Anticoagulants and Antiplatelets in the Treatment of Acute Coronary Syndromes
Anticoagulants and antiplatelets are a key part of the therapeutic strategies used in the treatment of acute coronary syndromes (ACS). They reduce the risk of acute and late complications, morbidity, and mortality in patients. On the other hand, their main disadvantage is the potential occurrence of bleeding complications. Therefore, the goal of physicians is to use these medications appropriately, maximizing benefits for patients while minimizing the risk of bleeding.
Acute Coronary Syndrome
Patients with ACS are at significant risk of serious complications; therefore, diagnostic and treatment procedures need to be very swift and accurate. The dominant symptom is chest pain with all typical attributes. After taking the patient’s history, performing a physical examination, and evaluating the EKG findings, patients can be classified into groups with ST-segment elevation (STEMI), without ST-segment elevation (NSTEMI), or groups where ACS is unlikely. As soon as possible after the first contact with the patient, blood samples are taken to determine specific cardiac markers. The patient is then placed on a monitored bed and initial therapy is started, including the administration of oxygen, nitrates, antiplatelets, anticoagulants, analgesics, and other medications as needed. Simultaneously, based on risk stratification, we aim towards either invasive or conservative therapy.
Antithrombotic Therapy in Patients with ACS Without ST Elevation
Antiplatelet and anticoagulant therapy is absolutely necessary for all patients suspected of ACS, both in cases aimed at invasive treatment and without it. However, the form, duration, and combination of pharmacotherapy depend on several factors specific to the individual.
Antiplatelets
Standard dual antiplatelet therapy involves acetylsalicylic acid (ASA) and a P2Y12 receptor inhibitor. ASA administration starts with a loading dose of 150–300 mg orally or 75–250 mg intravenously, followed by a long-term maintenance dose of 75–100 mg orally once daily. Along with ASA, a P2Y12 receptor inhibitor is used for 12 months, which prevents platelet activation by binding to this receptor. Prasugrel is preferred in patients expected to undergo early invasive procedures. Care should be taken when using it in patients weighing < 60 kg, older than 75 years, and it is contraindicated in patients with a history of stroke. Ticagrelor can be administered regardless of the planned treatment strategy, supported by data from the PLATO study, which showed fewer ACS complications compared to clopidogrel. Clopidogrel is recommended if other drugs in this group are unavailable or contraindicated.
Anticoagulants
Alongside antiplatelet therapy, parenteral anticoagulant therapy is also recommended. Unfractionated heparin is started with an initial dose of 70–100 IU/kg, followed by continuous intravenous infusion until percutaneous coronary intervention (PCI) if an invasive approach is planned.
Among low molecular weight heparins (LMWH), enoxaparin is primarily used. Its administration is preferred in patients expected to undergo conservative ACS treatment. Advantages of enoxaparin include better subcutaneous absorption, lower binding to plasma proteins, and thus a more predictable therapeutic effect. Monitoring of treatment through laboratory determination of anti-Xa is recommended only in patients with renal insufficiency and some obese or elderly patients. Studies ESSENCE and TIMI 11B have shown better results for enoxaparin compared to unfractionated heparin in conservatively treated patients. Additional studies (SYNERGY and EXTRACT-TIMI 25) explored bleeding risk comparisons. Higher bleeding complications with enoxaparin were observed, but this finding was not statistically significant.
The recommended dose of enoxaparin for treating unstable angina and NSTEMI is 100 IU/kg subcutaneously every 12 hours. The usual duration of treatment is 2–8 days. It is contraindicated in patients with end-stage renal disease, and dose adjustments are needed in patients with renal impairment.
For patients with high bleeding risk and planned conservative treatment, fondaparinux may also be considered.
Conclusion
The approaches used in the treatment of acute coronary syndrome are continually being refined and developed. The goal of research and clinical practice is to balance the benefits of antithrombotic therapy with the increased risk of bleeding and its consequences. Therapy selection should respect the pharmacokinetics and pharmacodynamics of available drugs and take into account external and internal factors specific to each patient.
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Sources:
1. Singh D., Gupta K., Vacek J. L. Anticoagulation and antiplatelet therapy in acute coronary syndromes. Cleveland Clin J Med 2014; 81 (2): 103–114, doi: 10.3949/ccjm.81a.13016.
2. Moťovská Z., Kala P., Hutyra M., Hromádka M. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, 2020. Summary document prepared by the Czech Society of Cardiology. Cor et Vasa 2021; 63: 197–234.
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