The Influence of Prior Therapy on the Course of Myocardial Infarction and the Effectiveness of Systemic Thrombolysis

The dissertation is devoted to the study of the influence of prior pharmacotherapy, including antiplatelet agents, angiotensin-converting enzyme inhibitors, and β-adrenoblockers, on the course of myocardial infarction, the effectiveness of systemic thrombolysis, dynamic blood viscosity, and heart rate variability in patients during the acute and subacute periods of the disease. The work is based on clinical observation of patients who had received therapy before the development of myocardial infarction and is aimed at assessing the depth of myocardial necrosis, the character of complications, the need for thrombolytic therapy, and the state of autonomic regulation of cardiac activity.

The practical significance of the work is related to the analysis of real clinical practice, in which intake of the listed agents does not always prevent the development of myocardial infarction but contributes to a reduction in the necrosis zone and the proportion of life-threatening complications. The results have been implemented in the therapeutic work of a city clinical hospital and in the educational process of a medical academy.

A major achievement of modern cardiology is the development of pharmacological agents capable of influencing the outcomes of cardiovascular diseases (CVD) - reducing the probability of death and severe complications - and thereby prolonging the patient's life. The action of these agents has been proven through large randomized controlled trials conducted under strict protocols that imply careful monitoring of drug intake, effectiveness, and safety. Therefore, to achieve similar results in clinical practice, it is necessary at minimum to prescribe the drugs in the same doses and to ensure the same patient adherence to therapy as in the trials conducted [16].

However, in practice, patients do not always receive therapy corresponding to current evidence-based medicine guidelines. In Russia, according to data obtained at the State Research Center for Preventive Medicine, approximately 40% of the population suffer from hypertensive disease (HD), while 30-40% of them are unaware of their disease, and only one-tenth control their arterial pressure (AP). According to the national pharmacoepidemiological study PYTHAGOR II, a survey of 3,789 patients with HD in 85 cities of Russia established that only 6.1% of patients receive continuous long-term antihypertensive therapy, while 31.5% take antihypertensive drugs only when feeling unwell and experiencing elevated AP [50]. The most frequently prescribed agents for HD are angiotensin-converting enzyme inhibitors (ACEI): 40% of patients receive these drugs as monotherapy. β-adrenoblockers (β-AB) account for 18.6% of the overall structure of antihypertensive agents used [27]. Combined therapy accounts for only 3.4%, although it is relevant even for patients with grade 1 and 2 HD, who constitute 80% of all patients with elevated AP [50].

In 2001 in Russia, under the auspices of the All-Russian Scientific Society of Cardiologists and within the framework of the international pharmacoepidemiological study ATP survey (Angina Treatment Pattern), an assessment of the quality of treatment of patients with stable angina was carried out [44]. The data obtained indicate that, overall, in the treatment of chronic ischemic heart disease (IHD), combined antianginal therapy predominates, prescribed to 76% of patients, with 43.4% of patients receiving a combination of nitrates with β-AB, and 15.9% receiving a combination of three drug groups: nitrates, β-AB, and calcium antagonists. Antiplatelet agents are used by 89.8% of patients. Lipid-lowering agents are insufficiently used in our country - only 17.1% of angina patients take statins. Analysis of the daily doses of the most frequently used antianginal agents shows that a significant number of Russian patients take medications in minimal doses, while the number of patients using agents in effective doses is insufficient.

The few existing studies (HDFP, ATLAS), which compared therapy prescribed in accordance with evidence-based results with therapy close to real clinical practice, showed how deviation from evidence-based medicine recommendations worsens the final treatment outcome [124, 140]. In this case, the risk of complications, including myocardial infarction (MI), is significantly increased in patients with a history of HD and IHD. At the same time, the question of the influence of prior therapy on the character, course, and effectiveness of subsequent treatment of developing MI in these patients remains insufficiently studied.

The literature contains relatively few works devoted to this question, and they mainly concern prior aspirin intake and lipid-lowering agents [76, 126, 144, 171].

It should be noted that the action of the pharmacological agents used is based not only on changes in hemodynamic parameters but also on influence on the state of microcirculation, blood rheology, the coagulation system, as well as vascular tone, dysfunction of which is one of the main causes of initiation of the atherosclerotic process and its further progression [15, 57, 114, 128]. Given the major role of these mechanisms in atherogenesis, spasm, and thrombosis of coronary arteries, it may be assumed that the intake of pharmacological agents can influence the course and character of MI, as well as the effectiveness and possible side effects of MI treatment, in particular, thrombolytic therapy.

