PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection

Navarese, Eliano P., Podhajski, Przemysław, Gurbel, Paul A., Grzelakowska, Klaudyna, Ruscio, Eleonora, Tantry, Udaya, Magielski, Przemysław, Kubica, Aldona, Niezgoda, Piotr, Adamski, Piotr, Junik, Roman, Przybylski, Grzegorz, Pilaczyńska-Cemel, Marta, Rupji, Manali, Specchia, Giuseppe, Pinkas, Jarosław, Gajda, Robert, Gorog, Diana A., Andreotti, Felicita and Kubica, Jacek (2023) PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection. Journal of the American College of Cardiology, 81 (3). pp. 224-234. ISSN 0735-1097
Copy

Background The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. Objectives The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. Methods In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. Results Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%). Conclusions PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)


picture_as_pdf
IMPACT_PCSK9_SIRIOMs.pdf
subject
Submitted Version
copyright
Available under Unspecified

View Download

Atom BibTeX OpenURL ContextObject in Span OpenURL ContextObject Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation METS MODS RIOXX2 XML Reference Manager Refer ASCII Citation
Export

Downloads