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Safety, tolerability and effects of a single subcutaneous administration of SP16-a SERPIN-like, small peptide agonist of the Low-Density Lipoprotein-like Receptor 1 -on the acute inflammatory response in patients with ST-segment elevation Myocardial Infarction (STEMI)

J Cardiovasc Pharmacol. 2022 Jul 12. doi: 10.1097/FJC.0000000000001331. Online ahead of print.


BACKGROUND: Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based upon the anti-inflammatory and cytoprotective properties mediated by the engagement of the Low-Density Lipoprotein Related Protein 1 (LRP1) receptor. SERPIN Peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function.

METHODS: Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention (PCI) in a single-center, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N=28) with similar enrollment criteria.

RESULTS: All ten patients with STEMI received subcutaneous administration of SP16, 381 [272 to 478] minutes after PCI, without any treatment-related adverse events. The area under the curve (AUC) for C reactive protein (CRP) was 133 [46 to 528] mg•day/L in the SP16 treated group versus 286 [141 to 581] mg•day/L in the historical placebo-treated group (p=0.161). The AUC for creatine kinase-myocardial band (CK-MB) was 1,432 [675 to 3,089] ng•day/mL in the SP16-treated group versus 2,367 [830 to 4,750] ng•day/mL in the historical placebo-treated patients (p=0.428). Left ventricular ejection fraction (LVEF) was 46% [39 to 54] at baseline and 51% [46 to 58] at 1 year follow up in SP16 treated patients (interval change 5% [-0.3% to +9%] p=0.05) and 44% [38% to 56%] at baseline and 53% [43% to 59%] at 1 year follow up in historical placebo-treated patients (interval change 3% [-5% to 10%], p=0.305).

CONCLUSION: A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based upon formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI.

PMID:35881895 | DOI:10.1097/FJC.0000000000001331

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