Cangrelor: Difference between revisions
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
{{SI}} | {{SI}} | ||
{{CMG}}; {{AE}} {{JH}} | {{CMG}}; {{AE}} {{JH}} | ||
==Overview== | ==Overview== | ||
| Line 50: | Line 7: | ||
'''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. | '''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> | 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== | ==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 | 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/> | 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/> | 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== | ==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/> | 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== | ==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/> | 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/> | 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== | ==References== | ||
Revision as of 19:18, 9 July 2014
|
WikiDoc Resources for Cangrelor |
|
Articles |
|---|
|
Most recent articles on Cangrelor |
|
Media |
|
Evidence Based Medicine |
|
Clinical Trials |
|
Ongoing Trials on Cangrelor at Clinical Trials.gov Clinical Trials on Cangrelor at Google
|
|
Guidelines / Policies / Govt |
|
US National Guidelines Clearinghouse on Cangrelor
|
|
Books |
|
News |
|
Commentary |
|
Definitions |
|
Patient Resources / Community |
|
Patient resources on Cangrelor Discussion groups on Cangrelor Directions to Hospitals Treating Cangrelor Risk calculators and risk factors for Cangrelor
|
|
Healthcare Provider Resources |
|
Causes & Risk Factors for Cangrelor |
|
Continuing Medical Education (CME) |
|
International |
|
|
|
Business |
|
Experimental / Informatics |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jesus Rosario Hernandez, M.D. [2]
Overview
Cangrelor is a P2Y12 inhibitor under investigation as an antiplatelet drug[1] for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation.[1] Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion.
Poor interim results led to the abandonment of the two CHAMPION clinical trials in mid-2009.[2] The BRIDGE study, for short term use prior to surgery, continues.[3] 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.[4] Reviewers have questioned the methodology of the trial.[5]
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.[6] The advantages of this drug combination are most prominent in patients with myocardial infarction.[6]
Available antiplatelet drugs have delayed onset and offset of action.[6] 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.[6]
Current evidence regarding cangrelor therapy is limited by the lack studies assessing cangrelor administration in conjunction with either prasugrel or ticagrelor.[6]
Pharmacology
Cangrelor is a high-affinity, reversible inhibitor of P2Y12 receptors that causes almost complete inhibition of ADP-induced platelet aggregate.[7] It is a modified ATP derivative stable to enzymatic degradation.[7] It does not require metabolic conversion to an active metabolite . This allows cangrelor’s immediate effect after infusion,[7] and the therapeutic effects can be maintained with continuous infusion.[8] 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.[8][7]
Adverse effects
Despite fewer bleeding events during cardiac surgery, cangrelor carries the risk of potential autoimmune reactions manifesting as dyspnea.[9] 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.[9] The dyspnea risks following cangrelor treatment, suggest a common mechanism linking transfusion-related acute lung injury, dyspnea, and reversible platelet inhibition.[9]
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.[9]
References
- ↑ 1.0 1.1 Cangrelor Attenuates Coated-Platelet Formation
- ↑ CHAMPION Trials With Cangrelor Stopped for Lack of Efficacy
- ↑ What Cangrelor Failure Means to Medicines
- ↑ 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).
- ↑ Lange, RA and Hillis, LD (March 10, 2013). "The Duel between Dual Antiplatelet Therapies". New England Journal of Medicine. doi:10.1056/NEJMe1302504.
- ↑ 6.0 6.1 6.2 6.3 6.4 Kubica, J.; et al. (2014). "Cangrelor: An Emerging Therapeutic Option for Patients with Coronary Artery Disease". Curr Med Res Opin. PMID 24393016.
- ↑ 7.0 7.1 7.2 7.3 Angiolillo, Dominick J., and Piera Capranzano (2008). "American Heart Journal". 156 (2): 10S–5S.
- ↑ 8.0 8.1 Bhatt; et al. (2013). "Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events". New England Journal of Medicine. 368: 1303–1313.
- ↑ 9.0 9.1 9.2 9.3 Serebruany V.L.; et al. (2014). "Dyspnea and Reversibility of Antiplatelet Agents: Ticagrelor, Elinogrel, Cangrelor, and Beyond". Cardiology. 127: 20–24.