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Anti-platelet therapy in acute coronary syndrome
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
Kunal Mahajan, Yashasvi Rajeev, K Sarat Chandra
It belongs to a new class of drugs termed as non-thienopyridine adenosine triphosphate analogues. It is an intravenous and competitive P2Y12 inhibitor and has a reversible mode of action. It has a short half-life of 5 minutes only. Cangrelor has a very rapid onset and offset of action, unlike the currently approved oral P2Y12 anti-platelet agents, which require hours to be effective. Furthermore, cangrelor does not require in vivo bioactivation. It, therefore, reaches a steady-state in plasma within a few minutes of its administration and achieves more than 90% inhibition of platelet activation resulting from the P2Y12 pathway [2,3]. Multiple randomised controlled trials, comparing the use of cangrelor with the current standard therapy, have found no significant differences in the mortality or further MI when patients were treated with either cangrelor or clopidogrel before [27] or during PCI [28]. However, in a double-blind placebo-controlled randomised trial involving 11,145 patients, cangrelor led to a significant reduction in the rate of ischaemic events during PCI, compared with clopidogrel, without any increase in severe bleeding [29]. Cangrelor was subsequently approved by US and European regulatory agencies in 2015 for use in patients undergoing PCI. It is particularly useful in patients with ACS who are unable to take oral agents due to repeated vomiting or those in a state of shock or on a ventilator. It is also very useful in patients with ACS who require urgent surgery, as its use avoids preloading with DAPT and thus permits early surgery without waiting 5–7 days for oral drug washout.
Antiplatelet therapy in interventional cardiology
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
Bleeding is the most common adverse reaction with this drug class. Bleeding is increased with ticagrelor and cangrelor compared to clopidogrel. In the Platelet Inhibition and Patient Outcomes (PLATO) trial there was a higher rate of non-coronary bypass-related major bleeding (4.5% vs. 3.8%, P = 0.03) and the TIMI criteria (2.8% vs. 2.2%, P = 0.03).35 In addition, there were increased episodes of intracranial bleeding with ticagrelor (0.3% vs. 0.2%, P = 0.06), including fatal intracranial bleeding (0.1% vs. 0.01%, P = 0.02).35
Therapy of acute myocardial infarction
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Joshua M. Stolker, Michael W. Rich
One concern with any of the oral antiplatelet agents is reduced gastrointestinal absorption during ACS and the potential for higher rates of stent thrombosis or other thrombotic complications, particularly among patients receiving morphine or other opioids for treatment of pain (41). In addition, patients loaded with oral antiplatelet therapy experience higher rates of perioperative bleeding if urgent CABG is needed after cardiac catheterization, so many physicians avoid loading oral antiplatelet therapy until after coronary angiography has been performed to avoid the 5- to 7-day delay required if CABG is needed. Cangrelor is an intravenous P2Y12 inhibitor that reduced periprocedural complications during PCI (particularly stent thrombosis) when compared with clopidogrel in a clinical trial (42), with similar benefits in the subgroups of patients <75 and >75 years of age. This drug has not been compared to the newer, more potent oral antiplatelet agents (prasugrel, ticagrelor), and its higher cost has likely contributed to its relatively restricted use thus far in the United States.
Tackling the gap in platelet inhibition with oral antiplatelet agents in high-risk patients undergoing percutaneous coronary intervention
Published in Expert Review of Cardiovascular Therapy, 2021
Piera Capranzano, Dominick J. Angiolillo
Among the P2Y12 inhibitors, cangrelor is the only intravenous agent currently available in clinical practice. It is approved for use in patients who are P2Y12 receptor naïve who are undergoing PCI during which it is administered as a bolus followed by a continuous infusion for at least 2 h or for the duration of the procedure, whichever is longer. Cangrelor is a potent direct-acting reversible P2Y12 antagonist providing an immediate (≈2 min) onset of action and a very short offset with a rapid (≈60 minutes) restoration of platelet function after its discontinuation [71]. It has been shown that cangrelor reaches high levels of platelet inhibition (>95%) and provide further decrease in platelet aggregation in patients treated with the more potent oral P2Y12 inhibitors [71–74].
Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction
Published in Expert Opinion on Pharmacotherapy, 2020
Amit Rout, Udaya S Tantry, Marko Novakovic, Ajaypaul Sukhi, Paul A Gurbel
Cangrelor is a potent, intravenously administered, direct-acting P2Y12 antagonist with a potent antiplatelet effect, rapid onset and quick, reversible action. A cardioprotective effect of cangrelor beyond potent inhibition of platelets was demonstrated in two animal studies. Administration of cangrelor shortly before IRI in rabbits reduced infarct size by approximately 30%, and this effect was dose-dependent and correlated with platelet inhibition. However, delaying the cangrelor administration by 10 minutes after the onset of reperfusion eliminated the cardioprotective effect [74]. In a primate model, cangrelor started just prior to reperfusion, and ischemic preconditioning significantly decreased infarct to the same extent [75]. Sphingosine kinase activity is suggested as one of the pathways of cardioprotection by cangrelor [76].
P2Y12 inhibitors for the treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention: current understanding and outcomes
Published in Expert Review of Cardiovascular Therapy, 2019
Dimitrios Alexopoulos, Charalampos Varlamos, Aikaterini Mpahara, Ioannis Lianos
Cangrelor use in every day clinical practice is increasing with the most extensive experience so far presented within the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) [60]. In the last 2 years, 915 patients with ACS were treated with cangrelor, 899 of them (98.25%) were STEMI patients and 273 (19%) who had suffered cardiac arrest. One third of patients had received pretreatment with ticagrelor and another one third received ticagrelor during cangrelor infusion. As a control group served 4,614 STEMI identified during the same period. Cangrelor was administered more frequently in patients with high ischemic burden, such as patients undergoing thrombus aspiration or left main PCI. Despite being used in more high-risk patients, stent thrombosis rates were low and similar between cangrelor-treated and non-cangrelor-treated patients.