Antiplatelet drug

An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation[1] and inhibit thrombus formation. They are effective in the arterial circulation where anticoagulants 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.[2] 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.[2]

Choice

A 2006 review[3] states: "...low-dose aspirin increases the risk of major bleeding 2-fold compared with placebo. 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[4] (such as clopidogrel, prasugrel, ticagrelor, 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 inhibitors
  • Adenosine diphosphate (ADP) receptor inhibitors
    • Cangrelor (Kengreal)
    • Clopidogrel (Plavix)
    • Prasugrel (Effient)
    • Ticagrelor (Brilinta)
    • Ticlopidine (Ticlid)
  • Phosphodiesterase inhibitors
    • Cilostazol (Pletaal)
  • Protease-activated receptor-1 (PAR-1) antagonists
    • Vorapaxar (Zontivity)
  • Glycoprotein IIB/IIIA inhibitors (intravenous use only)
    • Abciximab (ReoPro)
    • Eptifibatide (Integrilin)
    • Tirofiban (Aggrastat)
  • Adenosine reuptake inhibitors
    • Dipyridamole (Persantine)
  • Thromboxane inhibitors
    • Thromboxane synthase inhibitors
    • Thromboxane receptor antagonists
      • Terutroban

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.[2] 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.[2]

Treatment of established arterial thrombosis includes the use of antiplatelet drugs and thrombolytic therapy. 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 TXA2 (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 PGI2 – opposes actions of TXA2
  • 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.[5] 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.[6] 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.[5] The same review found that continuing or discontinuing therapy also did not have a big difference on the incidence of bleeds requiring a blood transfusion (moderate certainty evidence).[5]

  • In patients with truly time-sensitive diseases (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.[2]

Assess bleeding risk

Identify the likelihood and risk of dental treatment causing bleeding complications.[2]

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 results in prolonged or excessive bleeding. A decrease in antiplatelet effect would reduce the risk of bleeding and potentially increase the thromboembolic risk.[2] Drug toxicity also may increased when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients.[7]

Medications

Medications that may increase antiplatelet drugs effect:[2]

  • NSAIDS (e.g.: aspirin, ibuprofen, diclofenac, naproxen)
  • Cytotoxic drugs or drugs associated with bone marrow suppression (e.g.: leflunamide, 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 inhibitors (SSRIs))

Medications that may decrease antiplatelet drugs effect:[2]

  • Carbamazepine
  • Erythromycin
  • Fluconazole
  • Omeprazole

Usage of NSAIDS as part of dental management of patients with vascular disease should be discouraged as NSAIDS has antiplatelet effect. Instead, simple analgesics such as paracetamol, co-codamol should be of first choice. If NSAIDS is required, dentist should be aware of the risk of bleeding and minimise treatment length.[2]

Medical conditions

Medical conditions that may increase antiplatelet drugs effect:[2]

Chronic kidney failure, liver disease, haematological malignancy, recent or current chemotherapy, advanced heart failure, mild forms of inherited bleeding disorders (e.g. haemophilia, Von Willebrand's disease) and idiopathic thrombocytopenic purpura.

Food and supplements

Food and supplements that may increase antiplatelet drugs' effect:[2]

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 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

[2]

See also

References
  1. "agents.htm {{{2}}}" at Dorland's Medical Dictionary
  2. "SDCEP Anticoagulants and Antiplatelets" (PDF).
  3. The American Journal of Medicine, Volume 119, Issue 8, Pages 624-638, August 2006: Systematic Review and Meta-analysis of Adverse Events of Low-dose Aspirin and Clopidogrel in Randomized Controlled Trials Retrieved 2013-02-08
  4. Lange, RA; Hillis, LD (2013), "The duel between dual antiplatelet therapies", N Engl J Med, 368 (14): 1356–1357, doi:10.1056/NEJMe1302504, PMID 23473370.
  5. Lewis, Sharon R.; Pritchard, Michael W.; Schofield-Robinson, Oliver J.; Alderson, Phil; Smith, Andrew F. (2018-07-18). "Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery". The Cochrane Database of Systematic Reviews. 7 (10): CD012584. doi:10.1002/14651858.CD012584.pub2. ISSN 1469-493X. PMC 6513221. PMID 30019463.
  6. Yeung, Louise Y. Y.; Sarani, Babak; Weinberg, Jordan A.; McBeth, Paul B.; May, Addison K. (2016). "Surgeon's guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation". Trauma Surgery & Acute Care Open. 1 (1): e000022. doi:10.1136/tsaco-2016-000022. ISSN 2397-5776. PMC 5891708. PMID 29767644.
  7. Shehab, Nadine; Laurence S. Sperling; Scott R. Kegler; Daniel S. Budnitz (2010-11-22). "National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin". Arch Intern Med. 170 (21): 1926–1933. doi:10.1001/archinternmed.2010.407. PMID 21098354. Retrieved 2010-11-23.
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