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79ЭФФЕКТИВНЫЕ МЕТОДЫ ЛЕЧЕНИЯ СТЕНОКАРДИИ
Арзикулов Абдурайим Шамшиевич Юсупов Кахрамон Мухитдинович Абдурахимов Абдухалим Холиддинович Нугманов Озодбек Журабойугли
Андижанский государственный медицинский институт
Стенокардия - частое проявление ишемической болезни сердца и часто является результатом проблем с коронарными артериями. Стенокардия (лат. Angina pectoris; лат. Боль в груди) - это боль, которая возникает в результате повреждения сердечной мышцы (миокарда) в периоды повышенной сердечной деятельности в результате нарушения кровотока и снижения поступления кислорода. Это очень опасное заболевание, которое широко распространено среди населения нашей планеты. В этой статье рассматриваются эффективные способы лечения этого заболевания.
Ключевые слова: стенокардия, ишемическая болезнь сердца, коронарная артерия, миокард.
STENOKARDIYANI DAVOLASHNING EFFEKTIV USULLARI
Stenokardiya yurak ishemik kasalligining keng tarqalgan ko'rinishi va ko'pincha koronar arteriya bilan bog'liq muammolar natijasi hisoblanadi. Stenokardiya (Angina pectoris; lotincha ko'krak qafasi og'rig'i) - qon oqimining buzilishi va kislorod bilan ta'minlanishning pasayishi natijasida yurak faoliyati kuchaygan paytlarda yurak muskuli (miokard) shikastlanishidan kelib chiqadigan og'riq. Bu sayyoramiz aholisida keng tarqalgan juda xavfli kasallik. Maqolada ushbu kasallikni davolashning effektiv usullari haqida muhokama qilinadi.
Kalit so'zlar: Stenokardiya, yurak ishemik kasalligi, koronar arteriya, miokard.
EFFECTIVE METHODS OF TREATMENT OF ANGINA PECTORIS
Angina pectoris is the most common manifestation of myocardial ischaemia and is often a consequence of coronary artery disease (CAD). Angina pectoris (Latin for chest pain) is pain that is caused by injury to the heart muscle (myocardium) during times of increased cardiac activity as a result of impaired blood flow and reduced oxygen supply. It is a common disease in the population of our planet. Complications are very dangerous.
This article discusses effective methods of treatment of this disease.
Keywords: Angina pectoris, myocardial ischaemia, coronary artery disease, myocardium.
DOI: 10.24411/2181-0443/2020-10101
Introduction: In recent years, the published global death cause and disease burden analysis report pointed out that the number of global coronary heart disease deaths exceeded 7 million, ranking first among 235 single-cause deaths. According to the 2017 global research reports, coronary heart disease (CHD) is the worldwide leading cause of disability and death, the morbidity. Angina Pectoris is a medical term for chest pain, which occurs due to an obstruction in the coronary artery. Angina is hard to differentiate from the other types of chest pain. It is not a disease in its own, but a symptom for many other life-threatening heart diseases. Angina pectoris is a sudden, sharp, intense and crushing pain
that radiates across the chest and spreads to the neck, jaw, shoulders, arms, and into the back. Angina pectoris is NOT a heart attack. As discussed below, angina pectoris is a sign of myocardial ischemia (injury to the heart muscle) and not a myocardial infarction (heart attack ~ death of heart muscle). This means you heart muscle is getting too little oxygen for its needs. However, angina pectoris often precedes a heart attack and can exist for months or years before a heart attack occurs. It should therefore be seen as a warning sign of an impending heart attack. The myocardium of the heart is constantly working and pumps blood throughout the body by contracting and relaxing. Being such an active part of the body, it needs a constant supply of oxygen and nutrients, which means a good blood supply.
As the activity increases, the heart has to work harder and faster. A slight restriction of the blood supply may not cause any symptoms or damage when at rest or with moderate activity. However, if there is increased activity like during exercise, then the heart needs an intact blood supply with sufficient oxygen availability. If this is not available then the heart muscle tissue undergoes damage known as ischemia. The muscle does not die but is injured. If this injury is severe or persistent, it may lead to death to a portion of the heart muscle which is known as an infarct (myocardial infarction or heart attack). Angina pectoris is most commonly due to progressive narrowing of the coronary artery so if left untreated the attacks will get worse and more frequent until a person has a heart attack. Since the arm, neck and heart develop from the same embryonic tissue, angina typically causes pain to radiate to the arm, particularly left arm, and the neck. It tends to last for a few minutes and subside with rest or the use of nitrates.
