Novel Anti-inflammatory May Reduce Restenosis After BMS in High-Risk Patients
Administration of an experimental intravenous anti-inflammatory compound before bare-metal stenting appears safe and reduces late luminal loss specifically in patients at risk for restenosis due to pro-inflammatory states, according to a study published online December 12, 2012, ahead of print in the American Heart Journal.
Investigators led by Shmuel Banai, MD, of the Tel Aviv Medical Center (Tel Aviv, Israel), enrolled 225 patients at 12 Israeli centers as part of the phase II Biorest Liposomal Alendronate with Stenting sTudy (BLAST). Patients were randomized to low-dose (0.001 mg; n = 77) or high-dose LABR-312 (0.01 mg; n = 74) or placebo (n = 74) during implantation with a Presillion BMS (Medinol, Tel Aviv, Israel). LABR-312 (BIOrest, Yanveh, Israel), which specifically targets monocytes, was given intravenously over 2 hours within 30 minutes of predilatation.
Differences Only in Subgroup
At a median follow-up of 180 days, there were no differences in safety, including MACE, death, MI, clinically driven TLR or serious adverse events likely related to the drug between the low- and high-dose groups or either treatment group and the placebo group. For the entire cohort, in-stent late loss, the primary endpoint, was similar between the high- and low-dose treatment groups and placebo (0.81 ±. 0.68, 0.83 ± 0.57, and 0.86 ± 0.60, respectively; P = NS), as were several other angiographic measures.
In a prespecified subgroup analysis, demographic parameters, lesion characteristics, and ACS showed no interaction with a treatment effect. However, in diabetic patients there was a numerical reduction in late loss in both low- and high-dose treatment groups, with the high-dose LABR-312 group experiencing nearly a 30% reduction compared with placebo (0.77 ± 0.62 mm vs. 1.05 ± 0.60 mm; P = 0.16). In addition, in patients with an elevated monocyte count, the high dose of the drug reduced late loss more than 30% compared with placebo (0.67 ± 0.50 mm vs. 1.00 ± 0.62 mm; P = 0.03). No interaction was detected between diabetes status and monocyte count.
Potential for Personalized Medicine
Because the compound is designed to target only monocytes, LABR-312 spares endothelial cells and allows normal healing and use of standard dual-antiplatelet therapy, according to Dr. Banai and colleagues. Although there were no differences in the overall cohort for the primary endpoint, they say their findings add support for the idea of a treatment effect for LABR-312. However, they add that “it is impossible to conclude based on the current data set whether patients could be separated into ‘responders’ and ‘nonresponders’ or whether there was a continuous spectrum of effect.”
As for the late loss reduction in diabetes patients, which did not reach statistical significance, the authors point out that the study was underpowered for this subgroup. The significant impact in patients with a pro-inflammatory state is important, they add, since even in this subgroup, “monocyte levels were within normal limits as set by the individual hospital laboratories.”
The researchers conclude that the ability to identify which patients are most at risk for restenosis and most amenable to a specific therapy may provide the potential for personalized medicine.
Many Have Tried and Failed
But Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview that he was not convinced the experimental compound is any more effective than the 50 or so others that have been developed in an attempt to head off restenosis.
“There has been a long history—25 years now—of people trying to find something that prevents restenosis, and we haven’t been able to find anything,” he said. “So you have to be skeptical.”
Dr. Brener said while the compound itself is “elegant” compared with some that have been tried, the results are a bit misleading since the difference seen in the pro-inflammatory group was driven by the higher late loss in the placebo group.
“The difference [in in-stent late loss with the compound] is not at the level of what we see with drug-eluting stents,” he said. “Yes, it’s better than the placebo, but that’s nothing to write home about.”
As for this compound’s potential for personalized therapy, Dr. Brener said he was doubtful of that as well.
“Theoretically it would be nice,” he commented, “But the idea that you would measure someone’s monocytes before PCI and [use that information] to treat them, that’s more targeting than truly personalized medicine.”
Patients had symptomatic ischemic heart disease from de novo coronary artery lesions with stable or unstable angina and baseline cardiac troponin levels up to 3 times the upper limit of normal.
Banai S, Finkelstein A, Almagor Y, et al. Targeted anti-inflammatory systemic therapy for restenosis: The Biorest Liposomal Alendronate with Stenting sTudy (BLAST). A double blind, randomized clinical trial. Am Heart J. 2013;Epub ahead of print.
- The study was funded by BIOrest.
- The Cardiovascular Research Foundation, which owns and operates TCTMD, is a sponsor/collaborator involved in the BLAST trial.
- Drs. Banai and Brener report no relevant conflicts of interest.