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ARTICLE INFO
CLINICAL PHARMACOLOGICAL APPROACH TO THE USE OF ANTICOAGULANT DRUGS IN ISCHEMIC HEART
DISEASE Akhmedov Bahodir Urolovich
Assistant intern at the Department of "Pharmacology, clinical pharmacology and medical biotechnologies", ASMI https://doi.org/10.5281/zenodo.14557074
ABSTRACT
Received: 19th December 2024 Accepted: 25th December 2024 Online: 26th December 2024
KEYWORDS Ischemic heart disease, non-valvular atrial fibrillation, anticoagulants, antiplatelet therapy.
The article discusses approaches to the choice of antithrombotic therapy (AT) in patients with non-valvular atrial fibrillation (AF) and coronary heart disease (CHD) both in acute coronary syndrome (ACS) and stable forms, including those who have undergone percutaneous coronary intervention. Determination of the regimens and duration of AT depend on the form of CHD, the risk of bleeding, and the anatomy of the implanted stents in the coronary arteries. In the composition of AT in modern regulatory documents, any oral anticoagulant is recommended for patients with CHD and AF: vitamin K antagonists, direct thrombin inhibitor - dabigatran, selective factor Xa inhibitors of coagulation - rivaroxaban, apixaban.
INTRODUCTION
According to the European registry EORP-AF (EURObservational Research Programme Atrial Fibrillation), which included 3119 patients with AF aged 68.8 years, including 40.4% women; the incidence of coronary heart disease was 36.4% and did not depend on the form of arrhythmia [1]. At the same time, 70.9% of patients were diagnosed with arterial hypertension (AH), 44.8% of patients had myocardial infarction (MI), 47% of the subjects underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting, 37.7% had symptoms of angina pectoris, 47.5% had signs of chronic heart failure (CHF), with 41.2% having functional classes III-IV. In another observational study PREFER in AF (PREvention oF thromboemolic events — European Registry in Atrial Fibrillation), which involved 7 European countries, it was noted that the incidence of coronary heart disease in patients with AF is recorded at 23.4% and is accompanied in 21.3% of cases by clinically expressed CHF, while 10.7% of patients suffered an MI, and 10.2% underwent PCI [2]. The international registry CLARIFY (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease) included 33,428 patients with coronary heart disease (32,954 available for analysis), of which 2,229 (6.7%) patients had documented AF [3]. The average score among these patients on the CHA2DS2-VASc scale (Congestive Heart failure, Hypertension, Age (2 points), Diabetes mellitus, Stroke (2 points), Vascular disease, Age, Sex category) was 4.
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MATERIALS AND METHODS
AF is not only the most common arrhythmia preceding MI, but also a frequent complication [4]. In patients with MI who undergo a reperfusion strategy using thrombolytic therapy, AF develops with a frequency of 5% to 10% of cases. The occurrence of AF in the post-infarction period is more common in elderly patients, patients with CHF and after extensive MI. The DIAMOND (Danish Investigations of Arrhythmia and Mortality ON Dofetilide) study included 2,627 patients with left ventricular dysfunction over 42 months, some of whom developed this pathology against the background of MI [5]. The incidence of AF in the acute period of MI among these patients was 2.9%. In the American population of patients with acute coronary syndrome (ACS), the frequency of concomitant AF was 21.7%
[3].
There are well-known scientific facts confirmed by clinical practice, which argue that the combination of AF and IHD, especially in the case of ACS, is always accompanied by a worsening prognosis and an increased risk of developing not only ischemic events, but also thromboembolic complications with a fatal outcome [4].
A significant negative impact on the development of MI and stroke in patients with IHD and AF is caused by the problems of choosing antithrombotic therapy (AT), especially in the context of ACS and/or performing PCI in stable IHD [3].
On the one hand, patients with IHD require antiplatelet therapy, including dual therapy, in order to prevent MI, the need for revascularization, and stent thrombosis during PCI. On the other hand, in patients with AF, anticoagulants must be used to prevent stroke and systemic embolism. Accordingly, a combination of antiplatelet drugs and an anticoagulant prescribed to patients with coronary heart disease and AF may lead to an increased risk of bleeding, including the most dangerous - intracranial [4].
