Evolocumab Fails to Prevent Saphenous Vein Graft Failure, Major Trial Shows
GENEVA, SWITZERLAND - A closely watched clinical trial, NEWTON-CABG CardioLink-5, has found that the PCSK9 inhibitor evolocumab does not prevent failure of saphenous vein grafts (SVGs) following coronary artery bypass grafting (CABG) surgery. The findings, presented today, challenge the potential for aggressive LDL cholesterol lowering to address a persistent problem in cardiac surgery.
SVG failure remains a significant complication of CABG, impacting long-term patient outcomes and often necessitating repeat revascularization procedures. While evolocumab demonstrably reduces LDL cholesterol – achieving levels comparable to those seen in the landmark FOURIER trial which demonstrated cardiovascular benefit in patients with established disease – the NEWTON-CABG trial showed this reduction did not translate to improved SVG patency. This suggests the mechanisms driving SVG failure are more complex than simply LDL cholesterol levels.
The NEWTON-CABG CardioLink-5 study investigated the effect of evolocumab on SVG patency at 24 months. Despite the LDL reduction, the trial did not demonstrate a statistically significant benefit. Discussant François Mach, MD (Geneva University Hospital, Switzerland), emphasized the trial is not a failure, but rather provides a crucial answer to an crucial clinical question.
“The biology may be different,” noted lead investigator Dr. Sunil Verma, highlighting potential differences in how coronary arteries and SVG respond to treatment. Both Verma and mach pointed to the need for further research into option strategies, including targeting inflammation or thrombosis, and utilizing intraoperative or postoperative imaging to identify technical issues contributing to graft occlusion. Mach also proposed exploring alternative graft sources, such as arteries from animals, to avoid the complications associated with SVGs.
Previous research with evolocumab and alirocumab (Praluent; Sanofi/Regeneron), as demonstrated in the HUYGENS and PACMAN-AMI trials, has shown significant changes in atherosclerotic plaque quality and quantity within 12 months. Though, the NEWTON-CABG trial’s 24-month follow-up period suggests these early benefits may not be sustained in the context of SVG failure.
