BLADE-PCI: Novel liposomal alendronate fails in diabetes
SAN FRANCISCO — Intravenous administration of a novel liposomal formulation of alendronate at the time of PCI with drug-eluting stents failed to reduce restenosis at 9 months in patients with diabetes enrolled in the BLADE-PCI trial.
Known as LABR-312 (BIOrest), the investigational compound is a formulation of alendronate, which is used to prevent and treat osteoporosis. LABR-312 has been shown in animal models to decrease neointimal hyperplasia via transient modulation of circulating monocytes and permanent reduction of monocyte accumulation at vascular injury sites and around stent struts, Philippe Généreux, MD, co-director of the structural heart program at Gagnon Cardiovascular Institute at Morristown Medical Center, New Jersey, and also with the Hospital du Sacré-Couer de Montréal, said during a press conference at TCT 2019.
The BLADE-PCI investigators sought to study the impact of liposomal alendronate in patients with diabetes.
“Diabetes is an important predictor of adverse ischemic events and neointimal hyperplasia after PCI. Diabetes patients also exhibit more aggressive progression of coronary atherosclerosis partly because of heightened systemic inflammation,” Généreux said.
At 9 months, the primary endpoint of in-stent percent neointimal hyperplasia volume, as measured by OCT, was 13.3% for patients who received LABR-312 compared with 14.6% for those who received placebo (difference –1.12%; 95% CI, –3.51 to 1.28; P = .35), Généreux reported during a Late-Breaking Science presentation. When the researchers examined the primary outcome by dose stratification, percent neointimal hyperplasia volume was greatest with the highest 0.08-mg dose, he said.
“No interaction was seen, independently of the insulin or monocyte count status at baseline, or the quality of diabetes control,” he said.
Nine-month OCT showed no significant differences between LABR-312 and placebo in secondary outcomes including neointimal hyperplasia thickness, percent stent strut coverage, neointimal hyperplasia volume, lumen cross-sectional area, stent cross-sectional area and neointimal hyperplasia cross-sectional area.
Nine-month angiographic endpoints were also similar with LABR-312 or placebo, including in-stent late loss (0.29 vs. 0.34; P = .41) and in-stent diameter stenosis (24 vs. 26.2; P = .27) In-stent restenosis with > 50% diameter stenosis was 6.8% in the LABR-312 group vs. 9.4% in the placebo group (P = .5), according to data presented here.
No deaths or stent thrombosis occurred during the 9-month follow-up. Other clinical endpoints were similar at follow-up, including stroke, MI, revascularization, target vessel failure, target lesion failure and MACCE.
BLADE-PCI was a phase 2b, prospective, randomized, double-blind, placebo-controlled trial. Patients were enrolled at sites in Canada, Israel, Poland and the United Kingdom. Patients included had diabetes and were on a background of pharmacologic therapies including insulin and oral or injectable hypoglycemic agents. Most patients had type 2 diabetes and nearly one-third were on insulin. All were undergoing PCI for stable or unstable angina, silent ischemia or non-STEMI. Target lesions were treated with the Resolute DES (Medtronic) during index PCI.
In total, 271 patients were enrolled (358 lesions; mean age, 64 years), with 136 randomly assigned to receive LABR-312 and 135 to placebo. In the investigational therapy group, 43 patients received the 0.1 mg low dose, 48 received the 0.03 mg intermediate dose and 45 received the 0.08 mg high dose. – by Katie Kalvaitis
Généreux P, et al. Late-Breaking Science 4. Presented at: TCT Scientific Symposium; Sept. 25-29, 2019; San Francisco.
Disclosure: Généreux reports he has financial relationships with Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health/Cordis, Cardiovascular Systems Inc., Edwards Lifesciences, Medtronic, Opsens, Pi-Cardia, Puzzle Medical, Saranas, Soundbite Medical Inc., Siemens and SIG.NUM.