Feasibility and safety of early initiation of a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor in patients with acute myocardial infarction undergoing primary PCI

• Published in: European heart journal Vol. 41; no. Supplement_2
• Main Authors: Okada, T, Tsushima, R, Taya, S, Saito, E, Takagi, W, Sogo, M, Ugawa, S, Nosaka, K, Takahashi, M, Okawa, K, Sakane, K, Miyoshi, T, Ito, H, Doi, M
• Format: Journal Article
• Language: English
• Published: 01.11.2020
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/ehjci/ehaa946.3340

Abstract Background Recent ESC/EAS Guidelines for the management of dyslipidemia stated that the treatment goal of LDL cholesterol (LDL-C) in very high-risk patients is less than 55mg/dl. PCSK9 inhibitors in addition to strong statins could be a useful strategy for rapid and aggressive lowering of LDL-C. However, the feasibility and safety of early initiation of a PCSK9 inhibitor for AMI patients undergoing primary PCI remain unclear. Objectives We examined the effects of early initiation of a PCSK9 inhibitor, evolocumab, on lipid profile and inflammatory markers and its safety in AMI patients undergoing primary PCI. Methods This study is a single center, randomized, controlled trial involving 102 patients hospitalized for AMI. The patients were randomly assigned 1:1 to the evolocumab group and the control group. Evolocumab (140 mg) was subcutaneously injected within 24 hours after PCI and then every two weeks. All patients received pitavastatin (2mg/day) in addition to the allocated treatment. The primary endpoints were changes in lipid profile and inflammatory markers from baseline to 4 weeks. Results 102 patients were enrolled between October 2017 and December 2019. 89 patients were ST-segment elevation myocardial infarction (STEMI), 13 patients were non-STEMI. Primary PCI was successfully performed in all patients. 76 patients were statin-naïve. 2 patients were excluded from analyses because they died severe heart failure in acute phase. Finally, 100 patients (evolocumab; n=51 and control; n=49) were analyzed. Baseline LDL-C was 121.6±30.3 mg/dl in the evolocumab group and 124.7±33.6 mg in the control group. Change in LDL-C from the baseline to 4 weeks was −92.4±32.4 mg/dl (−75%) in the evolocumab group and −44.8±32.1 mg/dl (−33.1%) in the control group (mean difference; 47.6mg/dl, 95% CI; 34.8 to 60.4 mg/dl, p<0.001). LDL-C <70mg/dl at 4 weeks was achieved in 96.0% of the evolocumab group as compared with 26.5% of the control group. Further, in the evolocumab group. LDL <55mg/dl was achieved in 92.1% at 2 weeks and 92.1% at 4 weeks. Regarding inflammatory markers, there were no significant difference in change in high-sensitivity C-reactive protein (p=0.49) and tumor necrosis factor-alpha (p=0.63) between two groups even after adjustment of baseline value. No adverse event associated with evolocumab was observed during this study. Conclusion In patients with AMI undergoing primary PCI, early initiation of evolocumab rapidly reduced LDL-C without no adverse event, and achieved LDL-C<55mg/dl in most patients within 2 weeks. Early administration of a PCSK9 inhibitor combined with a strong statin could be a feasible and safe treatment for AMI patients undergoing PCI. Funding Acknowledgement Type of funding source: None