For whom is aspirin dangerous? New facts about the famous medicine

“The history of the use of acetylsalicylic acid dates back thousands of years,” says Candidate of Medical Sciences, researcher at the Scientific Center for Neurology Anton Raskurazhev . “Even in ancient Egyptian papyri dating back to the 16th century BC. e., among the descriptions of herbal preparations, the plant salix is ​​mentioned, today known as willow. The Ebers Papyrus, one of the oldest medical texts, talks about the use of a decoction of willow tree bark as a pain reliever. From Hippocrates' we know that he prescribed willow bark extract to patients as an antipyretic and analgesic.

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The results of the first clinical study on the use of willow bark as a treatment for patients with malaria were published in 1758 in England. In 1763, the active substance of this drug - salicylic acid - was described, in 1828 the active substance called “salicin” was identified, and in 1859 the industrial production of salicylic acid was established.

In the 19th century These drugs were successfully used to treat rheumatism and rheumatic fever, which were common at that time. Then doctors first noticed the side effects of this medicine: first of all, on the gastrointestinal tract.

There is a legend that says that it was thanks to aspirin that Grigory Rasputin of Emperor Nicholas II and gained influence over the imperial family He canceled the newfangled aspirin to Tsarevich Alexei

In the 20th century, aspirin gained fame as a powerful and versatile anti-inflammatory and antipyretic drug, and this drug became the best-selling drug among over-the-counter drugs. And after the antiplatelet effect (suppression of blood clotting) of acetylsalicylic acid was discovered, doctors began to recommend daily aspirin to prevent stroke and prevent cardiovascular diseases.”

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Aspirin: benefit or harm

Surgical department No. 2 (city center for gastroduodenal bleeding of ulcerative etiology), surgeon Konkin D.K.

Aspirin (acetylsalicylic acid) is one of the most famous and common medicines. About 80 billion aspirin tablets are consumed worldwide every year.

It all started when, on June 23, 1971, British pharmacologist John Vane published his research on the mechanism of action of acetylsalicylic acid in the article “Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs,” aspirin began to be used throughout the world for the prevention of cardiovascular diseases. Wayne found that acetylsalicylic acid slows down the production of prostaglandins and thromboxane A2 in platelets, which determines its antithrombotic and cardioprotective effect, which was subsequently convincingly proven in many large studies and meta-analyses.

It has become obvious that long-term use of this drug in low doses can be used to reduce the risk of thrombosis, including in the coronary and cerebral arteries, which significantly reduces the risk of developing heart attacks, ischemic strokes and other cardiovascular problems. In 1982, Vane was awarded the Nobel Prize for this revolutionary discovery, and Queen Elizabeth II of Great Britain knighted him. Very quickly, the antiplatelet (“blood-thinning”) effect of the drug overshadowed its anti-inflammatory properties, and at present, the prevention of thrombosis is the only practically justified use of this drug.

By “thinning” the blood, aspirin not only prevents blood clots, but also increases bleeding, which makes its use as an antipyretic dangerous in the case of many infectious diseases (flu, Dengue fever, etc.). Children should not be given aspirin during viral fevers due to the risk of developing the rare but deadly Reye's syndrome. For these reasons, other nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are now preferred to reduce body temperature and control pain and swelling.

Once you reach a certain age or if you have individual risk factors, your doctor may recommend taking daily aspirin in low (50-100 mg) but effective doses to prevent myocardial infarction and other diseases associated with blood clots. Even first aid for myocardial infarction includes chewing one aspirin tablet, which significantly increases the patient’s chances of a favorable outcome.

However, where there is good, there is also evil. A well-known unpleasant side effect of NSAIDs is the induction of ulceration and bleeding in the upper gastrointestinal tract. Alas, even the lowest cardioprotective doses of aspirin increase the risk of bleeding from the upper gastrointestinal tract by 2-3 times - one of the most dangerous complications of peptic ulcer disease.

Now that in developed countries doctors have learned to effectively deal with the main cause of ulcers, the bacterium Helicobacter pylori, and are systematically achieving successful eradication of this microorganism, the main cause of complications of peptic ulcer disease and its recurrence is the widespread use of non-steroidal anti-inflammatory drugs, including low doses of aspirin for prevention cardiovascular diseases.

