Impact of In-Hospital PCSK9 Inhibition on Myocardial Inflammation After Myocardial Infarction: A Randomized Clinical Trial

Abstract

In a randomized trial with 55 participants from the EVACS (Evolocumab in Acute Coronary Syndrome) trials, patients with non-ST-segment elevation myocardial infarction (MI) or ST-segment elevation MI received a single dose of evolocumab or placebo, with myocardial inflammation assessed via ¹⁸F-fluorodeoxyglucose positron emission tomography scans at baseline and at 30 days. Evolocumab significantly reduced inflammation (SUV_mean) compared with placebo. PCSK9 levels at 30 days correlated with SUV_mean, and higher SUV_mean was linked to increased end-systolic volume at 6 months. These findings suggest that early PCSK9 inhibition reduces post-MI myocardial inflammation and may influence cardiac remodeling in the months following the acute event.

Keywords: (18)F-FDG-PET imaging; PCSK9 inhibition; acute myocardial infarction; myocardial inflammation.

Graphical abstract

Figure 1

Study Flowchart for the Main Analysis A total of 86 trial participants underwent ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) imaging during hospital admission. A total of 21 subjects did not undergo 30-day scans because outpatient research studies could not be performed because of the COVID-19 pandemic; because of participant refusal; or because participants were out of the country, hospitalized, or in a rehabilitation facility. In total, 65 participants completed imaging studies at baseline and 30 days. Of these 65 pairs, 10 were excluded caused by unsuccessful suppression of myocardial ¹⁸F-FDG uptake. The final analysis included 55 ¹⁸F-FDG-PET scan pairs: 30 in the placebo and 25 in the evolocumab group.

Figure 2

¹⁸F-FDG-PET Assessment of Myocardial Inflammation in the Peri-infarction and Early Postinfarction Period Standardized uptake value (SUV_mean) decreased from a mean ± SD of 2.4 ± 0.5 to 2.1 ± 0.7 in the placebo (A) and from a mean ± SD of 2.7 ± 0.7 to 1.9 ± 0.5 in the evolocumab (B) group (P = 0.064 and P < 0.001 respectively within each group, compared using the Wilcoxon test). (C) Percentage-changes in SUV_mean from baseline to 30 days for the placebo and the evolocumab groups (P = 0.041 for the group comparison, using the Welch’s t test, with the horizontal line representing the mean value in each group). (D) Representative ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) images in the peri-infarction (top) and 30-day postinfarction (bottom) settings from a participant randomized to placebo (left panels) and a participant randomized to evolocumab (right panels). Placebo n = 30 and evolocumab n = 25. The symbols included in the figures represent the following: ∗P < 0.05 and ∗∗∗P < 0.001.

Figure 3

PCSK9 and Myocardial Inflammation in the Early Postinfarction Period Scatterplot demonstrating a positive correlation between serum proprotein convertase subtilisin/kexin 9 (PCSK9) levels and SUV_mean levels at 30 days in the participants from the placebo group (r = 0.36; P = 0.034). For this analysis we included all participants in the placebo group who had an available sample for the measurement of PCSK9 at day 30 and with an interpretable 30-day ¹⁸FDG-PET scan, n = 35. Abbreviations as in Figure 2.

Figure 4

Myocardial Inflammation and Global Left Ventricular Function in the Early Postinfarction Setting (A) Scatterplot depicting the association between standardized uptake value (SUV_mean) and global longitudinal strain in all study participants at 30 days (r = 0.25; P = 0.044). (B) Scatterplot depicting the association between SUV_max and global longitudinal strain in all study participants at 30 days (r = 0.31; P = 0.011). This analysis includes all participants, placebo and evolocumab groups, with an interpretable 30-day ¹⁸F-FDG-PET scan and available echocardiogram (Placebo = 33 [blue symbols]; Evolocumab= 35 [red symbols]; total n = 68).

Figure 5

Myocardial Inflammation at 30 Days and Cardiac Remodeling Outcomes at 6 Months Postinfarction (A) Scatterplots demonstrating data points representing the median standardized uptake value (SUV_mean) levels at 30 days in those with and without a decrease in left ventricular ejection fraction (EF) from 30 days to 6 months (2.00 [Q1-Q3: 1.74-2.54] vs 1.68 [Q1-Q3: 1.44-2.05] respectively; P = 0.039 using the Mann-Whitney U test). (B) Scatterplots demonstrating data points representing the median SUV_mean levels at 30 days in those with and without an increase in left ventricular end-systolic volume (ESV) from 30 days to 6 months (2.02 [Q1-Q3: 1.74-2.51] vs 1.65 [Q1-Q3: 1.41-1.92] respectively; P = 0.021 using the Mann-Whitney U test). (C) Scatterplots demonstrating data points representing the median SUV_mean levels at 30 days in those with and without an increase in left ventricular end-diastolic volume (EDV) from 30 days to 6 months (2.02 [Q1-Q3: 1.68-2.51] vs 1.68 [Q1-Q3: 1.41-2.05]; P = 0.081 using the Mann-Whitney U test). For this analysis we included all participants, placebo and evolocumab groups, with an interpretable 30-day ¹⁸FDG-PET scan and available 30-day and 6 months echocardiograms (n = 40). The symbol included in the figures represent the following: ∗P < 0.05.