|
|
| Line 1: |
Line 1: |
| __NOTOC__
| |
| {{SI}}
| |
| {{CMG}}; {{AE}} {{JH}}
| |
|
| |
|
| ==Overview==
| |
|
| |
| '''Cangrelor''' is a [[P2Y12|P2Y<sub>12</sub>]] inhibitor under investigation as an [[antiplatelet drug]]<ref name="cat.sagepub.com">[http://cat.sagepub.com/cgi/content/abstract/15/2/177 Cangrelor Attenuates Coated-Platelet Formation]</ref> for [[intravenous]] application. Some P2Y<sub>12</sub> inhibitors are used clinically as effective inhibitors of [[adenosine diphosphate]]-mediated platelet activation and aggregation.<ref name="cat.sagepub.com"/> Unlike [[clopidogrel]] (Plavix), which is a [[prodrug]], cangrelor is an active drug not requiring [[metabolism|metabolic]] conversion.
| |
|
| |
| Poor interim results led to the abandonment of the two CHAMPION clinical trials in mid-2009.<ref>[http://www.medscape.com/viewarticle/702828 CHAMPION Trials With Cangrelor Stopped for Lack of Efficacy]</ref> The BRIDGE study, for short term use prior to surgery, continues.<ref>[http://seekingalpha.com/article/137521-what-cangrelor-failure-means-to-medicines What Cangrelor Failure Means to Medicines]</ref> The CHAMPION PHOENIX trial was a randomized study of over 11,000 patients published in 2013. It found usefulness of cangrelor in patients getting cardiac stents. Compared with [[clopidogrel]] given around the time of stenting, intravenous [[ADP]]-receptor blockade with cangrelor significantly reduced the rate of stent thrombosis and myocardial infarction.<ref>Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events (2013) Bhatt, DL etal. New England Journal of Medicine March 10, 2013 {{doi|10.1056/NEJMoa1300815}} (published initially online).</ref> Reviewers have questioned the methodology of the trial.<ref>{{cite journal | title = The Duel between Dual Antiplatelet Therapies | author = Lange, RA and Hillis, LD | journal = New England Journal of Medicine | date = March 10, 2013 | doi = 10.1056/NEJMe1302504}}</ref>
| |
|
| |
| ==Medical use==
| |
| According to recent phase 3 randomized trials, a cangrelor–[[clopidogrel]] combination is safe and has been found to be more effective than standard clopidogrel treatment at reducing [[ischemic]] events in the [[heart]], without increasing major [[bleeding]] in the treatment of stenotic [[coronary arteries]].<ref name= Kubica/> The advantages of this drug combination are most prominent in patients with [[myocardial infarction]].<ref name= Kubica >{{cite journal | author = Kubica, J. et al. | year = 2014 | title = Cangrelor: An Emerging Therapeutic Option for Patients with Coronary Artery Disease | journal = Curr Med Res Opin | pmid= 24393016}}</ref>
| |
|
| |
| Available [[antiplatelet]] drugs have delayed onset and offset of action.<ref name= Kubica/> Since cangrelor’s effects are immediate and quickly reversed, it is a more desirable drug for elective treatment of stenotic coronary arteries, high risk acute coronary syndromes treated with immediate coronary stenting, and for bridging those surgery patients who require P2Y12 inhibition.<ref name= Kubica/>
| |
|
| |
| Current evidence regarding cangrelor therapy is limited by the lack studies assessing cangrelor administration in conjunction with either [[prasugrel]] or [[ticagrelor]].<ref name= Kubica/>
| |
|
| |
| ==Pharmacology==
| |
| Cangrelor is a high-affinity, reversible inhibitor of P2Y12 receptors that causes almost complete inhibition of ADP-induced platelet aggregate.<ref name= Angiolillo >{{cite journal | author = Angiolillo, Dominick J., and Piera Capranzano | title = Pharmacology of Emerging Novel Platelet Inhibitors | title = American Heart Journal | volume = 156 | issue = 2 | year = 2008 | pages = 10S-5S}}</ref> It is a modified ATP derivative stable to enzymatic degradation.<ref name= Angiolillo/> It does not require metabolic conversion to an active metabolite . This allows cangrelor’s immediate effect after infusion,<ref name= Angiolillo/> and the therapeutic effects can be maintained with continuous infusion.<ref name= Bhatt >{{cite journal | author = Bhatt, et al. | year = 2013 | title = Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events | journal = New England Journal of Medicine | volume = 368 | pages = 1303-1313}}</ref> The pharmacokinetics of cangrelor has allow it to rapidly achieve steady-state concentrations with a clearance of 50 L/h and a half-life of 2.6 to 3.3 minutes. Cessation of its administration is associated with rapid removal, and normal [[platelet]] function is restored within 1 hour.<ref name= Bhatt/><ref name= Angiolillo/>
| |
|
| |
| ==Adverse effects==
| |
| Despite fewer bleeding events during cardiac surgery, cangrelor carries the risk of potential autoimmune reactions manifesting as dyspnea.<ref name= Serebruany >{{cite journal | author = Serebruany V.L. et al. | year = 2014 | title = Dyspnea and Reversibility of Antiplatelet Agents: Ticagrelor, Elinogrel, Cangrelor, and Beyond | journal = Cardiology | volume = 127| pages = 20-24}}</ref> Potential mechanisms for [[dyspnea]] following cangrelor treatment include: repeated binding and unbinding cycles, impaired [[platelet]] turnover, and lung sequestration or [[apoptosis]] of overloaded destructive [[platelets]].<ref name= Serebruany/> The dyspnea risks following cangrelor treatment, suggest a common mechanism linking transfusion-related acute lung injury, [[dyspnea]], and reversible [[platelet]] inhibition.<ref name= Serebruany/>
| |
|
| |
| The risk of [[dyspnea]] after intravenous cangrelor is smaller when compared with other reversible platelet P2Y12 receptor inhibitors, however, it is still significantly higher when compared to irreversible oral [[antiplatelet]] drugs or intravenous [[glycoprotein IIb/IIIa inhibitors]]; which do not increase the incidence of [[dyspnea]] at all.<ref name= Serebruany/>
| |
|
| |
| ==References==
| |
|
| |
| {{Reflist|2}}
| |
|
| |
| {{Antithrombotics}}
| |
|
| |
| [[Category:ADP receptor inhibitors]]
| |
| [[Category:Nucleotides]]
| |
| [[Category:Drugs]]
| |