However, at this point great confusion begins in the minds of the masses. And popular misconceptions have always created fertile ground for unscrupulous extortion of money from patients. So in the case of aspirin, pharmaceutical companies decided to strongly support the myth that stomach ulcers are formed as a result of “burning” the mucous membrane with acetylsalicylic acid, that is, aspirin. The media, with the support of the same pharmaceutical companies, began to broadcast about new medicines that also contain acetylsalicylic acid as an active ingredient, but are less dangerous in terms of the development of complications from the stomach and intestines (Cardiomagnyl, Aspirin Cardio, etc.).

The effect is achieved by adding an enteric coating and magnesium salts, which, according to manufacturers, ensure that the drug passes through the stomach unchanged and begins to be absorbed only in the duodenum. Thus, people began to be told that an aspirin tablet coated with a special coating can completely protect the stomach from the negative effects of acetylsalicylic acid during long-term use. However, in the 1990s, a number of large studies showed that replacing regular aspirin with a cardiac coated aspirin does not provide any particular advantages, since aspirin has its main effect on the body after it enters the blood, and it does not matter where exactly this happens - in stomach, or intestines. It does not have any local irritant effects, and the risk of stomach ulcers is the same when taking any form of the drug. In fact, it doesn’t really matter in what form you take anti-inflammatory drugs - orally, as an injection or as an ointment: the side effects on the stomach are the same.

In order to protect the patient from the development of symptomatic drug-induced gastric and duodenal ulcers, a number of measures have been developed, ranging from early preventive diagnosis and screening examination to preventive drug treatment. According to the manufacturer's instructions, in order to reduce the irritating effect on the stomach, it is recommended to drink aspirin with a weak solution of baking soda or alkaline mineral waters. According to some doctors, you can add a glass of milk or 1-2 tablespoons of cottage cheese to the list. These measures reduce acid production in the stomach in response to the inhibition of certain enzymes responsible for the formation of gastric wall protectors (prostaglandins). It is more rational to take the drug taken after a meal in the first half of the day (not at night) with a sufficient amount of water, at least a glass. For patients taking aspirin-type drugs for a long time, for timely detection of complications, it is necessary to undergo an annual endoscopic examination of the stomach and duodenum, a general blood test and stool test for occult blood. Sometimes the simultaneous use of aspirin and drugs that protect the stomach wall (omeprazole, pantoprazole, etc.) is justified.

Insidious pills

As the media wrote, scientists did not find evidence of a decrease in the number of heart attacks and strokes in those taking the medicine, but statistically determined that their risk of internal bleeding increased. “RG-Week” figured out what kind of research we are talking about, and whether the situation with an old and seemingly well-studied drug is really so serious.

The publications raised understandable concerns among many: firstly, aspirin is one of the most commonly prescribed medications used to reduce relapses of cardiovascular diseases, including in older people. Secondly, this is an over-the-counter medicine that can be freely purchased at pharmacies, and many people perceive it as an absolutely safe remedy for many ailments - we drink it for headaches, colds, and some even with a hangover.

As for the effect of acetylsalicylic acid on blood vessels, this drug reduces platelet aggregation (in other words, their ability to “stick together”, forming blood clots). Consequently, its use reduces the risk of blockage of blood vessels and disruption of the heart, brain, and other organs.

But there is also a flip side to the coin: the medicine increases the risk of bleeding, including in the gastrointestinal tract. Which, by the way, is stated in the instructions for its use.

An article with the results of the international ASPREE study, which was conducted by a group of scientists from Australia and the USA, was published in the September issue of The New England Journal of Medicine. Its short translation from English into Russian is what caused so much noise. The results of this study were also discussed at the recent European Congress of Cardiology. The work is representative: scientists summarized data on 19 thousand patients, whose average age was 74 years, and monitored them for about five years.

Half of the participants took a small dose of aspirin, the rest (control group) took a placebo. During observation, the incidence of cardiovascular diseases, including vascular accidents, was the same in both groups. But complications in the form of bleeding in the group that took the medicine were almost 1.5 times higher (361 and 265 cases, respectively, for a group of 9.5 thousand people).

So, does this mean that aspirin is still dangerous? “RG - Week” addressed this question to cardiologist Igor Zhirov.

