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Antiplatelet Medications

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Author: [Arshad Muhammad Iqbal](/content/point-of-care/17708#/ ""/index.html)Author: [Richard A. Lopez](/content/point-of-care/17708#/ ""/index.html)Editor: [Ofek Hai](/content/point-of-care/17708#/ ""/index.html)Updated: 11/7/2022 10:33:26 AM

Indications

Antiplatelet medications are divided into oral and parenteral agents. Oral agents subdivide further based on the mechanism of action. Aspirin was the first antiplatelet medication and is a cyclooxygenase inhibitor. Other oral antiplatelet agents include clopidogrel, ticagrelor, prasugrel, pentoxifylline, cilostazol, and dipyridamole. Glycoprotein IIb/IIIa inhibitors such as tirofiban and eptifibatide are only available as parenteral agents and are used in acute coronary syndrome (ACS). [[1]](/content/point-of-care/17708#ref_22315278 ""/index.html)

The following is a list of indications of antiplatelet medications:

  • Acute coronary syndrome
  • Post-percutaneous coronary intervention (PCI) with stenting
  • Mechanical heart valves in combination with warfarin
  • Acute ischemic stroke
  • Post-percutaneous intervention of peripheral arterial disease
  • Device closure of an atrial septal defect (ASD) for at least 6 months
  • Stable angina
  • Post-coronary artery bypass grafting surgery
  • Essential thrombocytosis
  • Primary prevention of coronary artery disease
  • Prevention of colon cancer
  • Kawasaki disease
  • Acute rheumatic disease
  • Post patent ductus arteriosus (PDA) device closure for the first 6 months
  • Acute pericarditis
  • Atrial fibrillation with a high risk of stroke
  • Primary prevention of venous thromboembolism

Mechanism of Action

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  • Occupational Medicine
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  • Ohio State CME CE Requirements
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  • Oncology
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  • Oral And Maxillofacial Surgery
  • Oregon State CME CE Requirements
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  • PA - Emergency Medicine End of Rotation
  • PA - End of Curriculum
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  • PA - Hospital Medicine (CAQ-HM®)
  • PA - Internal Medicine End of Rotation
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  • PA - Obstetrics and Gynecology (CAQ-OBGYN®)
  • PA - Occupational Medicine (CAQ-OM®)
  • PA - Orthopedic (CAQ-OS®)
  • PA - Palliative Medicine and Hospice Care (CAQ-PMHC®)
  • PA - PANCE®
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  • PA - Pediatric (CAQ-Peds®)
  • PA - Pediatric End of Rotation
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  • PA - Psychiatry (CAQ-Psy®)
  • PA - Surgery End of Rotation
  • PA - Womens Health End of Rotation (Gyn, Sexual, & Reproductive Health)
  • Pain Medicine
  • Pakistan - 1st Professional MBBS
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  • Pakistan FCPS Part I (Basic Science)
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  • Pennsylvania State CME CE Requirements
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  • Pharmacy - Certified Pharmacy Technician (PTCB® CPhT®)
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  • Pharmacy - Infectious Disease (BCIDP®)
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  • Pharmacy - Oncology (BCOP®)
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  • Physical Medicine and Rehabilitation
  • Physical Therapy - Geriatric Clinical Specialist (ABPTS® APTA® GCS)
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  • Physical Therapy - Physical Therapist (NPTE-PT)®
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  • Plastic Surgery
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Mechanism of Action

Antiplatelets can be classified based on the mechanism of action as follows:

  • Platelet aggregation inhibitors such as;
    • Aspirin and related cyclooxygenase inhibitors
    • Oral thienopyridines such as clopidogrel, ticagrelor, and prasugrel
  • Glycoprotein platelet inhibitors (eg, abciximab, eptifibatide, tirofiban)
  • Protease-activated receptor-1 antagonists (eg, vorapaxar)
  • Miscellaneous (eg, dipyridamole - a nucleoside transport inhibitor and phosphodiesterase type 3 (PDE3) inhibitor, cilostazol - also a PDE3 inhibitor) [[2]](/content/point-of-care/17708#ref_18827913 ""/index.html) [[3]](/content/point-of-care/17708#ref_19343166 ""/index.html)

Aspirin is the most commonly used oral antiplatelet drug. It irreversibly inhibits the cyclooxygenase enzyme (COX) activity in the prostaglandin synthesis pathway (PGH2). This prostaglandin is a precursor of thromboxane A2 (TXA2) and PGI2. Thromboxane A2 works by inducing platelet aggregation and vasoconstriction, and COX-1 mediates its production, while PGI2 works by inhibiting platelet aggregation, induces vasodilation, and is mediated by COX-2. Low-dose aspirin (75 mg to 150 mg) can induce complete or near-complete inhibition of COX-1, thus inhibiting the production of TXA2, while larger doses are required to inhibit COX-2. [[4]](/content/point-of-care/17708#ref_21320154 ""/index.html)