Drug therapy. Nitrates are prescribed to widen the blood vessel by improving the blood flow to the heart muscle. Anti-platelets, such as aspirin reduce the blood clot and improve the blood flow, thereby reducing the risk of a heart attack. Beta-blockers block the action of certain hormones and manage abnormal heartbeat. Thus, it makes the heart to beat slowly with less force and prevents angina. Statin blocks the action of certain enzymes that make the cholesterol. Thus, it reduces the cholesterol levels and helps in treating angina.
According to a group of scientists [1]: Angina pectoris, or symptomatic myocardial ischaemia, reflects an impairment of coronary blood flow, and usually a deficiency of available myocardial energetics. Treatment options vary with the precise cause, which may vary with regards to the roles of increased myocardial oxygen demand versus reduced supply. Traditionally, organic nitrates, p-adrenoceptor antagonists, and non-dihydropyridine calcium antagonists were the only commonly used prophylactic anti-anginal agents (Table 1).
Long-acting
B-adrenoceptor antagonists
d i h y d ro py ri d i ne
antagonists
NTG patches
ISMN
ISDN
Extent of exercise
prolongation (%)
Headaches Development of tolerance Rebound angina
Worsening of asthma Worsening of claudication Lethargy
Constipation Ankle swelling (mainly Diltiazem)
Table 1: Comparison of "standard" prophylactic anti-anginal agents for management of exertional angina. Abbreviations: NTG = nitroglycerine; ISMN = isosorbide mononitrate; ISDN = isosorbide dinitrate.
The treatment for angina pectoris is based on the extent of damage caused to the heart. In case of mild angina medications, some lifestyle modifications are helpful to reduce the symptoms and improve the blood flow.
Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE-inhibitors in most cases. Antianginal medication consists of ^-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin-receptor antagonists represent potential drugs that may prove useful in these patients in the future [2]. Pharmacotherapy in patients with CMD is challenging as there are currently no large randomized studies available. Nevertheless, various substances have been studied for the treatment of CMD. In 2013, the guideline on the management of stable CAD by the European Society of Cardiology has addressed the issue of CMD and recommended the use of aspirin, statins, ^-blockers and calcium channel blockers [3]. The results of the research showed that [4, 5] the standard approach regarding pharmacotherapy consists of an ACE-inhibitor and a statin as both drugs have shown to improve coronary microvascular dysfunction in small randomized studies. ACE-inhibitors can improve coronary microvascular function as assessed by coronary flow reserve. In one randomized, placebo controlled study, patients with CMD and impaired coronary flow reserve received a 16 week treatment with quinapril or placebo [6]. The treatment group showed a significant improvement of CFR which was linked to reduced angina frequency. Statins can reduce LDL-levels and thereby cardiovascular risk. Moreover, due to their pleiotropic effects a reduction of vascular inflammation and an improvement of endothelial function may occur. Small randomized studies have shown beneficial effects in terms of prolongation of exercise duration in CMD patients taking pravastatin, fluvastatin or simvastatin compared to placebo [7-9]. Based on these studies the use of statins and ACE-inhibitors is recommended for most patients with CMD unless severe side effects or contraindications are present. Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors. Antianginal medication consists of ^-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individualized titrated combinations of these drugs up to 30 % of patients have refractory angina.