Competently

Igor Zhirov, Professor of the Department of Cardiology of the Russian Medical Academy of Continuing Professional Education, Leading Researcher at the National Medical Research Center for Cardiology

— I can immediately say that the information “aspirin kills” is not true. Cardiologists are, of course, aware of this research. We did not see anything completely new that we did not know before in its results. Journalists, citing the ASPREE study in publications, did not pay attention to an essential detail: this study did not study cardiovascular mortality. The purpose of the study was different - to evaluate, among other things, the possibility of using aspirin for the prevention of Alzheimer's disease (senile dementia) in elderly patients. It turned out that adding aspirin to therapy for these patients did not reduce the risk of dementia. In other words, taking aspirin as a prophylactic against senile dementia is useless.

As for the conclusion about an increase in the number of bleedings, there are no discoveries here; this is a known risk, and any cardiologist should take it into account. It should be said that any drug that we prescribe and prescribe can cause side effects. And this statement fully applies to aspirin. This is not a “harmless” remedy at all. If we start giving aspirin to everyone, regardless of age, regardless of what concomitant diseases the patient has, then such indiscriminate prescription of the drug may do more harm than good.

But if we prescribe aspirin to patients with coronary heart disease, those who have suffered a myocardial infarction, patients with atherosclerosis of the peripheral arteries of the lower extremities (intermittent claudication) - in all these cases the benefit of the drug is beyond doubt.

Now the approach to the appointment is as follows. We must carefully weigh all the risks for a particular patient. See if he has a stomach ulcer or other diseases of the internal organs. Place on one scale

risk factors for cardiovascular disaster, on the other - the risk of complications of other diseases. And evaluate. And the decision must be individual for each patient.

As for the “home” use of aspirin - treating a cold or relieving a hangover, here aspirin is taken in a short course, a day or two. And in these cases, the risk of complications from the gastrointestinal tract is minimal. But when there is a need for long-term use of the drug, there really are risks, and the doctor must take them into account when prescribing.

New data on the role of acetylsalicylic acid in the treatment of COVID-19

On June 15, during “Scientific Tuesday,” the head of the department of fundamental and clinical problems of thrombosis in non-infectious diseases of the Federal State Budgetary Institution “National Medical Research Center for Traumatology and Medicine” of the Ministry of Health of Russia, Doctor of Medical Sciences. Igor Semenovich Yavelov presented data from randomized clinical trials on the use of acetylsalicylic acid in the drug therapy of COVID -19.

It has been proven that thrombus formation processes play a significant role in the progression of the new coronavirus infection. Currently, subcutaneous or intravenous administration of heparin drugs is widely used in the hospital for the treatment of COVID-19. However, evidence is accumulating that drugs that reduce the functional activity of platelets (antiplatelet agents) may also be useful, among which acetylsalicylic acid is most often used.

Thus, according to a pooled analysis of 6 retrospective studies, which included a total of 13,993 patients with COVID-19, the use of a low dose of acetylsalicylic acid prehospital or in the hospital indicated a twofold reduction in the risk of death when compared with those who did not receive this antiplatelet agent, regardless of the presence of other factors, associated with an unfavorable outcome of the disease. The results of the analysis of cases of initiation of acetylsalicylic acid use in a hospital were similar. At the same time, on the one hand, such a pronounced positive effect looks implausible, on the other hand, it is known that evidence of this kind can be misleading, since the decision to prescribe or not prescribe a drug to a particular patient depends on the decision of the doctor, whose motives are not always known , and there is never any certainty that the comparison groups were similar (comparable) in all features that could influence the outcome of treatment. Only randomized clinical trials can give a definite answer to the appropriateness of a particular approach to treating patients.

The results of the first of them were disappointing: in the multicenter open clinical trial RECOVERY, the administration of acetylsalicylic acid at a dose of 150 mg 1 time per day before discharge in patients hospitalized with COVID-19 had no effect on mortality over 28 days of observation compared with standard treatment of the disease. without the use of acetylsalicylic acid. However, there was no benefit when starting treatment within the first 7 days and later from the onset of symptoms, in the absence of the need for respiratory support/oxygen breathing and various forms of respiratory support, with or without the use of corticosteroids. There were no differences between groups in the frequency of patients requiring non-invasive and invasive pulmonary ventilation or renal replacement therapy. In general, the study began in the first days after hospitalization, and initially the severity of the disease was not critical (mechanical artificial ventilation was performed in only 5% of patients).

