Antiplatelet agent - cangrelor tetrasodium
Platelets play a key role in clot production, as they are involved in early-stage atherosclerosis development and in acute ischaemic events.
Platelets play a key role in clot production, as they are involved in early-stage atherosclerosis development and in acute ischaemic events.
One of the factors involved in thrombus formation is the adhesion of platelets to cell walls. Platelets have receptors for adenosine diphosphate on their membrane surface, and their storage granules contain ADP which is released during platelet secretion. This is one of the factors involved in the regulation of platelet responses. ADP is an agonist for and ATP, a competitive antagonist for the platelet specific ADP receptor P2Y12, which potentiates platelet dense granule release. Cangrelor, being developed by The Medicines Company, is an ATP analogue that acts at this receptor.
In one randomised, placebo-controlled Phase II trial in 399 patients undergoing percutaneous coronary intervention, 200 were given placebo or a 1, 2 or 4µg/kg/min infusion of cangrelor on top of aspirin and heparin prior to surgery.1 The rest had the highest dose of cangrelor or abciximab. The combined rate of major or minor bleeding was 13% in the first cangrelor group compared with 8% of the placebo group, and 7% compared with 10% for abciximab in the second; none of these differences were statistically significant. Similar cardiac event rates were seen for cangrelor and abciximab. Platelet aggregation returned to baseline more quickly with cangrelor than abciximab.
In another trial, patients with unstable angina pectoris or non-Q wave myocardial infarction were randomised to a 72-hour infusion of cangrelor or placebo alongside aspirin and heparin.2 No serious bleeding events were seen, although minor bleeding was slightly higher with cangrelor. It has been investigated alongside clopidogrel.
Ten healthy volunteers were given a 600mg loading dose of clopidogrel and their platelet function monitored for six hours.3 Two weeks on, a similar dose was given with cangrelor as a 30µg/kg intravenous bolus followed by a two-hour infusion at 4µg/kg/min. Another 10 volunteers were given the clopidogrel dose after the cangrelor bolus and a one-hour infusion. The sustained platelet inhibition expected with clopidogrel did not happen when the two doses were given together, but did when given sequentially.
Phase III trials are underway.