REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. This trial tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention (PCI), followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding.
A commentary notes that in view of the excess of bleeding events with REG1, despite availability of a reversal agent, and no reduction in hard ischaemic endpoints in more than 3000 patients, it is doubtful whether this approach to factor IXa blockade will go into further clinical development. However the commentators believe it is too early to halt investigation of factor IXa blockade in PCI and suggests the combination of a novel anticoagulant with a specific reversal molecule should be tested in more trials, but caution that pegylated agents seem to be hazardous in patients with acute coronary syndromes, therefore, a new formulation of the factor IXa inhibitor without pegylation would be welcome- but the agent—which in the current trial was given as bolus (similar to the antidote)—would then be infused continuously in the same way as bivalirudin or heparin, which is a practical disadvantage.