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Efficacy and Safety of EdifoligideEfficacy and Safety of Edifoligide

JAMA. 2006;295(13):1513-1515. doi:10.1001/jama.295.13.1513-a
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

EFFICACY AND SAFETY OF EDIFOLIGIDE

To the Editor: In the PREVENT (Project of Ex-vivo Vein Graft Engineering via Transfection) IV study, the PREVENT IV investigators1 found a high proportion of saphenous vein graft failure (VGF) (>25% of grafts) occurring within the first 12 to 18 months after coronary artery bypass graft (CABG) surgery, with more than 40% of the patients who underwent CABG surgery having at least 1 graft occluded within this period. Moreover, pretreatment of harvested saphenous veins with the E2F transcription factor decoy edifoligide with the aim of preventing neointimal hyperplasia and accelerated atherosclerosis did not reduce the failure rate of the venous conduits. The PREVENT IV investigators suggest that a substantial proportion of venous graft failures takes place early in the perioperative period as major adverse cardiac events occur soon after surgery, more frequently in association with graft failure, but they do not provide an explanation for this phenomenon.

Early occlusion of venous conduits is concomitant with significant perturbations of the hemostatic and fibrinolytic system. During the intraoperative period, the prothrombotic burst occurs mainly in patients undergoing CABG surgery with the use of cardiopulmonary bypass (on-pump), but an increase in thrombin generation is detectable both in on-pump and off-pump CABG surgery up to at least 2 months after surgery.2 4 This suggests that patients undergoing CABG surgery are at risk of developing thrombosis irrespective of the use of cardiopulmonary bypass.

Thus, the prothrombotic postoperative status is likely responsible for the consistent VGF rate observed by the PREVENT IV investigators. This supports the concept that currently recommended postoperative antithrombotic therapy for these patients (low-dose aspirin)5 is not sufficient for the prevention of VGF. The use of antithrombotic strategies specifically targeted against the generation of thrombin should be considered in future trials in patients undergoing CABG surgery.

Financial Disclosures: None reported.

References
PREVENT IV Investigators.  Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial.  JAMA. 2005;2942446-2454
Parolari A, Colli S, Mussoni L.  et al.  Coagulation and fibrinolytic markers in a two-month follow-up of coronary bypass surgery.  J Thorac Cardiovasc Surg. 2003;125336-343
Parolari A, Mussoni L, Frigerio M.  et al.  Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.  J Thorac Cardiovasc Surg. 2005;130303-308
Parolari A, Mussoni L, Frigerio M.  et al.  The role of tissue factor and P-selectin in the procoagulant response that occurs in the first month after CABG and OPCAB.  J Thorac Cardiovasc Surg. 2005;1301561-1566
Stein PD, Schunemann HJ, Dalen JE, Gutterman D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;126(3 suppl)  600S-608S

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PREVENT IV Investigators.  Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial.  JAMA. 2005;2942446-2454
Parolari A, Colli S, Mussoni L.  et al.  Coagulation and fibrinolytic markers in a two-month follow-up of coronary bypass surgery.  J Thorac Cardiovasc Surg. 2003;125336-343
Parolari A, Mussoni L, Frigerio M.  et al.  Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.  J Thorac Cardiovasc Surg. 2005;130303-308
Parolari A, Mussoni L, Frigerio M.  et al.  The role of tissue factor and P-selectin in the procoagulant response that occurs in the first month after CABG and OPCAB.  J Thorac Cardiovasc Surg. 2005;1301561-1566
Stein PD, Schunemann HJ, Dalen JE, Gutterman D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;126(3 suppl)  600S-608S
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