Updated November 13, 2011 (Orlando, Florida) — The ISAR-REACT-4 trial has shown that bivalirudin is preferable to abciximab plus heparin in NSTEMI patients undergoing PCI [1].
In the trial, presented today at the American Heart Association 2011 Scientific Sessions and simultaneously published online in the New England Journal of Medicine, the primary end point was not significantly different between the two groups, but bivalirudin was associated with less bleeding.
Lead investigator Dr Adnan Kastrati (Deutsches Herzzentrum, Technische Universität, Munich, Germany) explained to heartwire that the ACUITY trial has already suggested that bivalirudin may be preferable to a GP IIb/IIIa blocker plus heparin in these patients, but he pointed out that ACUITY was a very heterogeneous trial, "so it is difficult to know for sure which patient groups benefited from bivalirudin." He noted that only 50% of the ACUITY patients had raised troponins (so were classed as NSTEMI patients). In addition, 10% had CABG and 30% had no intervention, so only 60% actually underwent PCI. And there was a mixture of heparin and low-molecular-weight heparin used, and any one of the three GP IIb/IIIa blockers could be used. "So it was just too heterogeneous to give concrete answers for individual patient groups."
He said his group conducted the ISAR-REACT-4 trial because they believed that abciximab would be better than bivalirudin in the NSTEMI population. This belief was based on the result of the ISAR-REACT-2 trial, which showed a 25% reduction in events with abciximab vs heparin in a similar population. "But we were proved wrong," he added.
In the ISAR-REACT-4 trial, 1721 NSTEMI patients were randomized to abciximab plus unfractionated heparin or bivalirudin immediately before PCI.
Results showed that abciximab and unfractionated heparin failed to reduce the rate of the primary end point and increased the risk of bleeding.
ISAR-REACT 4: Major Results at 30 Days
| End point | Abciximab plus heparin (%) | Bivalirudin (%) | Relative risk (95% CI) | p |
| Death/large MI/urgent target vessel revascularization/major bleeding* | 10.9 | 11.0 | 0.99 (0.74–1.32) | 0.94 |
| Death, any MI/ urgent target vessel revascularization | 12.8 | 13.4 | 0.96 (0.74–1.25) | 0.76 |
| Major bleeding | 4.6 | 2.6 | 1.84 (1.10–3.07) | 0.02 |
*Primary end point
Use Bivalirudin for MI Patients Only?
Kastrati says that with all the ISAR-REACT trials and the HORIZONS trial (which showed a benefit of bivalirudin over a GP IIb/IIIa blocker plus heparin in STEMI patients), a clear strategy for bivalirudin use in the cath lab can be formulated. "In the ISAR-REACT-1 and ISAR-REACT-3 trials, there was no benefit of bivalirudin over heparin in stable patients or unstable patients without troponin elevations, so we can now build up a strategy of how to use bivalirudin in the cath lab. It appears that bivalirudin is worth using in MI patients (STEMI or NSTEMI), but not in stable patients or in unstable patients without troponin elevations."
He estimates that STEMI and NSTEMI patients together make up about one-third of all patients undergoing PCI. "The other two-thirds may just as well receive heparin, as there is no benefit of using bivalirudin and it is much more expensive," Kastrati told heartwire .
He says after all these trials, there doesn't appear to be any role for GP IIb/IIIa blockers (apart from bailout).
Kastrati commented to heartwire that bivalirudin had taken off much better in the US than in Europe. "The Americans embrace new therapies much more quickly than the Europeans, so they are using bivalirudin more than we are at present. The Europeans are much more conservative, especially with regard to expensive new drugs. I believe our results will persuade more European cardiologists to use bivalirudin in the cath lab at least for the one-third of patients with MI."
Others Say Bivalirudin Best for All PCI Patients
In his review of the ISAR-REACT 4 trial, designated discussant Dr Deepak Bhatt (Brigham and Women's Hospital, Boston, MA) concluded that "the results probably serve as a final chapter in the story of the preferred anticoagulant in PCI. Coupled with HORIZONS-AMI, data from ISAR-REACT 4 support the use of bivalirudin across the full spectrum of ACS."
Bhatt told heartwire that, unlike Kastrati, he uses bivalirudin in all his PCI patients, including those with lower-risk ACS and those with stable disease. He said that earlier studies had shown bivalirudin to have an advantage over high-dose heparin in these lower-risk patients, and although practice has now moved toward low-dose heparin, this has not been studied enough to reach firm conclusions. "But I don't think heparin alone is optimal care for any PCI patients anymore. I can see that in most countries the practice might be to use heparin in lower-risk patients for cost reasons, as the absolute benefit of bivalirudin may not be so much, but I would think there would still be a benefit."
He added: "Another factor is that bivalirudin is easier to use than heparin. With heparin, you have to measure clotting time, and it is difficult to send a patient home quickly. And I also don't like having multiple agents in the cath lab, so I just use bivalirudin for all, with a GP IIb/IIIa blocker for bailout."
Dr Gregg Stone (Columbia University, New York, NY) said that the results of ISAR-REACT 4 were "completely in line" with the larger ACUITY trial, of which he was lead investigator. "We showed in that trial that NSTEMI patients undergoing PCI treated with bivalirudin rather than heparin plus a GP IIb/IIIa inhibitor have similar ischemic outcomes but benefit substantially by a reduction in bleeding and thrombocytopenia. Thus, with the publication of this second confirmatory trial, the evidence is now very solid that bivalirudin should be considered the anticoagulant agent of choice in all patients with ACS undergoing PCI, both NSTEMI and STEMI."
Regarding patients undergoing elective PCI without ACS, Stone says that the same findings were shown in REPLACE-2 and ISAR-REACT 3--"bivalirudin results in less bleeding and thrombocytopenia than heparin or heparin plus a GPIIb/III inhibitor, with trends toward less mortality."
He adds that in a study of more than 127 000 patients from the Premier Perspective database, bivalirudin use was associated with a 33% reduction in transfusions from bleeding and a 49% reduction in in-hospital mortality, both in patients with and without ACS. "So if one believes in evidence-based medicine, bivalirudin should be used in almost all patients undergoing PCI, to prevent iatrogenic complications and save lives," he argues.
Heartwire from Medscape © 2011 Medscape, LLC
Cite this: Bivalirudin Preferable to Abciximab/Heparin in NSTEMI - Medscape - Nov 13, 2011.
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