Oral thienopyridines selectively inhibit adenosine diphosphate-induced (ADP-induced) platelet aggregation. These drugs are converted into active drugs with the help of the hepatic CYP450 system that can irreversibly inhibit the platelet P2Y12 receptor. Prasugrel is the most potent of all 3 drugs, has a rapid onset of action, and is superior to clopidogrel in patients undergoing coronary stenting. Cangrelor is a new intravenous, reversible P2Y12 receptor antagonist with a rapid onset of action. It achieves a significant degree of platelet inhibition compared with clopidogrel. [[5]](/content/point-of-care/17708#ref_24393016 ""/index.html)

Glycoprotein platelet inhibitors work by inhibiting glycoprotein IIb/IIIa (GpIIb-IIIa) receptors on platelets, thus decreasing platelet aggregation. They are most commonly used in ACS.[3] These drugs are only available in an intravenous form and are, therefore, used as short-term therapy.

Dipyridamole has antiplatelet and vasodilating properties and inhibits platelet cyclic nucleotide phosphodiesterase. This enzyme is responsible for adenosine monophosphate (AMP) degradation to 5'AMP, which increases intra-platelet cyclic AMP accumulation and inhibits platelet aggregation. It also blocks the uptake of adenosine by the platelets, increasing cyclic AMP. [[6]](/content/point-of-care/17708#ref_6356465 ""/index.html)

Cilostazol is also reported to have vasodilatory, antiplatelet properties, and antiproliferative effects. It also reduces smooth muscle cell hyperproliferation and intimal hyperplasia after an injury to the endothelium. [[7]](/content/point-of-care/17708#ref_16275169 ""/index.html)

Administration

Antiplatelet agent administration can be via oral, rectal, or intravenous routes. Oral medications include aspirin, clopidogrel, ticagrelor, cilostazol, and dipyridamole. Intravenous drugs include GpII-IIIA inhibitors and can be used for a short period, most commonly during acute coronary syndromes before or during PCI. Aspirin is available as a rectal suppository if the patient cannot take the drug orally. The articles for each drug on the Statpearls platform cover individual agent dosing. The reader is advised to seek those articles out for specific dosing information.

Adverse Effects

The following are the most common adverse effects associated with antiplatelet medications:

  • Aspirin-induced asthma
  • Nasal polyps
  • Upper gastrointestinal bleeding because of chronic gastritis
  • Ecchymosis
  • Hematuria
  • Epistaxis
  • Ticagrelor-related dyspnea
  • Hemorrhage
  • Thrombocytopenia [[8]](/content/point-of-care/17708#ref_21912415 ""/index.html)

Cilostazol's most common side effects are headache, nausea, diarrhea, pain, infection, upper respiratory symptoms, palpitations, arrhythmias, and peripheral edema.

Contraindications

The most common contraindications for using antiplatelet agents are as follows:

  • Large esophageal varices
  • Recent stroke within 2 years
  • History of intracranial hemorrhage
  • Significant thrombocytopenia
  • Major surgery within 72 hours
  • Hypersensitivity to the medication
  • Acute clinically significant bleed
  • End-stage renal disease on hemodialysis
  • Decompensated liver cirrhosis
  • Severe hypertension with a BP over 200/110 mmHg
  • Congestive heart failure is a contraindication for the use of cilostazol [[9]](/content/point-of-care/17708#ref_27245070 ""/index.html)

Monitoring

Before starting antiplatelet agents, the patient should undergo an assessment for bleeding risk. Advanced age, female gender, and impaired renal function are important factors. The patient should know antiplatelet agents' risks, benefits, and alternatives. Monitoring is generally not required for antiplatelet medications; however, if bleeding is present, bleeding time is helpful to determine if a platelet transfusion is needed or if the medication requires discontinuation. In life-threatening bleeding, such as massive upper gastrointestinal bleeding, the clinician should stop the drug as soon as possible. If the antiplatelet is an essential therapy, such as in post-coronary stenting patients, the medications should be resumed as quickly as safely possible.

The use of concomitant anticoagulants should be minimized as much as possible, as they increase the risk of bleeding by many times. Clopidogrel and ticagrelor should be discontinued for at least 5 days, and prasugrel should be discontinued for at least 7 days before major cardiac or non-cardiac surgery.

Toxicity

Aspirin is the most commonly used of all antiplatelet drugs, so accidental intake is common. The effect can be life-threatening if taken over 150 mg/kg of body weight. Supportive measures to decrease the absorption of the drug are achievable by using activated charcoal, but only if administered within 4 hours of ingestion. The patient needs monitoring for signs and symptoms of bleeding and the development of metabolic derangements, such as acidosis. If acidosis develops, immediate dialysis is indicated. [[10]](/content/point-of-care/17708#ref_11971828 ""/index.html) No antidote is available for most of these drugs; however, a monoclonal antibody against ticagrelor is in development, but it is not commercially available yet.