As a result, there is no reason yet to use acetylsalicylic acid in all patients hospitalized with COVID-19. Its study in this disease (including outpatient treatment) continues in a number of randomized clinical trials. Accordingly, it is possible that after new facts emerge, ideas about the role of acetylsalicylic acid in COVID-19 will be clarified or revised.

A spoon of tar

However, later doctors, without questioning the positive effect of aspirin for patients with cardiovascular diseases, began to say that its use for preventive purposes could do more harm than good to healthy people. It turned out that daily intake of aspirin leads to serious life-threatening diseases (stomach ulcers, bleeding, perforation of the mucous membrane of the small and large intestines, acute colitis, chronic intestinal diseases).

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75 mg for the core. Who “buries” aspirin and why?

“When the Scientific Center for Neurology examined the state of the blood while taking aspirin, it turned out that the drug reduces blood viscosity only in 50% of patients, in 30% it has no effect, and in 20%, on the contrary, it increases blood viscosity, thereby increasing the risk of stroke “said Marine Tanashyan, Doctor of Medical Sciences, Professor, Deputy Director for Scientific and Medical Work of the Scientific Center for Neurology of the Russian Academy of Medical Sciences.

Cardiologists also changed their recommendations. Now they also do not welcome the uncontrolled use of aspirin for preventive purposes. The drug is now prescribed only for signs of atherosclerosis and in the presence of laboratory confirmed increased blood clotting.

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ASPIRIN. Stable positions and new opportunities after the 100th anniversary

Antiplatelet drugs, in the absence of contraindications, are an essential component in the treatment and prevention of atherothrombosis. The International Committee for the Analysis of Trials of Antithrombotic Drugs regularly (as large studies are completed) organizes meta-analyses, the results of which have confirmed the effectiveness of aspirin in the treatment of patients with myocardial infarction (MI), acute coronary syndrome (ACS) without ST-segment elevation on the ECG in relation to reducing the risk of developing death and MI. In addition, the effectiveness of long-term use of aspirin in patients who have suffered ACS has been proven in relation to total death, MI and stroke. All this gave reason to include aspirin in the list of mandatory medications for the above pathology and was reflected in practical recommendations for doctors.

Despite the abundance of studies on antiplatelet drugs, until recently there was no clear answer to a number of questions: in particular, about the advisability of using antiplatelet drugs in patients with acute ischemic stroke, in the presence of a permanent form of atrial fibrillation, stable angina, and atherosclerotic lesions of the arteries of the lower extremities. In addition, the issue of the minimum effective dose of aspirin and the advisability of combinations of several antiplatelet agents and antiplatelet agents with anticoagulants has not yet been clarified. These, as well as other problems less covered in the domestic literature, will be the subject of this review.

In 2002, the results of another large meta-analysis were published [1] assessing the effectiveness of antiplatelet drugs, which included 287 studies (195 controlled in more than 135 thousand high-risk patients). The effectiveness of treatment with various antiplatelet agents was compared in 77 thousand patients. The results of the meta-analysis found that the use of antiplatelet drugs reduces the total risk of vascular events by 22%, non-fatal myocardial infarction by 34%, non-fatal stroke by 25%, and vascular death by 15%.

Aspirin remains the most widely used antiplatelet drug today, the clinical efficacy and safety of which has been confirmed by numerous controlled studies and meta-analyses. The mechanism of action of aspirin is associated with irreversible inhibition of platelet cyclooxygenase-1, which results in a decrease in the formation of thromboxane A2, one of the main inducers of aggregation, as well as a powerful vasoconstrictor released from platelets upon their activation. A pooled analysis of the results of 65 studies, which included 59,395 patients at high risk of developing vascular complications, showed that taking aspirin reduced the total risk of MI, stroke, and vascular death by 23% [1]. Prescription of low doses of aspirin (75-150 mg/day) for long-term therapy was no less effective than medium (160-325 mg/day) or high (500-1500 mg/day). In clinical situations, such as unstable angina, myocardial infarction and ischemic stroke, the initial dose should be at least 150 mg/day [1]. To date, few studies have been conducted using very low doses of aspirin (less than 75 mg/day), so the question of the effectiveness of a dose of the drug <75 mg/day remains open.

