The GENESIS Trial Demonstrates Disappointing Results With Pimecrolimus Eluting Stents

March 31, 2008 By Lauren Ciaglo [mailto: lciaglo@perfuse.org]

SCAI-ACCi2 08-Chicago, IL: Results from the GENESIS trial demonstrate that patients treated with CORIO™ (Pimecrolimus-eluting) stents had worse outcomes compared with individuals treated with SYMBIO™ (dual drug delivery of Pimecrolimus and Paclitaxel) stents or the CoStar® (Paclitaxel-eluting) stents.

This study was a randomized, multi-center study of the pimecrolimus-eluting and paclitaxel-eluting coronary stent system in patients with de novo lesions of the native coronary arteries. The study was terminated early.

The GENESIS trial results were presented by Dr. Stefan Verheye, co-director of the catheterization laboratories at Antwerp Cardiovascular Center, ZNA Middelheim Hospital, Antwerp, Belgium at the SCAI-i2 summit Annual Scientific Sessions today in Chicago.

Pimecrolimus is an anti-inflammatory medication and researchers hypothesized that it would reduce neointimal hyperplasia, which causes in-stent restenosis. Pimecrolimus differs from paclitaxel, in that paclitaxel’s mechanism of action is to inhibit cell division. The Conor SymBio™ dual drug stent is designed to independently release Pimecrolimus and paclitaxel from adjacent reservoirs.

The potential advantages of Corio/SymBio include the fact that
 * Pimecrolimus may act to prevent restenosis without delaying vessel healing
 * Dual drug delivery might be a better solution to prevent restenosis
 * This platform may better control drug delivery with no residual drug

The GENSIS study was a single-blinded study with 248 patients randomized in a 2:2:1 ratio to receive either CORIO™ (n=100), SYMBIO™ (n=97), or CoStar® (n=49) (the control arm) stent implantation. The primary endpoint for the trial was in-stent late lumen loss as seen on coronary angiography at 6 months. Additionally, 30 patients per treatment arm underwent intravascular ultrasound (IVUS) at baseline and 6 month follow-up. Patients in the SYMBIO™ group had lower rate of diabetes (18%) compared with the CORIO™ (32%) or CoStar® (37%) groups.

The device success rates among the CoStar®, SYMBIO™, and CORIO™ groups were 98%, 97.9%, and 92%; the lesion success rates were 100%, 100%, and 98%; and the procedural success rates were 100%, 100% and 94%, respectively.

The primary endpoint of in-stent late loss at 6 months was 0.58 ± 0.58 mm in the CoStar® group, 0.96 ± 0.73 mm in the SYMBIO™ group, and 1.40 ± 0.67 mm in the CORIO™ group. On IVUS, the neointimal volume was greatest in the CORIO™ arm compared with SYMBIO™ arm and the CoStar® arm (41.2 ± 11.5% vs. 27.1 ± 12.4% vs. 16.6 ± 12% respectively).

At the final 6 month follow-up, the rates of major adverse cardiovascular events (MACE-cardiac death, myocardial infarction, Q-MI, non-Q MI, TVR) were 39.0% in the CORIO™ arm, 14.4% in the SYMBIO™ arm, and 2.0% in the CoStar® arm (p<0.0001 both treatment arms were compared with the control). These rates were primarily driven by differences in the rates of target vessel revascularization (TVR) and myocardial infarction (MI) among each of the groups (35.0%, 14.4%, and 2.0%, (TVR) and 8.0%, 1.0%, and 0%, (MI), respectively). Rates of stent thrombosis at 6 months were as follows: 2.0%, 1.0%, and 0%.

Source

 * 1) Late Breaking Clinical Trials Session: SCAI Annual Scientific Sessions in partnership with ACC i2 summit, March 31, 2008 Chicago