RESULTS AND DISCUSSION
In recent years, a number of such RCTs have been initiated. The REDUAL PCI (Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) study in patients with stable coronary artery disease or with ACS and AF after PCI will evaluate the safety and efficacy of the oral anticoagulant dabigatran at doses of 150 and 110 mg twice daily in comparison with warfarin in combination with clopidogrel or ticagrelor, as well as triple AT (warfarin, aspirin, P2Y12 inhibitor) [4]. Other studies, such as AUGUSTUS (Study Apixaban to Vitamin K Antagonist for the Prevention of Stroke or Systemic Embolism and Bleeding in Patients With Non-valvular Atrial Fibrillation and Acute Coronary Syndrome/Percutaneous Coronary Intervention), PIONEER AF-PCI (A Study Exploring Two Strategies of Rivaroxaban and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), OAC-ALONE (Optimizing Antithrombotic Care in Patients With AtriaL fibrillatiON and Coronary stEnt Study) will determine the efficacy and safety of oral anticoagulants in double or triple combination with various antiplatelet drugs in patients with chronic and acute forms of coronary artery disease who underwent PCI and with AF [5]. The results of these RCTs will provide the possibility of an effective and safe choice of AT in patients with coronary artery disease and AF. According to the Consensus, in order to minimize the risks of bleeding and maintain the effectiveness of AT in terms of improving the prognosis of a patient with AF in
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the acute period of STEMI, primary PCI can be performed using aspirin, clopidogrel, unfractionated heparin or bivalirudin (class of evidence IIb, level B). With a high risk of bleeding, calculated according to the HAS-BLED scale (Hypertension, Abnormal renal-liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (65 years), Drugs or alcohol concomitantly), when using such combinations, it might be advisable to temporarily suspend the use of oral anticoagulants (class of evidence IIb, level B). Routine use of GPIIB/IIIa platelet receptor inhibitors before PCI, as well as P2Y12 inhibitors such as ticagrelor, prasugrel, is not desirable. It should be noted that in primary PCI in a patient with STEMI, radial access should be considered as the safest, providing prevention of bleeding during the PCI procedure (class of evidence I, level B). At the same time, in patients with a low risk of bleeding (HAS-BLED = 0-2), a new generation of drug-eluting stents may be preferable to non-drug-eluting stents (class of evidence IIb, level C).
When determining the need, choice of oral anticoagulants and antiplatelet drugs, their duration for a patient with STEMI against the background of AF, one should be guided by the level of bleeding risk in each individual patient, assessed by the HAS-BLED scale. With a low bleeding risk (HAS-BLED 0-2), a patient with STEMI and AF is recommended to initiate triple AT (oral anticoagulant, aspirin, clopidogrel) for 6 months, and after PCI, the duration of therapy does not depend on the type of stent, with subsequent transition to long-term, up to 12 months, therapy using a combination of an anticoagulant and clopidogrel at a dose of 75 mg / day. An alternative to clopidogrel can be aspirin at a dose of 75-100 mg / day. As anticoagulant therapy, both the direct thrombin inhibitor dabigatran and the selective factor Xa inhibitors rivaroxaban and apixaban can be used. Vitamin K antagonists can be used only if a stable international normalized ratio (INR) is maintained, when the time in the therapeutic range during their use is >70% (evidence class IIa, level C). Platelet P2Y12 receptor inhibitors (prasugrel and ticagrelor) should not be prescribed as part of triple therapy in patients with MI and AF (evidence class III, level C).
In patients with high risk of bleeding (HAS-BLED 3) with STEMI and AF, as presented in the Consensus, it is necessary to consider, starting from the acute period, the use of triple therapy - an oral anticoagulant, aspirin, clopidogrel, only for 4 weeks, during PCI regardless of the type of stent, with subsequent transition to dual therapy (up to 12 months), including an oral anticoagulant and clopidogrel at a dose of 75 mg / day. or alternatively aspirin at a dose of 75-100 mg / day. Among anticoagulants, both new oral anticoagulants and vitamin K antagonists can also be used, provided that a stable INR is maintained (class of evidence IIa, level C). As an alternative to initial triple AT in certain categories of patients with a high risk of bleeding (HAS-BLED >3) and a low risk of stent thrombosis/recurrent ischemic event, it is possible to consider the use of dual therapy consisting of any oral anticoagulant and clopidogrel at a dose of 75 mg/day. (Class of evidence IIb, Level C).
During the period of combined AT, especially in patients with a high risk of bleeding (HAS-BLED >3), the Consensus notes that the appointment of proton pump inhibitor therapy should be considered, which can reduce the risk of gastroduodenal bleeding (Class of evidence IIa, Level C).
In the future, if no ischemic or thromboembolic events are recorded during the year after STEMI against the background of AF, then long-term monotherapy with oral
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