An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
that decrease
platelet aggregation
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and inhibit
thrombus
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
formation. They are effective in the
arterial
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pul ...
circulation where
anticoagulants
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
have little effect.
They are widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease.
Antiplatelet therapy with one or more of these drugs decreases the ability of blood clots to form by interfering with the platelet activation process in primary
hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, whi ...
.
Antiplatelet drugs can reversibly or irreversibly inhibit the process involved in platelet activation resulting in decreased tendency of platelets to adhere to one another and to damaged blood vessels' endothelium.
Choice
A 2006 review states: "...low-dose aspirin increases the risk of major bleeding 2-fold compared with
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
. However, the annual incidence of major bleeding due to low-dose aspirin is modest—only 1.3 patients per thousand higher than what is observed with placebo treatment. Treatment of approximately 800 patients with low-dose aspirin annually for cardiovascular prophylaxis will result in only 1 additional major bleeding episode."
Dual antiplatelet therapy
Often a combination of aspirin plus an
ADP/P2Y inhibitor
(such as
clopidogrel
Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following t ...
,
prasugrel
Prasugrel, sold under the brand name Effient in the US, Australia and India, and Efient in the EU) is a medication used to prevent formation of blood clots. It is a platelet inhibitor and an irreversible antagonist of P2Y12 ADP receptors and is ...
,
ticagrelor
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It ...
, or another) is used in order to obtain greater effectiveness than with either agent alone. This is known as "dual antiplatelet therapy" (or DAPT).
Classification
Classes of antiplatelet drugs include:
*Irreversible
cyclooxygenase
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prosta ...
inhibitors
**
Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
**
Triflusal (Disgren)
*
Adenosine diphosphate (ADP) receptor inhibitor
Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute coronary syndrome (ACS) or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a ...
s
**
Cangrelor
Cangrelor, sold under the brand name Kengreal in the United States, CANREAL in India ( MSN Labs ) and Kengrexal in the European Union) is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P ...
(Kengreal)
**
Clopidogrel
Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following t ...
(Plavix)
**
Prasugrel
Prasugrel, sold under the brand name Effient in the US, Australia and India, and Efient in the EU) is a medication used to prevent formation of blood clots. It is a platelet inhibitor and an irreversible antagonist of P2Y12 ADP receptors and is ...
(Effient)
**
Ticagrelor
Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It ...
(Brilinta)
**
Ticlopidine
Ticlopidine, sold under the brand name Ticlid, is a medication used to reduce the risk of thrombotic strokes. It is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Research initially s ...
(Ticlid)
*
Phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cycli ...
s
**
Cilostazol
Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. If no improvement is seen after 3 months, stopping the medication is reasonable. It ...
(Pletaal)
*Protease-activated receptor-1 (PAR-1) antagonists
**
Vorapaxar
Vorapaxar (brand name Zontivity, formerly known as SCH 530348) is a thrombin receptor (protease-activated receptor, PAR-1) antagonist based on the natural product himbacine, discovered by Schering-Plough and developed by Merck & Co.
Medical use ...
(Zontivity)
*
Glycoprotein IIB/IIIA inhibitor In medicine, glycoprotein IIb/IIIa inhibitors, also GpIIb/IIIa inhibitors, is a class of antiplatelet agents.
Several GpIIb/IIIa inhibitors exist:
* abciximab (abcixifiban) (ReoPro)
* eptifibatide (Integrilin)
* tirofiban (Aggrastat)
* roxifiban ...
s (intravenous use only)
**
Abciximab
Abciximab, a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures lik ...
(ReoPro)
**
Eptifibatide
Eptifibatide (Integrilin, Millennium Pharmaceuticals, also co-promoted by Schering-Plough/Essex), is an antiplatelet drug of the glycoprotein IIb/IIIa inhibitor class. Eptifibatide is a cyclic heptapeptide derived from a disintegrin protein () ...
(Integrilin)
**
Tirofiban
Tirofiban, sold under the brand name Aggrastat, is an antiplatelet medication. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibr ...
(Aggrastat)
*
Adenosine reuptake inhibitor
An adenosine reuptake inhibitor (AdoRI) is a type of drug which acts as a reuptake inhibitor for the purine nucleoside and neurotransmitter adenosine by blocking the action of one or more of the equilibrative nucleoside transporters (ENTs). This i ...
s
**
Dipyridamole
Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a s ...
(Persantine)
*
Thromboxane inhibitor
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring.
Thromboxane is named for its ...
s
**
Thromboxane synthase inhibitors
Thromboxane A synthase 1 (, platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the ''TBXAS1'' gene.
Function
This gene encodes a member of the cytochrome P450 supe ...
**
Thromboxane receptor antagonist
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the ''TBXA2R'' gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid rec ...
s
***
Terutroban
Terutroban is an antiplatelet agent developed by Servier Laboratories. It is a selective thromboxane prostanoid (TP) antagonist and is an orally active drug in clinical development for the secondary prevention of acute thrombotic complications. ...
Usage
Prevention and treatment of arterial thrombosis
Prevention and treatment of arterial thrombosis is essential in patients with certain medical conditions whereby the risk of thrombosis or thromboembolism may result in disastrous consequences such as heart attack, pulmonary embolism or stroke.