Aspirin in the treatment and prevention of ischemic stroke

Aspirin in doses from 30 to 1500 mg/day has been used for a long time and has been successfully used in the secondary prevention of ischemic stroke. Direct comparative studies have provided evidence of the equal effectiveness of low, medium and high doses of aspirin in patients with stroke or transient cerebrovascular accident (TCI) [2-4].

In a pooled analysis of the results of 21 studies on the secondary prevention of stroke or stroke, conducted in more than 18 thousand patients, the reduction in the risk of recurrent vascular events with antiplatelet therapy was 22% [1]. This avoided the development of 36 vascular complications, including 25 recurrent strokes and six myocardial infarctions, as well as seven cases of vascular and 15 total deaths per 1000 patients over two years. All these undoubted benefits were accompanied by an increase in the risk of major bleeding to 1-2 per 1000 patients per year. A dose of aspirin of 75 mg/day is considered minimally effective for the prevention of ischemic stroke (as for most cardiovascular diseases).

Until recently, the effectiveness and safety of aspirin administration in the acute phase of ischemic stroke have been little studied. Two large studies, CAST and IST, which included more than 40 thousand patients, confirmed the feasibility of using aspirin in the treatment of acute ischemic stroke [5, 6]. The drug was prescribed within 48 hours from the onset of symptoms of the disease, the dose was 160 and 300 mg/day, respectively, and the duration of treatment was two to four weeks. A pooled analysis of the CAST and IST trials found that immediate aspirin avoided nine deaths and recurrent nonfatal strokes in the first month and 13 deaths and permanent disability in the next six months per 1000 patients treated. The risk of developing hemorrhagic stroke was 2 per 1000 patients, and major bleeding - 3 per 1000.

Aspirin for atrial fibrillation

Atrial fibrillation (AF) is the main cause of embolic complications, primarily stroke, accounting for approximately 50% of cases [7]. The risk of developing ischemic stroke in patients with MA increases with age, as well as in the presence of concomitant cardiovascular diseases. Indirect anticoagulants are the absolute drugs of choice for MA. However, aspirin also turned out to be effective in patients with MA. According to five randomized trials, the reduction in the risk of vascular events with aspirin therapy was 24% [8]. Aspirin was found to be more effective in primary prevention of stroke in patients with MA than in secondary prevention [9].

Currently, aspirin is recommended for the primary prevention of stroke in patients with MA younger than 65 years of age, in the absence of cardiovascular diseases [10]. Also, the prescription of aspirin is possible for patients with an average risk of stroke (2-5% per year), if there is no more than one of the following factors: age 65-75 years, diabetes mellitus, coronary artery disease, thyrotoxicosis. In the presence of more than one of the above average risk factors, as well as left ventricular dysfunction, arterial hypertension, a history of stroke or embolism, mitral heart disease, or aged 75 years or older, the prescription of indirect anticoagulants is indicated [10]. The recommended dose of aspirin in patients with MA is 325 mg/day.

Aspirin for stable angina pectoris

Considering the rather low risk of developing vascular events in stable angina without a history of myocardial infarction (4-8% per year), for a long time it was not possible to obtain convincing evidence of the preventive effect of aspirin in these patients.

The clearest evidence of the effectiveness of aspirin in preventing MI and vascular death in patients with stable angina was obtained in the double-blind, placebo-controlled SAPAT study [11], which was conducted in 2035 patients receiving the β-blocker sotalol at an average dose of 160 mg. Aspirin was prescribed at a dose of 75 mg/day, the observation period was 50 months. When treated with aspirin, compared with placebo, the risk of MI and sudden death decreased by 34%, and vascular death, stroke and overall mortality - by 22-32%.

Aspirin for atherosclerotic lesions of the arteries of the lower extremities

Patients with atherosclerotic lesions of the arteries of the lower extremities (ALAD) represent a group at high risk of developing thrombotic complications. The results of prospective studies have shown that mortality in patients with APANC is two to four times higher than in an age- and sex-matched population [12, 13]. Combined damage to the coronary, brachiocephalic and lower extremity arteries, according to various studies, is observed in 20-50% of cases [14]. Atherosclerotic lesions of the coronary arteries of the heart, according to the results of coronary angiography, were noted in 90% of patients with APANK, while hemodynamically significant stenosis was observed in almost 60% [15]. Among the causes of death in patients with APANK, the first place is taken by ischemic heart disease (IHD) - 55%, followed by stroke - 10%, damage to vascular areas of other localization - 10%, other causes - 25% [12].

