Antiplatelet Medications

Article Author:
Arshad Muhammad Iqbal
Article Author (Archived):
Richard Lopez
Article Editor:
Ofek Hai
8/30/2019 1:32:15 PM
PubMed Link:
Antiplatelet Medications


Antiplatelet medications divide into oral and parenteral agents. Oral agents subdivide further based on the mechanism of action. Aspirin is the first antiplatelet medication and is a cyclooxygenase inhibitor. Others oral antiplatelet include clopidogrel, ticagrelor, and prasugrel, pentoxifylline, cilostazol, and dipyridamole. Glycoprotein IIb/IIIa inhibitors such as tirofiban, eptifibatide are only available as parenteral agents and used in acute phases of acute coronary syndrome (ACS).[1]

Following are a few indications of antiplatelet medications: 

  • Acute coronary syndrome
  • Post percutaneous coronary intervention with stenting
  • Mechanical heart valves in combination with warfarin
  • Acute ischemic stroke
  • Post percutaneous intervention of peripheral arterial disease
  • Device closure such as post ASD closure for at least six 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 PDA device closure for the first six months
  • Acute pericarditis
  • Atrial fibrillation with a CHAD2SVASc score of 1
  • Primary prevention of venous thromboembolism

Mechanism of Action

The major classes of an antiplatelet agent based on the mechanism of action are as follows[2][3][2]:

  • Platelet aggregation inhibitors such as;
    • Aspirin and related cyclooxygenase inhibitors
    • Oral thienopyridines such as clopidogrel, ticagrelor, ticlopidine, and prasugrel
  • Glycoprotein platelet inhibitors (e.g., abciximab, eptifibatide, tirofiban)
  • Protease-activated receptor-1 antagonists (e.g. vorapaxar)
  • Miscellaneous (e.g., dipyridamole, cilostazol)

Aspirin is the most commonly used oral antiplatelet drug. It works by irreversibly inhibiting COX activity of the prostaglandin synthesis PGH2. This prostaglandin is a precursor of thromboxane A2 and PGI2. Thromboxane A2 works by inducing platelets aggregation and vasoconstriction, and COX-1 inhibits its production while PGI2 works by inhibiting platelets aggregation and induces vasodilation and inhibited by COX-2. Low dose aspirin (75-150mg) can induce complete or near-complete inhibition of COX-1, thus inhibits the production of TXA2 while larger doses are required to inhibit CoX-2.[4]

Oral thienopyridines selectively inhibit ADP-induced platelet aggregation. These drugs convert to an active drug with the help of hepatic CYP450 system that inhibits the platelet P2Y12 receptor. Prasugrel is the most potent of all three drugs, has a rapid onset of action and is superior to clopidogrel in patients undergoing coronary stenting. Ticlopidine has fallen out of favor because of bone marrow toxicity. Cangrelor is a new intravenous, reversible P2Y12 receptor antagonist and has a rapid onset of action. It achieves a significant level of platelet inhibition compared with clopidogrel.[5]

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

Dipyridamole has antiplatelet and vasodilating properties and inhibits platelet cyclic nucleotide phosphodiesterase. This enzyme is responsible for the degradation of AMP to 5' AMP, which increases intra-platelet cyclic AMP accumulation and inhibits platelets aggregation. It also blocks the uptake of adenosine by the platelets, which also increase cyclic AMP.[6]

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]


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.

Adverse Effects

Following are the most common adverse effects associated with antiplatelet medications.[8]

  • Aspirin-induced asthma
  • Nasal polyps
  • Upper gastrointestinal bleeding because of chronic gastritis
  • Ecchymosis
  • Hematuria
  • Epistaxis
  • Ticagrelor-related dyspnea
  • Hemorrhage
  • Thrombocytopenia

Headache, nausea, diarrhea, pain, infection, upper respiratory symptoms, palpitations, arrhythmias, and peripheral edema are the most common side effects associated with cilostazol.


Most common contraindications of antiplatelet agents are as follows[9]:

  • Large esophageal varices
  • Recent stroke within two years
  • History of intracranial hemorrhage 
  • Significant thrombocytopenia 
  • Major surgery with 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
  • Congestive heart failure is a contraindication for the use of cilostazol


Before starting antiplatelet agents, the patient should undergo assessment for bleeding risk. Advanced age, female gender, and impaired renal function are important factors to consider. The patient should be aware of the risks, benefits, and alternatives of antiplatelet agents. Monitoring is generally not required for antiplatelet medications; however, if bleeding is present, bleeding time will be useful to determine if a platelet transfusion is needed or if the medication requires discontinuation. In life-threatening bleeding such as massive upper GI bleed, the physician should stop the drug as soon as possible. If the antiplatelet is an essential therapy such as in post-stenting patients, the medications should be resumed as quickly as safely possible. The use of concomitant anticoagulant should be minimized as much as possible as it will increase the risk of bleeding by many times. Discontinuance of clopidogrel and ticagrelor should be at least five days and prasugrel at least seven days before major cardiac or non-cardiac surgery. 


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 the body weight. Supportive measure to decrease the absorption of the drug can are achievable by using activated charcoal but only if administered within 4 hours of ingestion. The patient will need monitoring for signs and symptoms of bleeding and development of metabolic derangement such as acidosis. If acidosis develops, immediate dialysis is mandatory.[10] There is no antidote available for most of these drugs; however, a monoclonal antibody against ticagrelor is in development, but it is not widely available yet.

Enhancing Healthcare Team Outcomes

The choice of an antiplatelet agent depends on the clinical situation. Because of the availability of a large number of antiplatelet agents, the ordering/prescribing physician should request pharmacist consultation for the drugs currently recommended, based on clinical trial data. The pharmacist can offer direction regarding agent selection, drug-drug interactions, dose verification, and overall medication reconciliation. The pharmacist will report any concerns to the healthcare team promptly.

Nursing will often administer the drugs (inpatient) or offer counsel along with the prescribing physician when prescribing outpatient or after day surgery. Nurses are often the first line to verify therapeutic effectiveness and monitor for adverse effects from the antiplatelet drug therapy.

Dual antiplatelet therapy is essential if given for the prevention of stent thrombosis. The patient should receive education for compliance as compliance is the critical factor in the prevention of these events. The physician should avoid giving medications which decrease the effect of thienopyridines. Aspirin and thienopyridines have correlations with reduced mortality after an acute coronary syndrome; however, cilostazol has no mortality benefit but improves morbidity by increasing functional platelet drug capacity and improving symptoms.

As can be seen from the above, antiplatelet drug therapy requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]


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