Editing Antiplatelet drug

{{Short description|Class of pharmaceuticals}}
An '''antiplatelet drug''' (antiaggregant), also known as a '''platelet agglutination inhibitor''' or '''platelet aggregation inhibitor''', is a member of a class of [[pharmacology|pharmaceuticals]] that decrease [[platelet aggregation]]<ref name=":2">{{cite journal | vauthors = Born G, Patrono C | title = Antiplatelet drugs | journal = British Journal of Pharmacology | volume = 147 Suppl 1 | issue = Suppl 1 | pages = S241–S251 | date = January 2006 | pmid = 16402110 | pmc = 1760725 | doi = 10.1038/sj.bjp.0706401 }}</ref> and inhibit [[thrombus]] formation. They are effective in the [[Artery|arterial]] circulation where classical [[Vitamin K antagonist]] [[anticoagulant]]s have minimal effect.<ref>{{cite journal | vauthors = García-Ropero Á, Vargas-Delgado AP, Santos-Gallego CG, Badimon JJ | title = Direct Oral Anticoagulants and Coronary Artery Disease: The Debacle of the Aspirin Era? | journal = Journal of Cardiovascular Pharmacology | volume = 75 | issue = 4 | pages = 269–275 | date = April 2020 | pmid = 31923049 | doi = 10.1097/FJC.0000000000000795 | s2cid = 210149420 }}</ref>
      
Antiplatelet drugs are widely used in primary and secondary prevention of thrombotic disease, especially [[myocardial infarction]] and [[Stroke|ischemic stroke]].<ref name=":2" />

'''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.<ref name=":0">{{Cite web |title=SDCEP Anticoagulants and Antiplatelets |url=http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf |access-date=2016-03-09 |archive-date=2017-03-28 |archive-url=https://web.archive.org/web/20170328223906/http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf |url-status=dead }}</ref>

==Choice==
Antiplatelet medications are one of the primary recommendations for treatment of both stable<ref name=":3">{{cite journal | vauthors = Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB, Kligfield PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ, Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR, Smith SC, Spertus JA, Williams SV, Anderson JL | display-authors = 6 | title = 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart diseasem | collaboration = American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons | journal = Circulation | volume = 126 | issue = 25 | pages = e354–e471 | date = December 2012 | pmid = 23166211 | doi = 10.1161/CIR.0b013e318277d6a0 | doi-access = free }}</ref> and unstable<ref name=":4">{{cite journal | vauthors = Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE, Ettinger SM, Fesmire FM, Ganiats TG, Jneid H, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP, Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE, Chavey WE, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS | display-authors = 6 | title = 2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline) | collaboration = American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons | journal = Journal of the American College of Cardiology | volume = 57 | issue = 19 | pages = 1920–1959 | date = May 2011 | pmid = 21450428 | doi = 10.1016/j.jacc.2011.02.009 | doi-access = free }}</ref> [[Coronary artery disease|ischemic heart disease]]. Most commonly, [[aspirin]] is used as a single medication in cases of uncomplicated [[stable angina]], and in some cases of [[unstable angina]]. If a patient [[Salicylate sensitivity|does not tolerate aspirin]], ADP/P2Y inhibitors may be used as single-drug therapy instead. More severe and complicated cases are treated with dual antiplatelet therapy, or in some cases triple therapy that includes [[direct oral anticoagulants]].<ref>{{cite journal | vauthors = Gurbel PA, Fox KA, Tantry US, Ten Cate H, Weitz JI | title = Combination Antiplatelet and Oral Anticoagulant Therapy in Patients With Coronary and Peripheral Artery Disease | journal = Circulation | volume = 139 | issue = 18 | pages = 2170–2185 | date = April 2019 | pmid = 31034291 | doi = 10.1161/CIRCULATIONAHA.118.033580 | s2cid = 207592252 | doi-access = free }}</ref> Clinicians must make a choice that balances patient risk with the increased risks of bleeding associated with combination therapy.<ref name=":3" /><ref name=":4" />

==Dual antiplatelet therapy==
Often a combination of aspirin plus an [[P2Y receptor|ADP/P2Y]] inhibitor<ref name="pmid_23473370">{{Citation |last1=Lange |first1=RA |last2=Hillis |first2=LD |year=2013 |title=The duel between dual antiplatelet therapies |journal=N Engl J Med |volume=368 |issue=14 |pages=1356–1357 |pmid=23473370 |doi=10.1056/NEJMe1302504 |postscript=.}}</ref> (such as [[clopidogrel]], [[prasugrel]], [[ticagrelor]], or another) is used to obtain greater effectiveness than with either agent alone. This is known as "dual antiplatelet therapy" (or '''DAPT'''). DAPT is used in patients who have, or are at high risk of developing, unstable angina, [[NSTEMI]] myocardial infarctions, and other high-risk thrombotic conditions.<ref name=":4" /> Dual antiplatelet therapy has been found to significantly reduce rates of heart attacks, [[stroke]]s, and overall cardiovascular death, but is not used in low-risk patients because it significantly increases the risks of [[Bleeding|major bleeding]].<ref>{{cite journal | vauthors = Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L, Valgimigli M, Park SJ, Montalescot G, Sabatine MS, Braunwald E, Bhatt DL | display-authors = 6 | title = Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials | journal = European Heart Journal | volume = 37 | issue = 4 | pages = 390–399 | date = January 2016 | pmid = 26324537 | doi = 10.1093/eurheartj/ehv443 | doi-access = free }}</ref>