In a pooled analysis of the results of 42 studies, including 9214 patients with APANK (including those who had undergone angioplasty or bypass surgery of the arteries of the lower extremities), the administration of antiplatelet drugs reduced the total risk of developing vascular events by 23%, p-0.004 [1].

In the CAPRIE study [16], which compared the effectiveness of long-term use of clopidogrel and aspirin in various high-risk patients, the greatest reduction in the number of vascular events among those receiving clopidogrel was achieved in patients with APANK (23.8% vs 8.7% all patients). The higher effectiveness of thienopyridines (ticlopidine and clopidogrel) in patients with APANK, compared to other antiplatelet agents, can probably be explained by the fact that due to the large extent of atherosclerotic lesions and impaired rheological properties of the blood, the content of ADP released from erythrocytes is significantly increased. Thus, blockade of this platelet activation pathway may result in a greater reduction in the risk of blood clots.

Aspirin in patients with diabetes mellitus

Clinical manifestations of atherothrombosis are the direct cause of death in 80% of patients with diabetes mellitus, of which three quarters of cases are associated with ischemic heart disease. An analysis of nine studies in 4961 patients with diabetes showed that the reduction in the risk of developing vascular complications during antiplatelet therapy was only 7.8%, which is significantly less than among other high-risk patients (22%) [1]. The use of clopidogrel in patients with diabetes mellitus in the CAPRIE study allowed an additional avoidance of 21 vascular events in 1000 patients per year, and 38 in those requiring insulin, compared with aspirin [38]. Taking antiplatelet agents does not increase the risk of hemorrhages in the vitreous body and retina in patients with diabetes mellitus.

Aspirin during coronary artery bypass surgery

Prescribing aspirin in patients who have undergone coronary artery bypass grafting (CABG) can reduce the incidence of graft thrombosis by 50% [17]. However, until recently, there was no evidence of a positive effect of antithrombotic therapy on the risk of developing vascular events in these patients [1]. The majority of patients undergoing CABG are currently high-risk patients, in whom the incidence of postoperative complications exceeds 15% [18]. Moreover, these complications are associated not only with impaired cardiac function, but also with ischemia of the brain, kidneys, and intestines. A limitation to the use of antithrombotic drugs in the postoperative period may be the increased risk of hemorrhagic complications. In 2002, the results of a large, multicenter, prospective study [19] were published examining the effect of aspirin on the incidence of vascular events in more than 5000 patients undergoing CABG. In patients who received aspirin at a dose of 75-650 mg/day within 48 hours of revascularization, there was a significant reduction in the incidence of postoperative death, compared with those who were not prescribed aspirin (1.3% and 4%, p < 0.001, respectively). Taking aspirin was accompanied by a statistically significant reduction in the risk of developing myocardial infarction by 48%, stroke by 50%, renal failure by 74%, and intestinal infarction by 62%. Aspirin did not increase the risk of bleeding, gastrointestinal disorders, infection, or slow down the postoperative healing process. It should be noted that a significant decrease in the number of fatal and non-fatal complications was observed only among patients who received aspirin in the first 48 hours after surgery. Administration of the drug after 48 hours was accompanied by a non-significant reduction in postoperative mortality by 27%. There was also no dose-dependent antithrombotic effect of aspirin. This study confirmed the leading role of activation of the platelet component of hemostasis in the occurrence of dysfunction of vital organs in the postoperative period, as well as the fact that early administration of aspirin can be considered effective and safe in patients who have undergone CABG. However, among patients after CABG there is a high percentage of people with aspirin resistance, which may be due to the activation of cyclooxygenase-2 due to reparative processes.

