Antiplatelet drug
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of
Antiplatelet drugs are widely used in primary and secondary prevention of thrombotic disease, especially myocardial infarction and ischemic stroke.[1]
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. 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.[3]
Choice
Antiplatelet medications are one of the primary recommendations for treatment of both stable
Dual antiplatelet therapy
Often a combination of aspirin plus an
Classification
Classes of antiplatelet drugs include:
- Adenosine diphosphate (ADP) receptor inhibitors
- Cangrelor (Kengreal)
- Clopidogrel (Plavix)
- Prasugrel (Effient)
- Ticagrelor (Brilinta)
- Ticlopidine (Ticlid)
- Adenosine reuptake inhibitors
- Dipyridamole (Persantine)
- Glycoprotein IIB/IIIA inhibitors(intravenous use only)
- Abciximab (ReoPro)
- Eptifibatide (Integrilin)
- Tirofiban (Aggrastat)
- Irreversible cyclooxygenase inhibitors
- Phosphodiesterase inhibitors
- Cilostazol (Pletaal)
- protease-activated receptor 1a.k.a. PAR-1)
- Vorapaxar (Zontivity)
- Thromboxane inhibitors
- Thromboxane receptor antagonists
- Thromboxane synthase inhibitors
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.[3] 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.[3]
Treatment of established arterial thrombosis includes the use of antiplatelet drugs and
- Aspirin and Triflusal irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA2 (thromboxane – powerful vasoconstrictor that lowers cyclic AMP and initiates the platelet release reaction).
- Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex
- Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI2 – opposes actions of TXA2
- 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.
- 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 non-peptides (e.g., tirofiban)
- Synthetic peptides (e.g., eptifibatide)
Management in the perioperative period
Antiplatelet therapy may increase the risk of a bleed during surgery, however, stopping therapy may increase the risk of other thrombotic problems including myocardial infarction.[9] 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.[10] 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.[9] 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.[9]
- Balloon angioplasty in the preoperative period——patients can proceed to surgery two weeks after the procedure.
- Bare metal stents required at least one month of DAPT
- 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
- 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.
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.[3]
Assess bleeding risk
Identify the likelihood and risk of dental treatment causing bleeding complications.[3]
Dental procedures unlikely to cause bleeding | Dental procedures with low risk of post-operative bleeding complications | Dental procedures with high risk of post-operative bleeding complications |
Local anaesthesia using aspirating syringe and vasoconstrictor | Simple extractions up to 3 teeth with restricted wound size | Extractions involving surgery, large wound or more than 3 teeth at once |
Basic Periodontal examination (BPE) | Incision and drainage of intra-oral swellings | Flap raising procedures |
Supragingival plaque, calculus, stain removal | Six point full periodontal examination | Gingival recontouring |
Direct or indirect restoration with supragingival margins | Root surface debridement and subgingival scaling | Biopsies |
Orthograde endodontics | Direct or indirect restorations with subgingival margins | |
Prosthetic procedures | ||
Fitting and adjustment of orthodontic appliances. |
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.[3] Drug toxicity may increase when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients.[11]
Medications
Medications that may increase antiplatelet drug effect:[3]
- Cytotoxic drugs or drugs associated with bone marrow suppression (e.g.: leflunomide, hydroxychloroquine, adalimumab, infliximab, etanercept, sulfasalazine, penicillamine, gold, methotrexate, azathioprine, mycophenolate)
- Drugs affecting the nervous system (e.g.: Selective serotonin reuptake inhibitors (SSRIs))
- NSAIDS (e.g.: aspirin, ibuprofen, diclofenac, naproxen)
- Other anticoagulants or antiplatelet drugs
Medications that may decrease antiplatelet drug effect:[3]
- 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.[3]
Medical conditions
Medical conditions that may increase antiplatelet drugs' effect include:[3]
Chronic
Food and supplements
Food and supplements that may increase antiplatelet drugs' effect:[3]
St. John's wort, ginkgo biloba, garlic.
Oral antiplatelet drugs available in the UK
Oral Antiplatelet Drugs | UK Trade Name | Other Names (Non-UK) |
Aspirin | Nu-Seals, Microprin, caprin Dual with dipyridamole: Asasantin Retard, Molita Modified Release | acetylsalicylic acid - There are numerous brand names for Aspirin |
Clopidogrel | Plavix, Grepid | Iscover |
Dipyridamole | Persantin, Persantin Retard, Attia Modified Release, Ofcram PR. Dual with aspirin: Asasantin Retard, Molita Modified Release | |
Prasugrel | Efient | Effient, Prasita |
Ticagrelor | Brilique | Brilinta, Possia |
See also
- Anticoagulant drug
- Nitrophorin
- Thrombolytic drug
References
- ^ PMID 16402110.
- S2CID 210149420.
- ^ a b c d e f g h i j k l "SDCEP Anticoagulants and Antiplatelets" (PDF). Archived from the original (PDF) on 2017-03-28. Retrieved 2016-03-09.
- ^ PMID 23166211.
- ^ PMID 21450428.
- S2CID 207592252.
- PMID 23473370.
- PMID 26324537.
- ^ PMID 30019463.
- PMID 29767644.
- PMID 21098354.