Enhancing Healthcare Team Outcomes

Antiplatelet drug therapy requires an interprofessional team approach, including clinicians (MDs, DOs, NPs, PAs), specialty-trained nurses, and pharmacists. To achieve optimal patient results, these professionals must collaborate and engage in open communication.

The choice of an antiplatelet agent depends on the clinical situation. Because of the availability of many antiplatelet agents, the ordering/prescribing clinician should consult with a cardiology or pharmacotherapy specialized pharmacist. When prescribing these agents, the pharmacist should review the patient's medication list and past diagnoses to determine if specific agents are recommended or contraindicated. Communication between the clinical provider and the pharmacists is essential to minimize adverse patient outcomes when using these drugs. A cardiac pharmacist can offer direction regarding agent selection, drug-drug interactions, dose verification, and medication reconciliation for high-risk patients.

The role of the cardiac nurse administering these medications in the acute setting involves monitoring for any acute adverse symptoms. Prompt communication by the astute nursing staff of an adverse reaction or a complication can significantly reduce patient morbidity and mortality.

Nurses are often the first healthcare providers to verify these agents' therapeutic effectiveness and monitor for adverse effects. This role becomes crucial in patients receiving dual antiplatelet therapy, as is often the case for preventing stent thrombosis or after an ACS event. The specialty-trained clinicians educate the patient on possible complications, the indications for the prescribed therapy, and the need for adherence to the medication treatment regimen. The nurse should communicate with the clinical provider and the pharmacist if noting any adverse reaction or if there is a concern for patient adherence to drug therapy so that alternative therapies can be considered. An interprofessional approach, with a multifaceted and targeted approach to treatment, is necessary to improve patient outcomes with antiplatelet medications.

References

[1]

Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb:141(2 Suppl):e89S-e119S. doi: 10.1378/chest.11-2293. Epub [PubMed PMID: 22315278]

Level 1 (high-level) evidence

[2]

Krötz F, Sohn HY, Klauss V. Antiplatelet drugs in cardiological practice: established strategies and new developments. Vascular health and risk management. 2008:4(3):637-45 [PubMed PMID: 18827913]

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Hashemzadeh M, Furukawa M, Goldsberry S, Movahed MR. Chemical structures and mode of action of intravenous glycoprotein IIb/IIIa receptor blockers: A review. Experimental and clinical cardiology. 2008 Winter:13(4):192-7 [PubMed PMID: 19343166]

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Warner TD, Nylander S, Whatling C. Anti-platelet therapy: cyclo-oxygenase inhibition and the use of aspirin with particular regard to dual anti-platelet therapy. British journal of clinical pharmacology. 2011 Oct:72(4):619-33. doi: 10.1111/j.1365-2125.2011.03943.x. Epub [PubMed PMID: 21320154]

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Kubica J, Kozinski M, Navarese EP, Tantry U, Kubica A, Siller-Matula JM, Jeong YH, Fabiszak T, Andruszkiewicz A, Gurbel PA. Cangrelor: an emerging therapeutic option for patients with coronary artery disease. Current medical research and opinion. 2014 May:30(5):813-28. doi: 10.1185/03007995.2014.880050. Epub 2014 Jan 24 [PubMed PMID: 24393016]

Level 3 (low-level) evidence

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Harker LA, Kadatz RA. Mechanism of action of dipyridamole. Thrombosis research. Supplement. 1983:4():39-46 [PubMed PMID: 6356465]

Level 3 (low-level) evidence

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Goto S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atherosclerosis. Supplements. 2005 Dec 15:6(4):3-11 [PubMed PMID: 16275169]

[8]

Kalyanasundaram A, Lincoff AM, Medscape. Managing adverse effects and drug-drug interactions of antiplatelet agents. Nature reviews. Cardiology. 2011 Sep 13:8(10):592-600. doi: 10.1038/nrcardio.2011.128. Epub 2011 Sep 13 [PubMed PMID: 21912415]

[9]

Barnes GD, Stanislawski MA, Liu W, Barón AE, Armstrong EJ, Ho PM, Klein A, Maddox TM, Nallamothu BK, Rumsfeld JS, Tsai TT, Bradley SM. Use of Contraindicated Antiplatelet Medications in the Setting of Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation. Cardiovascular quality and outcomes. 2016 Jul:9(4):406-13. doi: 10.1161/CIRCOUTCOMES.115.002043. Epub 2016 May 31 [PubMed PMID: 27245070]

Level 2 (mid-level) evidence

[10]

Dargan PI, Wallace CI, Jones AL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emergency medicine journal : EMJ. 2002 May:19(3):206-9 [PubMed PMID: 11971828]

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