scholarly journals Interleukin‐1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST‐Segment–Elevation Myocardial Infarction

2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Antonio Abbate ◽  
Cory R. Trankle ◽  
Leo F. Buckley ◽  
Michael J. Lipinski ◽  
Darryn Appleton ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Response ◽  
Interleukin 1 ◽  
Acute Inflammatory Response ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment

253Effects of Interleukin-1 blockade with Anakinra on cardiac function in ST-segment elevation acute myocardial infarction: results from the VCUART3 echocardiography study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Abbate ◽  
D Kadariya ◽  
H Medina De Chazal ◽  
J G Chiabrando ◽  
C R Trankle ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Placebo Group ◽  
Inflammatory Response ◽  
Cardiac Function ◽  
Interleukin 1 ◽  
Acute Inflammatory Response ◽  
Once Daily ◽  
St Segment Elevation ◽  
St Segment

Abstract Background ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response further promoting cardiac dysfunction and heart failure (HF). Pilot proof-of-concept studies with anakinra, recombinant Interleukin-1 (IL-1) receptor antagonist, have shown feasibility and safety of IL-1 blockade in patients with STEMI. In the current study we analyzed the effects of anakinra on left ventricular (LV) dimensions and function in patients with STEMI. Methods We enrolled patients with STEMI within 12 hours of presentation at 3 sites in the United States of America. After revascularization, patients were randomly assigned to receive anakinra 100 mg twice daily, anakinra 100 mg once daily alternated with placebo once daily every 12 hours, or placebo twice daily, for 14 days in a 1:1:1 ratio. A transthoracic echocardiogram was completed within 24 hours of admission and at 1 year follow up to measure LV end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), stroke volume (SV) and ejection fraction (LVEF). (ClinicalTrials NCT01950299) Results Paired echocardiography studies (follow up study obtained 362 days [336–375] after the baseline study) were available in 63 of the 99 patients (63%): 23 of 35 patients in the placebo group (66%) and 40 of the 64 patients in the anakinra group (62%, P>0.05 for missing studies between the 2 groups; P>0.05 for duration of follow up). Baseline LVEDV, LVESV, SV and LVEF was not significantly different comparing placebo and anakinra (all P>0.05). Patients treated with anakinra had a significant improvement in LVEF from 49.8% (41.8–60.0%) to 54.0% (46.0–58.4%, P=0.028) and SV from 43.6 ml (37.6–52.1 ml) to 48.7 ml (40.9–62.5 ml, P=0.008), whereas no significant changes occurred within the placebo group (LVEF: from 51.7% [40.1–56.0%] to 53.5% [43.4–59.4%], P=0.25; SV: from 47.7 ml [40.1–56.8 ml], to 53.0 ml [44.9–57.4 ml], P=0.81). The between-groups differences, however, were not statistically significant. No significant changes were noted in LVEDV and LVESV in either group. The interval changes in CRP between admission and 72 hours, expression of the acute inflammatory response, inversely correlated with the LVEF at follow up (R=-0.30, P=0.026), with higher levels of CRP corresponding to lower LVEF values Conclusions A significant improvement in cardiac systolic function was seen in patients treated with IL-1 receptor antagonist, anakinra, following STEMI, and not in patients with placebo. Further studies are however required to determine whether the benefits of IL-1 blockade in the prevention and treatment of HF are mediated by the effects on cardiac function. Acknowledgement/Funding Funded by NHLBI 1R34HL121402; Drug supply from Swedish Orphan Biovitrum

scholarly journals Helicobacter pylori Seropositivity in Patients with Interleukin-1 Polymorphisms Is Significantly Associated with ST-Segment Elevation Myocardial Infarction

PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166240 ◽  
Author(s):  
Noriaki Tabata ◽  
Daisuke Sueta ◽  
Tomonori Akasaka ◽  
Yuichiro Arima ◽  
Kenji Sakamoto ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Helicobacter Pylori ◽  
Interleukin 1 ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment

Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Van Tassell ◽  
G.F Wohlford ◽  
A.C Ho ◽  
A Vecchie ◽  
C Garmendia ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Inflammatory Response ◽  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Pooled Analysis ◽  
Funding Source ◽  
St Segment Elevation ◽  
Interleukin 1 Receptor Antagonist ◽  
St Segment

Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P<0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)

Interleukin-1 blockade with Anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials

2021 ◽  
Author(s):  
Antonio Abbate ◽  
George F Wohlford ◽  
Marco Giuseppe Del Buono ◽  
Juan Guido Chiabrando ◽  
Roshanak Markley ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Clinical Trials ◽  
Interleukin 1 ◽  
Pooled Analysis ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Serious Infections ◽  
New Onset

Abstract Aims ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. Methods and Results We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1 year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analyzed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-Reactive-Protein between baseline and 14 days (75.48 [41.7–147.47] vs 222.82 [222.82 [117.22–399.28] mg•day/L, P < 0.001) Conclusions IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new onset HF or hospitalization for HF at 1 year following STEMI.

scholarly journals Improved Cardiac Function and Attenuated Inflammatory Response by Additional Administration of Tirofiban during PCI for ST-Segment Elevation Myocardial Infarction Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jing Zhang ◽  
Guomin Ding
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Response ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Time Dependent ◽  
Left Ventricular Ejection ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Tnf Α

ST-segment elevation myocardial infarction (STEMI) is one of the acute coronary syndromes, and it is the main cause of cardiac death worldwide. The purpose of this study was to investigate whether tirofiban improves cardiac function and attenuates inflammatory response in STEMI patients undergoing percutaneous coronary intervention (PCI). From May 2016 to May 2019, a total of 124 patients who admitted into our hospital due to STEMI fulfilled inclusion and exclusion criteria and were randomly assigned to PCI + tirofiban and PCI groups, 62 cases per groups. Intravenous administration of 10 μg kg−1 min−1 tirofiban was performed 30 min prior to PCI. During PCI, tirofiban infusion through a micropump with 0.15 μg kg−1 min−1 lasted for 48 h. It was found that the PCI + tirofiban group was significantly different from the PCI group in total corrected TIMI frame count (CTFC) after PCI (15.88 ± 5.11 vs. 22.47 ± 6.26, P < 0.001 ). At day 7 and day 30 post-PCI, a significant time-dependent decrease in the levels of brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and creatine kinase isoenzyme (CK-MB) in both groups was observed after PCI ( P < 0.001 ). More importantly, the patients in the PCI + tirofiban group had much lower levels of BNP, cTnI, and CK-MB compared with those in the PCI group at days 7 and 30 post-PCI ( P < 0.001 ). At day 7 following PCI, the left ventricular ejection fraction (LVEF) was statistically higher in the PCI + tirofiban group than in the PCI group ( P < 0.05 ). At day 30 post-PCI, increased LVEF concomitant with reduced left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) was observed in the PCI + tirofiban group compared with the PCI group. At day 7 and day 30 post-PCI, both groups displayed a time-dependent decline in the levels of C reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and procalcitonin (PCT) after PCI ( P < 0.05 ). Additionally, the patients in the PCI + tirofiban group had lower levels of CRP, TNF-α, IL-6, and PCT compared with those in the PCI group at days 7 and 30 post-PCI ( P < 0.05 ). All patients in the PCI + tirofiban and PCI groups were followed up for 12 months by outpatient or telephone after discharge. There were fewer patients with LVEF < 50% in the PCI + tirofiban group than the PCI group ( P = 0.044 ). Furthermore, it was found that the incidence rate of major adverse cardiovascular events (MACEs) in the PCI + tirofiban group was evidently lower than that in the PCI group (12.90% vs. 29.03%, P = 0.028 ). Taken together, our data suggest that additional administration of tirofiban could improve cardiac function and attenuate inflammatory response in STEMI patients undergoing PCI, which is worthy of promotion in clinic.

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