Impact of In-Hospital PCSK9 Inhibition on Myocardial Inflammation After Myocardial Infarction

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 (SUVmean) 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 SUVmean 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 SUVmean 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 (SUVmean) and global longitudinal strain in all study participants at 30 days (r = 0.25; P = 0.044). (B) Scatterplot depicting the association between SUVmax 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 (SUVmean) 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 SUVmean 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 SUVmean 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…