Aspirin resistance

An important problem that attracts the interest of researchers is aspirin resistance, which is characterized by the inability of aspirin to prevent the development of thrombotic complications, as well as to adequately suppress the production of thromboxane A2. Resistance to aspirin is detected in 5-45% of patients, both among various groups of patients and in healthy individuals. Among the reasons for resistance to aspirin are considered: polymorphism and/or mutation of the cyclooxygenase-1 gene, the possibility of formation of thromboxane A2 in macrophages and endothelial cells via cyclooxygenase-2, polymorphism IIb/IIIa of platelet receptors, activation of platelets through other pathways that are not blocked by aspirin [20 ]. Unfortunately, very few studies have been conducted to evaluate the prognostic significance of laboratory-based aspirin resistance. Thus, the HOPE study showed that in patients with high urinary excretion of 11-dehydrothromboxane B2 (a stable metabolite of thromboxane A2), the risk of developing cardiovascular events was 1.8 times higher [21]. To date, no unified methods have been developed for assessing the antiplatelet effect of aspirin. Nevertheless, further study of this problem will contribute to the development of an individual approach to antithrombotic therapy, as well as increasing its effectiveness.

Aspirin and primary prevention of cardiovascular disease

The practice of primary prevention of cardiovascular diseases over the past 30 years has reduced mortality from coronary causes by 25% [22]. Aspirin is the only antithrombotic drug currently used for the primary prevention of cardiovascular disease. In what cases, when correcting major cardiovascular risk factors, is aspirin prescribed?

Suggestions that regular use of aspirin can reduce the risk of developing myocardial infarction and death from coronary causes appeared back in the 70s. [23-25]. Two large prospective studies were conducted in which aspirin was prescribed to female nurses without a previous coronary history and to patients with suspected CAD [26, 27]. The first study, which lasted for six years, was conducted on 87,678 women aged 34 to 65 years who regularly took one to six aspirin tablets per week [26]. The risk of non-fatal MI and coronary death was significantly reduced by 25%, in addition, there was a trend towards a decrease in death from vascular causes and the number of major vascular complications. It is interesting to note that the positive effect of aspirin was not pronounced in women under 50 years of age - the ratio of the number of vascular events among those who received and did not receive aspirin was 22 and 23 per 100 thousand. At the same time, in older age groups, the effectiveness of aspirin was significantly higher . Among women from 50 to 54 years of age, the incidence of vascular events in those who took and did not take aspirin was 62 and 121 per 100 thousand, and in the group from 55 years of age and above - 112 and 165 per 100 thousand, respectively. In another open-label study [27], among individuals in whom the diagnosis of coronary artery disease was not confirmed, aspirin administration reduced the risk of death in the group aged 60 years and above (5 and 8%, in those receiving and not receiving aspirin, respectively).

To date, there are data from five large controlled studies that examined the use of aspirin for primary prevention. These are American and English studies of doctors, Thrombosis Prevention Trial (TPT), Hypertension Optimal Treatment Study (HOT), Primary Prevention Project (PPP) [28-32].

A combined analysis of the results of American and English studies of doctors [33] revealed a significant reduction in the risk of non-fatal MI by 32%, and all vascular events by 13%. There was no significant effect of aspirin on overall and cardiovascular mortality, but there was a trend towards an increase in the incidence of non-fatal stroke. The dose of aspirin in these studies was 325 mg every other day and 500 mg/day, respectively. In an American study, aspirin administration avoided 4.4 myocardial infarctions per 1000 patients treated with this drug per year in the “older” age group, while the overall reduction was 1.9 per 1000 per year [28]. The effect of aspirin was also greater in individuals with diabetes mellitus, arterial hypertension, smokers and those leading a sedentary lifestyle [28].

In the TPT and HOT studies, aspirin was given at significantly lower doses of 75 mg/day. The TPT [30] included individuals at high risk of developing cardiovascular disease who received warfarin or aspirin monotherapy, a combination of warfarin and aspirin, and placebo. The number of fatal and non-fatal cases of coronary death during therapy with warfarin and aspirin decreased approximately equally - by 20%, while the effect of warfarin was mainly associated with a decrease in the incidence of fatal cases of coronary artery disease (39%), and aspirin - non-fatal cases (32%). The effect of aspirin was significantly greater in subjects with baseline systolic blood pressure ≤ 130 mm. rt. Art. (45% risk reduction) and was practically not observed with blood pressure ≥ 145 mm. rt. Art. (-6%) [34].

