities. 14 days after discharge from the hospital, the Treadmill test was performed as planned: TFN - 50 W, submaximal heart rate - 112 beats per minute.

After 3 months, when the treadmill test was repeated, a slightly positive dynamics was revealed in the form of a slight increase in TFN to 60 W and the absence of a statistically significant increase in submaximal heart rate from 112 beats. per minute up to 116 beats. per minute. When monitoring the dynamics of the lipid profile: the level of total cholesterol, the level of LDL, TG did not significantly change. According to ECHO KG, there was no significant improvement in intracardiac hemodynamics.

Thus, the appointment of the drug O-3 PUFA Omacor 60 minutes before the start of controlled physical training in the form of a dosage walk against the background of standard drug therapy in elderly patients with coronary heart disease with chronic heart failure, in the long term (6 months or more) after MI, increases tolerance to physical activity, provides positive changes in ECHO KG and blood lipid parameters and a decrease in the total number of adverse cardiovascular events, helps to reduce the progression of heart failure.

The proposed method was applied in 33 patients and can improve the rehabilitation of elderly patients with ischemic heart disease with chronic heart failure who have had MI due to the realization of antianginal, anti-ischemic and hemodynamic effects.

LIST OF USED LITERATURE

1) Piepoli M.F., Davos C, Francis D.P. et al. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) // BMJ. - 2004 .-- Vol.328. - P. 189.

2) Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur Heart J. - 2008. - No. 29. - 2388-2442.

3) Catherine De Maeyer, Paul Beckers, et al. Exercise Training in Chronic Heart Failure // Ther Adv Chronic Dis. - 2013 .-- 4 (3). - 105-117.

4) Cardiac rehabilitation: a practical guide. Ed. J. Niebauer. - Per. from English, ed. Yu.M. Pozdnyakova. - M .: Logosphere, 2012 .-- 328 s (p. 101).

5) Nikolaeva L.F., Aronov D.M. Exercise therapy for myocardial infarction and chronic coronary heart disease // Therapeutic physical culture / Ed. V.A. Epifanova. - 2nd ed. - M., 2002.

6) Perutsky D.N., Makeeva T.I., Konstantinov S.L. The basic concepts of post-infarction remodeling of the left ventricular myocardium. SCIENTIFIC NOTES. Series Medicine. Pharmacy. - 2011 .-- 10 (105). - Issue 14. - 51-59.

7) Moneyless A.V. The use of passive muscle training in comprehensive rehabilitation for myocardial infarction in elderly patients. Abstract of Cand. diss. - 2011 .-- 23 p.

8) Patent for invention No. RU 2329780 of 07.20.2006. Author (s): Bakhovudinova O.V., Zaitsev N.M., Avdonchenko T.S., Tarasov N.I., Gzogyan M.N. Patent holder (s): OJSC Sanatorium Prokopyevsky.

9) National recommendations of the OSCH, RKO and RNMOT for the diagnosis and treatment of heart failure (fourth revision). ISSN 1728-4651. Journal of Heart Failure. - Volume 14. - No. 7 (81). - 472 S.

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11) Green P., Lund L.H., Mancini D. Comparison of Peak Exercise Oxygen Consumption and the Heart Failure Survival Score for Predicting Prognosis in Women Versus Men. Am J Cardiol. 2007. - Vol. 99. - 399 - 403.

12) Macchia A, Levantesi G, Franzosi MG, et al., For the GISSI-Prevenzione Investigators. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. EurJ Heart Fail. - 2005. - Vol. 7. - 904-09.

13) Finzi, A. A. Effects of n-3 polyunsaturated fatty acids on malignant ventricular arrithmias in patients with chronic heart failure and implantable cardioverter-defibrillation: a Substady GISSI-HF / A. A Finzi, R. Latini, S. Barlera at al. Am. Heart J. - 2011 .-- Vol. 161. - P. 338-343.

14) Poole CD., Halcox J.P., Jenkins-Jones S., Carr E.S., Schifflers M.G., Ray K.K., Currie C.J. Omega-3 Fatty acids and mortality outcome in patients with and without type 2 diabetes after myocardial infarction: a retrospective, matched-cohort study. Clin Ther. - 2013 .-- Vol. 35 (1). - 40-51. doi: 10.1016 / j.clinthera.2012.11.00.00. Date of treatment 06.23.14

Claims (1)

A method for the rehabilitation of elderly patients with coronary heart disease with chronic heart failure who have had myocardial infarction, which consists in conducting physical training by dosed walking on the background of standard drug therapy with antiplatelet agents, β ₁ -adrenergic blockers, diuretics and ACE inhibitors, characterized in that when dosed walking through 6 or more months after myocardial infarction 60 minutes before the start of physical training, patients are prescribed an omega-3-sex drug unsaturated fatty acids (Omacor).