Platelet aggregation inhibitor: indication, list, side effects

Aspirin, Plavix®… Platelet antiaggregants prevent platelets from sticking together. When are they prescribed? stroke? Heart attack? What are these drugs? What are the side effects and contraindications?

Definition: what is an antiplatelet agent?

It is a drug used for prevent the formation of blood clots that block the vessels. It does this by fighting platelet aggregation in the blood.

Indications: when to take an antiplatelet agent?

An antiplatelet agent prevents thromboembolic events (myocardial infarctionangina, stroke) and associated cardiovascular complications. Treatment is initiated after medical intervention (insertion of a stent, angioplastybridging) or after a recent stroke : myocardial infarction, stroke, PAD (obliterating arteriopathy of the lower limbs), unstable angina (angina), transient ischemic attack. Similarly, patients who present a high vascular risk are eligible for this treatment. In some cases, an antiplatelet agent may be prescribed as a substitute for vitamin K antagonist medication (anticoagulant) when contraindicated.

What is the mode of action of an antiplatelet agent?

An antiplatelet agent prevents platelet aggregation. The mechanism of action varies depending on the molecule.

► At low doses, acetylsalicylic acid (aspirin) blocks the action of platelet cyclo-oxygenase and thus reduces the production of thromboxane A2 (substance responsible for platelet aggregation and reduction in the caliber of blood vessels).

► At doses ≥ 500 mg/dose, this molecule presents properties painkillers due to a different mode of action.

► Medications Plavix® and Efient® act the same way. They are transformed into a product that blocks ADP binding (chemical substance) to its P2Y12 receptor located on the platelets. As for the drug Brilique®, it is directly active by binding to the P2Y12 receptor. It does not prevent ADP fixation but blocks the transmission of the signal to its receiver.
► In addition, Persantine® (dipyridamole) blocks ADP production and increases blood flow in the coronaries (arteries that supply the heart).
► Finally, ticlopidine prevents attachment of fibrinogen to its platelet receptor. Fibrinogen is a protein made by the liver that has a role in stopping bleeding.

What is the list of the main platelet aggregation inhibitors in France?

The main antiplatelet agents marketed in France are:

  • Acetylsalicylic acid : Acetylsalicylic acid Mylan, Aspirin Protect®, Kardegic® and Resitune®.
  • Clopidogrel : Plavix ® and generics
  • Ticagrelor : Brilique®
  • The prasugrel: Efient® and generics
  • Dipyridamole : Persantine®
  • Ticlopidine : Ticlopidine EG, Ticlopidine Arrow. The originator drug Ticlid® is no longer marketed.

The commercial specialty Duoplavin® contains a combination of acetylsalicylic acid and clopidogrel. Several generics are also available. The administration of Brilique® or Efient® is always coupled with acetylsalicylic acid. The choice of the molecule is made according to the type of vascular accident and the preventive effect sought.

What are the side effects of antiplatelet drugs?

All antiplatelet drugs can be responsible bleeding which are characterized in particular by bleeding nose, gums, stomach and intestine. Also, headaches and digestive disorders can be observed, except for Efient®. Digestive disorders include diarrhea, constipation, abdominal pain, ulcer or inflammation of the stomach lining, and intestinal discomfort. Adverse effects reported with acetylsalicylic acid are skin damage (urticaria, rash), a increased liver enzymes, a renal failure transient and the onset of a gout attack in predisposed individuals. The intensity and occurrence of digestive disorders are dependent on the dose administered. A kidney damage and hematomas have been reported with Plavix® (clopidogrel). The most common side effects seen with Brilique® are dizziness, loss of consciousness, low blood pressure and gout attacks. The occurrence of a anemia, bruising, blood in the urine and one skin rash is possible with Efient®. In addition, Persantine® (dipyridamole) may cause dizziness, angina pectoris, heart palpitations, skin rash associated with hives and muscle pain. Regarding ticlopidine-based medicines, they can cause decrease or absence of white blood cellsrash, dizziness, increased liver enzymes, cholesterol and triglycerides.

What are the contraindications of antiplatelet drugs?

Acetylsalicylic acid (aspirin) is contraindicated in many situations:

  • Disease caused by a nonsteroidal anti-inflammatory drug (including aspirin): asthma or history of asthma, history of digestive disease (ulcer, haemorrhage, perforation)
  • progressive peptic ulcer disease
  • Hemorrhagic disease or risk of bleeding.
  • Severe heart, liver or kidney failure
  • Mastocytosis (accumulation of a certain type of immune cells present in particular in the skin and bone marrow). In this case, the drug promotes the occurrence of severe allergic reactions.

This medicine is not contraindicated in pregnant women at low doses (anti-platelet aggregation dose). On the other hand, at analgesic or anti-inflammatory doses (≥ 500 mg per dose), it is formally prohibited from the 6th month of pregnancy.
► Taking Plavix® (clopidogrel) should be excluded in case of severe hepatic insufficiency and progressive diseases (intracranial hemorrhage, peptic ulcer).
► The drug Efient® (prasugrel) should not be administered in case of severe hepatic insufficiency, bleeding related to a disease or history of stroke or transient ischemic attack.
► Brilique® (ticagrelor) is strictly contraindicated in case of severe hepatic impairment, disease-related bleeding, or history of intracranial hemorrhage. In addition, it should not be combined with certain medications such as ketoconazole (mycosis treatment), clarithromycin (antibiotic), ritonavir (antiviral).
► Ticlopidine should be avoided in case peptic ulcer, recent stroke, certain blood diseases or deficiency or absence of white blood cells.
► The specialty Persantine® (dipyridamole) should not be taken by fructose intolerant patientshaving a glucose or galactose malabsorption syndrome, or having a deficiency of enzymes allowing the digestion of sugars.

Blood in the stool or urine, bleeding gums, abnormal fatigue or paleness of the face should lead the patient to consult

Is it compatible with anticoagulants?

Due to the increased risk of bleeding, the combination of an antiplatelet agent and an anticoagulant (oral or injectable) is not recommended. It is even not recommended for a patient with a stomach or duodenal ulcer. However, certain medical situations require the two drugs to be administered concomitantly. This is particularly the case of dipyridamole to be combined with an oral anticoagulant in a patient with a heart valve prosthesis. When an antiplatelet agent is prescribed with an anticoagulant, the occurrence of bleeding should be monitored. Indeed, hemorrhagic signs such as the presence of blood in the stool or urine, bleeding gums, abnormal fatigue or pallor of the face should lead the patient to consult a doctor as soon as possible.

– Public drug database. ANSM
– Platelet Aggregation Inhibitors, Pharmacomé

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