The HOT study was devoted to studying the effectiveness and safety of aspirin in patients with arterial hypertension under the conditions of selected antihypertensive therapy [31]. Prescription of aspirin reduced the risk of MI by 36%, and the total number of cardiovascular complications (MI, stroke, cardiovascular death) by 15%. The lowest incidence of cardiovascular events was observed when the mean diastolic blood pressure (DBP) reached 82.6 mm. rt. Art. the minimum risk of cardiovascular mortality at a DBP level is 86.5 mm. rt. Art. Further reductions in DBP were also safe. In patients with diabetes mellitus, the incidence of cardiovascular events on aspirin therapy decreased by 51% when DBP reached 80 mm. rt. Art. As in TPT, the HOT study did not show an increase in the total number of strokes with aspirin therapy.

Somewhat different are the results of the RRR study published in 2001 [32], in which aspirin was prescribed at a dose of 100 mg/day to patients with one or more risk factors for cardiovascular disease. The risk of developing MI and stroke decreased approximately equally - by 31 and 33%. There was a significant reduction in cardiovascular mortality by 44%, and all cardiovascular events (cardiovascular death, non-fatal MI and stroke, transient cerebrovascular accidents, stable angina, peripheral atherosclerosis) - by 23%.

In 2002, the results of a meta-analysis of five controlled trials on the primary prevention of cardiovascular events were published, which included more than 60 thousand patients [35]. It has been shown that the use of aspirin significantly reduces the risk of developing a first myocardial infarction by 32%, and the total number of vascular events by 15%. There was no statistically significant effect of aspirin on total mortality or total strokes, but the numbers were small in each of the studies pooled in the meta-analysis. The incidence of hemorrhagic stroke and gastrointestinal bleeding was higher in patients receiving aspirin. A meta-analysis of primary prevention studies found that aspirin avoided six to 20 myocardial infarctions in 1,000 patients with a 5% risk of vascular events over five years, but could cause between 0 and 2 more heart attacks. hemorrhagic strokes and two to four gastrointestinal bleedings [35].

Based on available data, taking aspirin for the purpose of primary prevention of cardiovascular events is recommended for patients with a risk of developing MI and ischemic stroke that exceeds the risk of possible complications (bleeding, hemorrhagic stroke, gastrointestinal disorders) [36, 37]. This group includes men and women over 50 years of age with at least one risk factor for coronary artery disease (hypercholesterolemia, diabetes mellitus, smoking, arterial hypertension). When prescribing aspirin to patients with arterial hypertension, blood pressure correction is necessary (maintaining DBP ≤ 85 mm Hg). The dose of aspirin considered effective for primary prevention is 75 mg/day.

The history of aspirin use goes back more than 100 years. Today, aspirin remains the most accessible and widely used antiplatelet drug used for both secondary and primary prevention of cardiovascular diseases. The clinical effectiveness of aspirin is confirmed by the results of numerous, controlled studies and meta-analyses. Importantly, the effectiveness of aspirin in reducing the cumulative incidence of myocardial infarction, stroke and cardiovascular mortality in high-risk groups remains independent of the emergence of new meta-analyses. Aspirin therapy can be considered as the standard of antithrombotic therapy, which is prescribed to all patients at high risk of developing vascular complications in the absence of contraindications. Of course, the prescription of aspirin, which blocks one pathway of platelet activation associated with inhibition of cyclooxygenase and the formation of thromboxane A2, does not help solve all the problems that arise during antithrombotic therapy. An important problem is aspirin resistance, which has been identified in a number of patients. Currently, there is an active search for antithrombotic drugs with different mechanisms of action that can enhance aspirin therapy in high-risk patients. The results of the CURE, CURE-PCI, CREDO studies convincingly demonstrated that taking a combination of aspirin and Plavix (clopidogrel) for 9-12 months leads to an additional reduction in the risk of developing vascular episodes in patients with ACS and after coronary balloon angioplasty. The effectiveness of platelet receptor IIb/IIIa inhibitors in interventions on the coronary arteries has also been demonstrated while taking aspirin. Antiplatelet drugs do not affect the coagulation cascade, the activation of which ultimately leads to increased thrombo- and fibrin formation, therefore, the combination of aspirin with indirect anticoagulants, an oral thrombin inhibitor - ximelagatran, as well as a newly created drug - seems promising in terms of preventing cardiovascular episodes. inhibitor of the factor VII/tissue factor complex.

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P. S. Laguta, Candidate of Medical Sciences E. P. Panchenko, Doctor of Medical Sciences, Research Institute of Cardiology named after. A. L. Myasnikova RKNPK Ministry of Health of the Russian Federation