While the influence of ACEI and β-AB on the autonomic nervous system is recognized, the effect of their prior intake on heart rate variability (HRV) in the acute and subacute periods of MI has not been established.

In the literature we studied, we did not find clear and unambiguous answers to these questions, which determined the aim of the work.

Aim of the study: to investigate the influence of prior therapy with antiplatelet agents, ACEI, and β-AB on the course of MI, the effectiveness of systemic thrombolysis in MI, as well as on indicators of dynamic blood viscosity and HRV in the acute and subacute periods of MI.

Objectives of the study:

1. To determine the influence of prior intake of antiplatelet agents, ACEI, and β-AB on the depth of myocardial damage during infarction, the course of MI, and the character of complications.

2. To evaluate the influence of prior therapy on the effectiveness of systemic thrombolysis.

3. To determine the influence of prior pharmacotherapy on indicators of dynamic blood viscosity in the acute period of MI.

4. To establish the effect of prior therapy on HRV indicators in the acute and subacute periods of MI.

Scientific novelty: new data have been obtained on the influence of prior pharmacotherapy on the course of MI and the character of complications; the degree of effectiveness and safety of thrombolytic therapy in patients receiving prior therapy has been established; the influence of pharmacotherapy used in real conditions on the initial state of the myocardium and the lipid profile has been noted; the influence of prior therapy on dynamic blood viscosity in the acute period of MI has been established, and a pattern between blood viscosity level and adrenergic activity has been revealed; the influence of ACEI and β-AB on the level of sympathetic and parasympathetic activity in the acute and subacute periods of MI in patients receiving them has been examined.

Practical significance

Analysis of the real situation established that intake of ACEI, β-AB, and antiplatelet agents does not always prevent the development of MI, which dictates the need to develop a system for monitoring the intake of these agents.

During follow-up of the course of MI, it was noted that, although prior drug intake does not reduce the number of complications, it significantly reduces the proportion of life-threatening ones, which apparently is associated with a smaller necrosis zone in these patients.

Prior therapy reduces the need for systemic thrombolysis without affecting its side effects.

Statements for defense

1. Prior pharmacotherapy, represented mainly by ACEI, β-AB, and antiplatelet agents, exerts a protective effect on the myocardium during infarction in patients receiving it, manifesting as a smaller depth of necrosis determined by the presence of Q wave on the electrocardiogram (ECG).

2. By exerting a positive influence on endothelial function, atherogenesis, and thrombogenesis, prior intake of these agents prevents complete thrombotic occlusion of the coronary vessel, thereby reducing the need for thrombolytic agents for revascularization. The effectiveness and side effects of systemic thrombolysis do not depend on the presence or absence of prior pharmacotherapy.

3. The course of the acute and subacute periods of MI depends to a greater extent on the existing aggravated (cardiovascular) history than on the presence of prior therapy.

4. Prior therapy exerts a positive influence on indicators of dynamic blood viscosity in the acute period of MI, allowing it to be maintained at lower values. Elevated blood viscosity is associated with increased adrenergic activity. Prior intake of ACEI and β-AB reduces sympathetic activity in the acute and subacute periods of MI while maintaining the activity of the parasympathetic nervous system.

Implementation of research results

The results of the study have been implemented in the work of the Municipal Healthcare Institution "City Clinical Hospital No. 5" of Nizhny Novgorod and in the educational process of the Department of Faculty and Polyclinic Therapy of the Nizhny Novgorod State Medical Academy.

Approval of the work

The materials of the dissertation were presented at the Regional Scientific and Practical Conference (Dzerzhinsk, 2006), at a meeting of the Nizhny Novgorod Regional Organization of Therapists on 31.10.2005, and at a joint extended meeting of the Department of Faculty and Polyclinic Therapy and the Department of Therapy of the Faculty of Advanced Training of Physicians of the Nizhny Novgorod State Medical Academy with the participation of the problem commission (Nizhny Novgorod, 2006).

Publications. On the topic of the dissertation, 6 scientific works have been published.

Scope and structure of the work

The dissertation consists of an introduction, a literature review, a chapter on materials and methods of investigation, 4 chapters presenting the results of original research, discussion of results, conclusions, practical recommendations, and a list of references comprising 177 sources. The work is presented on 137 pages of typewritten text and is illustrated with 35 tables and 29 figures.