Patients who require the use of antiplatelet drugs are: stroke with or without atrial fibrillation, any heart surgery (especially prosthetic replacement heart valve), Coronary Heart Disease such as stable angina, unstable angina and heart attack, patients with coronary stent, Peripheral Vascular Disease/Peripheral Arterial Disease and apical/ventricular/mural thrombus.
Treatment of established arterial thrombosis includes the use of antiplatelet drugs and
thrombolytic therapy
Thrombolysis, also called fibrinolytic therapy, is the breakdown ( lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massiv ...
. Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.
*Aspirin and Triflusal irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA
2 (thromboxane - powerful vasoconstrictor that lowers cyclic AMP and initiates the platelet release reaction).
*Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI
2 – opposes actions of TXA
2
*Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex
*Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:
**Murine-human chimeric antibodies (e.g., abciximab)
**Synthetic peptides (e.g., eptifibatide)
**Synthetic non-peptides (e.g., tirofiban)
*Epoprostenol is a prostacyclin that is used to inhibit platelet aggregation during renal dialysis (with or without heparin) and is also used in primary pulmonary hypertension.
Management in the perioperative period
Antiplatlet therapy may increase the risk of a bleed during surgery, however, stopping therapy may increase the risk of other thrombotic problems including myocardial infarction.
When considering these medications and the risk-benefit ratio in the perioperative period, one must consider the risk of stopping the medication and a clot forming versus the risk of bleeding during or after the surgery if medication is continued. A 2018 Cochrane Review that included five randomized controlled trials found low-certainty evidence to suggest that continuing or discontinuing antiplatelet therapy for a non-cardiac surgery does not make a difference in mortality, major bleeds that require surgery, or ischaemic events.
The same review found moderate certainty evidence that continuing or discontinuing therapy also did not have a big difference on the incidence of bleeds requiring a blood transfusion.
* In patients with truly time-sensitive disease (defined in the 2014 ACC/AHA guidelines as needing to proceed in 2–6 weeks), DAPT can be stopped 3 (three) months (90 days) after a coronary stent is placed if postponing surgery any longer would result in significant morbidity. Examples of these types of surgeries include some cancer surgery and possibly some orthopedic surgery (non-urgent/emergent fracture management). Preferably 6 to 12 months of DAPT should be continued in patients having elective surgery.
* Bare metal stents required at least one month of DAPT
* Balloon angioplasty in the preoperative period——patients can proceed to surgery two weeks after the procedure.
* CABG: Patients may proceed with surgery as soon as they are healed from the coronary artery bypass procedure and they do not need any specific amount of time on DAPT
Dental management of patients on antiplatelet drugs
Dentists should be aware of the risk of prolonged bleeding time in patients taking antiplatelet drugs when planning dental treatments that are likely to cause bleeding. Therefore, it is important for dentists to know how to assess patient's bleeding risk and how to manage them.
Assess bleeding risk
Identify the likelihood and risk of dental treatment causing bleeding complications.
Drug toxicity
Antiplatelet drugs effect may be affected by patient's medications, current medical conditions, food and supplements taken. Antiplatelet drugs effect may be increased or decreased. An increase in antiplatelet effect would increase the risk of bleeding and could cause prolonged or excessive bleeding. A decrease in antiplatelet effect would reduce the risk of bleeding, but increase the thromboembolic risk.
Drug toxicity may increase when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients.
Medications
Medications that may increase antiplatelet drug effect:
* NSAIDS (e.g.: aspirin, ibuprofen, diclofenac, naproxen)
* Cytotoxic drugs or drugs associated with bone marrow suppression (e.g.: leflunomide, hydroxychloroquine, adalimumab, infliximab, etanercept, sulfasalazine, penicillamine, gold, methotrexate, azathioprine, mycophenolate)
* Other anticoagulants or antiplatelet drugs
* Drugs affecting the nervous system (e.g.:
Selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracell ...
s (SSRIs))
Medications that may decrease antiplatelet drug effect:
* Carbamazepine
* Erythromycin
* Fluconazole
* Omeprazole
Use of NSAIDs as part of dental management of patients with vascular disease should be discouraged as NSAIDs have antiplatelet effect. Instead, simple analgesics such as paracetamol or co-codamol should be of first choice. If NSAIDs are required, the risk of bleeding increases with duration of dental treatment.
Medical conditions
Medical conditions that may increase antiplatelet drugs' effect include:
Chronic
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
,
liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the sig ...
, haematological malignancy, recent or current
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, advanced heart failure, mild forms of inherited bleeding disorders (e.g.
haemophilia
Haemophilia, or hemophilia (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, ...
,
Von Willebrand's disease
Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ...
) and
idiopathic thrombocytopenic purpura
Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of oth ...
.
Food and supplements
Food and supplements that may increase antiplatelet drugs' effect:
St. John's wort, ginkgo biloba, garlic.
Oral antiplatelet drugs available in the UK
See also
*
Anticoagulant drug
*
Nitrophorin Nitrophorins are hemoproteins found in the saliva of blood-feeding insects. Saliva of the blood-sucking bug ''Rhodnius prolixus'' contains at least seven homologous nitrophorins, designated NP1 to NP7 in order of their relative abundance in the gla ...
*
Thrombolytic drug
Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...
References
{{Major Drug Groups
*