==Classification==
Classes of antiplatelet drugs include:
*[[Adenosine diphosphate (ADP) receptor inhibitor]]s
**[[Cangrelor]] (Kengreal)
**[[Clopidogrel]] (Plavix)
**[[Prasugrel]] (Effient)
**[[Ticagrelor]] (Brilinta)
**[[Ticlopidine]] (Ticlid)
*[[Adenosine reuptake inhibitor]]s
**[[Dipyridamole]] (Persantine)
*[[Glycoprotein IIB/IIIA inhibitor]]s (intravenous use only)
**[[Abciximab]] (ReoPro)
**[[Eptifibatide]] (Integrilin)
**[[Tirofiban]] (Aggrastat)
*Irreversible [[cyclooxygenase]] inhibitors
** [[Aspirin]]
** [[Triflusal]] (Disgren)
*[[Phosphodiesterase inhibitor]]s
**[[Cilostazol]] (Pletaal)
*[[Protease-activated receptor-1 antagonist]]s (which inhibit the [[protease-activated receptor 1]] {{aka}} PAR-1)
**[[Vorapaxar]] (Zontivity)
*[[Thromboxane inhibitor]]s
**[[Thromboxane receptor antagonist]]s
***[[Terutroban]]
**[[Thromboxane synthase inhibitors]]

==Usage==

<!-- This study is so narrow in focus that it can hardly be used to demonstrate across-the-board evidence.  Although I cannot understand Romanian (the language in which the paper is written), a single study with a small population of 25 patients using different types of antiplatelet drugs were subjected to implant surgery in which primary collagen plugs and Vicryl sutures were used, presumably to obtain primary closure when possible, demonstrated no bleeding complications.  However, various types of procedures were done (18 extractions, 6 sinus augmentations, etc.) to preclude a true comparison among surgeries and the ability to generalize to other cases.

=== In dental implantation procedures ===
Dental implant procedures can be safely performed in patients on long-term antiplatelet medication, with no interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.<ref name="RevistaOMF">
{{cite journal 
 |author= Mihai Bogdan Bucur 
 |author-link= Mihai Bogdan Bucur 
 |title= Antiplatelet treatment implications in oral implantology
 |language= ro
 |journal= [[Revista de chirurgie oro-maxilo-facială și implantologie|Rev. chir. oro-maxilo-fac. implantol.]]
 |issn= 2069-3850
 |volume= 2
 |issue= 3
 |pages= 6–9
 |date=Nov 2011
 |url= http://www.revistaomf.ro/(39)
 |id= 39
 |access-date= 2012-04-15 }}(webpage has a translation button)
</ref> -->=== 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.<ref name=":0" /> 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.<ref name=":0" />

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 TXA<sub>2</sub> (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 PGI<sub>2</sub> – opposes actions of TXA<sub>2</sub>
*'''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.<ref name=":1">{{cite journal | vauthors = Lewis SR, Pritchard MW, Schofield-Robinson OJ, Alderson P, Smith AF | title = Continuation versus discontinuation of antiplatelet therapy for bleeding and ischaemic events in adults undergoing non-cardiac surgery | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD012584 | date = July 2018 | pmid = 30019463 | pmc = 6513221 | doi = 10.1002/14651858.CD012584.pub2 }}</ref> 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.<ref>{{cite journal | vauthors = Yeung LY, Sarani B, Weinberg JA, McBeth PB, May AK | title = Surgeon's guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation | journal = Trauma Surgery & Acute Care Open | volume = 1 | issue = 1 | pages = e000022 | date = 2016 | pmid = 29767644 | pmc = 5891708 | doi = 10.1136/tsaco-2016-000022 }}</ref> 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.<ref name=":1" /> 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.<ref name=":1" />

* 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.<ref name=":0" />

=== Assess bleeding risk ===
Identify the likelihood and risk of dental treatment causing bleeding complications.<ref name=":0" />
{| class="wikitable"
! 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.<ref name=":0" /> Drug toxicity may increase when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients.<ref>{{cite journal | vauthors = Shehab N, Sperling LS, Kegler SR, Budnitz DS | title = National estimates of emergency department visits for hemorrhage-related adverse events from clopidogrel plus aspirin and from warfarin | journal = Archives of Internal Medicine | volume = 170 | issue = 21 | pages = 1926–1933 | date = November 2010 | pmid = 21098354 | doi = 10.1001/archinternmed.2010.407 | doi-access = free }}</ref>

=== Medications ===
Medications that may increase antiplatelet drug effect:<ref name=":0" />
* 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 inhibitor]]s (SSRIs))
* NSAIDS (e.g.: aspirin, ibuprofen, diclofenac, naproxen)
* Other anticoagulants or antiplatelet drugs
Medications that may decrease antiplatelet drug effect:<ref name=":0" />
* 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.<ref name=":0" />

=== Medical conditions ===
Medical conditions that may increase antiplatelet drugs' effect include:<ref name=":0" />

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:<ref name=":0" />

St. John's wort, ginkgo biloba, garlic.

== Oral antiplatelet drugs available in the UK ==
{| class="wikitable"
! 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
|}
<ref name=":0" />

== See also ==
*[[Anticoagulant drug]]
*[[Nitrophorin]]
*[[Thrombolytic drug]]

== References ==
{{Reflist}}

{{Antithrombotics}}
{{Major Drug Groups}}

[[Category:Antiplatelet drugs|*]]