According to a group of scientists [10] coronary heart disease angina pectoris is a common and frequently occurring disease in internal medicine, which has caused great harm to the lives and health of the people.[11] In recent years, the published global death cause and disease burden analysis report pointed out that the number of global coronary heart disease deaths exceeded 7 million, ranking first among 235 single-cause deaths.[12]The results of the study show that coronary heart disease is the second leading cause of death in the Chinese population. Standardized drug interventions and revascularization treatments can achieve certain effects. However, how to further improve the clinical efficacy, reduce the incidence of cardiovascular events, improve the clinical symptoms of patients, and improve the quality of life of patients, these problems are the key issues to be resolved in the treatment of coronary heart disease angina.[13,14] Chinese medicine treatment of coronary heart disease angina, in addition to oral medication, there is acupuncture therapy. With the increasing side effects of drug use and drug resistance,
acupuncture is becoming more and more popular.[15] Acupuncture can significantly improve the vascular endothelial function and cardiac function in the animal model of myocardial ischemia in coronary heart disease, and effectively improve the blood lipid level and the expression of related proteins and inflammatory factors in coronary heart disease model animals, thus effectively delaying the progression of atherosclerosis.[16] Evidence from basic animal studies supports the efficacy of acupuncture in the treatment of coronary heart disease with angina pectoris, and several clinical randomized controlled trials support this theory. Compared with conventional treatment, acupuncture can reduce the symptoms of angina pectoris in patients with coronary heart disease, improve electrocardiogram, reduce the amount of nitroglycerin, and improve hemodynamics [17].
Another group of Chinese scientists is of the opinion that [18]: Angina pectoris (AP) is a clinical syndrome characterized by paroxysmal and squeezing pain, which caused by acute myocardial ischemia and hypoxia [19]. According to the 2017 global research reports, coronary heart disease (CHD) is the worldwide leading cause of disability and death, the morbidity and mortality of CHD in China is also rising year after year [20]. Thus, AP caused by stable, unstable CHD and myocardial infarction after percutaneous coronary stent implantation is a very common phenomenon, which has great impact on physical and mental health. Nowadays the enormous progress had made in the comprehensive treatment of AP. However, as the most widely used specific drugs for the treatment of AP in modern medicine, nitrates have shown great efficacy but also with the disadvantages of easy drug resistance, drug inefficiency, adverse reactions such as headache, facial flushing, rapid heart rate reflex, hypotension and so on [21].
Inspired by the ancient book "Ancient and Modern Medical Mirror", KA is processed by combining modern pharmacology and pharmaceutical technology. The TCM and specific modern pharmacological effects that how they impact and work in the drug on patients can be seen in Table (Table 2). In recent years, more and more clinical research about KA on the treatment of AP were carried out, which indeed shown obvious effect of relieving AP by resisting myocardial ischemia and coronary spasm and improving the tolerance of myocardial cells to hypoxia [22]. KA is expected to be an alternative or combination of nitrate drugs for the short-term treatment of acute AP. However, there is still a lack of the related system evaluation and meta-analysis to provide further clinical evidence. Thus, this study set strict inclusion and exclusion criteria, focused on the effectiveness and safety of KA in the treatment of AP, and summarized all the results of included RCTs, so as to provide some reference for subsequent clinical treatment.
Ingredient TCM effects Pharmacological effects
Sandalwood oil Regulate Qi to disperse stagnation, open the heart tips Resist oxidation, expand coronary
Piper longum oil Relieve pain
Asarum Regulate Qi and disperse cold to dredge channels and collaterals Resist myocardial ischemia, resist inflammation, relieve pain
Galangal
Borneol Relieve pain Resist thrombosis, resist inflammation, regulate endothelial function
Table 2. The TCM and Pharmacological effects of each ingredient in KA.
According to these researchers [18], the results of this systematic study and analysis support the clinical use of KA for the treatment of coronary heart disease AP. However, due to the limitations in the quantity and quality of the included literatures, more large-scale and high-quality RCTs with well design are needed, and more attention should be paid to the comparative observation of patients' long-term follow-up and the internal biochemical changes.
Due to the ageing of the population, and increased survival from coronary artery disease, the number of patients with RA is expected to rise exponentially. Despite the developments of novel technologies for the treatment of RA, none of them found wide clinical application (to date). Microvascular dysfunction, alone or in combination with epicardial coronary disease, is thought to contribute significantly to refractory angina. However, most of the techniques developed to improve RA symptoms have not been tested specifically on patients with microvascular dysfunction [23]. The utility of several new therapeutic tools have been tested in the management of RA in the last three decades, however, only a small portion of these were validated specifically on the population of patients with RMVA. Namely, EECP has been shown to improve coronary flow reserve (a marker of microvascular function) [24], index of microvascular resistance [25] along with improvements in CCS angina class and exercise tolerance [26-27]. These effects were thought to be mediated by stimulating new collateral artery formation and improved endothelial function. CSR implantation in eight patients with MVD in RA patients were associated with symptom improvement, increased exercise tolerance and quality of life, and myocardial perfusion reserve index on dipyridamole stress cardiac magnetic resonance, showing therapeutic potential in this challenging subgroup of patients. Cell therapy is another promising option to address refractory microvascular angina. Bone marrow-derived progenitor cells have been demonstrated to promote neovascularization and consequently myocardial perfusion leading to increased contractility in in vivo models [28].
