Cangrelor fails to show benefit in Phase III trials

Cangrelor fails to show benefit in Phase III trialsCangrelor, a novel anti-platelet agent, is an intravenously administered P2Y12 antagonist with an almost instantaneous onset of action that produces profound and stable platelet inhibition in over 95% of individuals. Furthermore, the effect of the drug is quickly reversible and platelet responses approach baseline within 60 minutes of discontinuation of infusion. Two large phase III trials (CHAMPION – Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) examined the effect of cangrelor; however, both were stopped prematurely after an interim analysis suggested a lack of benefit. 
In the first of these (CHAMPION-PCI), 8716 patients undergoing PCI following an acute coronary syndrome, were studied in a double blind double-placebo controlled trial of either 600mg clopidogrel or cangrelor bolus and infusion started prior to PCI. The study failed to show any superiority of cangrelor in its primary end-point of death, myocardial infarction or revascularisation at both 48 hours and 30 days. Added to this, major bleeding was increased with cangrelor although this did not quite meet statistical significance (p=0.06). Similarly in the CHAMPION-PLATFORM trial, where cangrelor was trialled against placebo in 5362 patients, with all patients receiving clopidogrel after the end of the procedure (a practice which allows patients to proceed to surgery if needed), cangrelor again failed to show any benefit in the same primary end-point at 48 hours or 30 days and again showed increased bleeding. Cangrelor did, however, show greater platelet inhibition than clopidogrel. The reasons why this did not translate into improved clinical outcomes are not immediately clear.
In two large phase III trials the novel IV anti-platelet agent cangrelor failed to show parity with treatment with clopidogrel in acute coronary syndrome patients undergoing PCI. With several other anti-platelet agents recently showing promise, it remains to be seen whether any role remains for cangrelor.

Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, Pollack CV Jr, Montalescot G, Mahaffey KW, Kleiman NS, Goodman SG, Amine M, Angiolillo DJ, Becker RC, Chew DP, French WJ, Leisch F, Parikh KH, Skerjanec S and Bhatt DL. Platelet Inhibition with Cangrelor in Patients Undergoing PCI.. N Engl J Med. 2009 361:2318-2329

Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, Kleiman NS, Goodman SG, White HD, Mahaffey KW, Pollack CV Jr, Manoukian SV, Widimsky P, Chew DP, Cura F, Manukov I, Tousek F, Jafar MZ, Arneja J, Skerjanec S and Harrington RA. Intravenous Platelet Blockade with Cangrelor during PCI N Engl J Med. 2009 361:2330-2341
• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57.

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