Stem cell teraphy. Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic option for RA patients. Different BM autologous vasculogenic cell populations, including unfractioned mononuclear cells, CD34+ or CD133+ cells, have been injected into ischemic areas to ameliorate perfusion of LV territories not otherwise amenable to revascularization [29]. There are two most common delivery routes of these cells: Intra-myocardial and intra-coronary. Circulating levels of CD34+ cells predict advanced CAD, physical function, adverse clinical outcomes after myocardial infarction, and overall survival [30,31]. In preclinical myocardial infarction models, isolated CD34+ cells were associated with improvements in overall myocardial performance and regional wall motion, and they showed potential in reducing fibrosis and increasing angiogenesis [32]. Safety and feasibility of intramyocardial injection of autologous CD34+ stem cells were demonstrated in a Phase I/IIa double-blind, randomized controlled trial on 24 RA patients, showing potential bioactivity with improvement in CCS angina class. A phase II randomized trial, including 167 RA patients, showed a significant improvement in both angina symptoms and exercised tolerance with intramyocardial injection of autologous CD34+ stem cells over placebo at 6, 12 months [33] with persistent results at 24 months follow-up [34]. In addition, there was a trend towards a reduction in the rates of major adverse cardiac events (p = 0.08) [35]. Based on these promising results, a phase III randomized (RENEW, efficacy and safety of targeted intramyocardial delivery of auto CD34+ stem cells for improving exercise capacity in subjects with refractory angina) trial was launched. However, the trial was terminated prematurely by the sponsor, due to financial reasons, recruiting only 112 patients of planned 444, which was not sufficient to test its efficacy end-point. Pooled analysis of the three previous trials, including a total of 276 patients demonstrated sustainable improvements in exercise capacity, angina frequency and
mortality at 3, 6, and 12 month-time points. The safety and efficacy of intracoronary injection of autologous CD34+ stem cells in two concentrations (low-dose and high-dose) were evaluated in 38 patients with no option CAD and left ventricular dysfunction in a phase I randomized trial [36]. The main findings of the trial were improved angina, left ventricular ejection fraction, reduced remodeling at one and five years follow-up [37,38]. Intriguingly, improved clinical outcomes and heart function were correlated with angiogenesis assessed by coronary angiography, rather than CD34+ dose. Trans-endocardial delivery of another autologous bone marrow-derived cells, CD133+ cells, were proved to be safe and feasible in two small phase I randomized trials not powered for efficacy end-points [39,40]. Another recent phase I randomized trial of intramyocardial injection of CD133+ cells in RA patient subset with LV dysfunction (LV < 45%) confirmed the safety profile of the previous two trials and showed significant improvements in CCS angina class, myocardial perfusion and function assessed by single-photon emission computer tomography at 12 months [41]. Moreover, improvements in myocardial perfusion were positively correlated with the proangiogenic growth factors, hepatocyte growth factor and platelet-derived growth factor type bb, substances involved in neovascularization, endothelial and muscle cell growth [42,43]. The most recent and the largest (8 RCTs, 526 patients) meta-analysis to date concluded that cell-based therapies improve not only indices of angina (angina episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications), but also mortality and major adverse cardiovascular events [44]. Despite recent advancements in this field, questions regarding optimal cell type, dosage, delivery method duration of efficacy remain open. Thus, larger Phase III studies are needed to address these issues, assessing both clinically relevant outcomes (quality of life, cost-effectiveness and MACE) and quantitative assessment of myocardial perfusion (PET and cardiovascular magnetic imaging).
Conclusion: This article discussed ways to treat angina pectoris. Detailed information was provided on effective drugs and stem cell therapy in the treatment of this ischemic disease, which is considered actual and dangerous. We hope that new and other effective methods of treatment will be developed.
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