Percutaneous Coronary Intervention after Fibrinolysis for ST-Segment Elevation Myocardial Infarction Patients: An Updated Systematic Review and Meta-Analysis

<div><p>Background</p><p>Percutaneous coronary intervention (PCI), fibrinolysis and the combination of both methods are current therapeutic options for patients with ST-segment elevation myocardial infarction (STEMI).</p><p>Methods</p><p>We searched PubMed, EMBASE, Google scholar and Cochrane Controlled Trials Register for randomized controlled trials (RCTs) evaluating the efficacy and safety of PCI after fibrinolysis within 24 hours, which was compared with primary PCI alone and ischemia-guided or delayed PCI. Meta-analysis was conducted using Review Manager 5.30 following the methods described by the Cochrane library.</p><p>Results</p><p>A total of 16 studies including 10,034 patients were enrolled. As compared with primary PCI alone group, the short-term mortality (5.8% vs 4.5%, RR 1.29, 95% confidence interval [CI] 1.00–1.65) and re-infarction rate (4.1% vs 2.7%, RR 1.46, 95%CI 1.05–2.03) were higher in the immediate PCI group (median/mean time ≤ 2 h after fibrinolysis). However, the short-term mortality and re-infarction rate showed no statistically significant differences in the early PCI group (2–24 hours after fibrinolysis). The rate of major bleeding events was higher both in the immediate PCI (6.3% vs 4.4%, RR 1.43, 95%CI 1.11–1.85) and the early PCI group (6.4% vs 4.4%, RR 1.46, 95%CI 1.03–2.06) as compared with primary PCI alone group. As compared with ischemia-guided or delayed PCI, early PCI was associated with significantly reduced re-infarction (2.4% vs 4.0%, RR 0.61, 95%CI 0.41–0.92) and recurrent ischemia (1.5% vs 5.3%, RR 0.29, 95%CI 0.12–0.70) at short-term. And the reduced re-infarction rate was also observed at long-term.</p><p>Conclusions</p><p>Early PCI after fibrinolysis, with a relatively broader time for PCI preparation, can bring the similar effects with primary PCI alone and is better than ischemia-guided or delayed PCI in STEMI patients with symptom onset < 12 h who cannot receive timely PCI. However, immediate PCI after fibrinolysis is detrimental.</p></div

Long-term mortality for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus ischemia-guided or delayed PCI.

<p>Long-term mortality for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus ischemia-guided or delayed PCI.</p

Characteristics of the included trials.

<p>Abbreviations</p><p>^<b>a</b>. A = the primary PCI alone group, B = the immediate or early PCI group</p><p>^<b>b</b>. low risk, i.e., if they were < 60 years old and had a localized inferior infarction</p><p>^<b>c</b>. The description of age and time was median or mean value</p><p>^<b>d</b>. Two 5-U boluses separated by 30 minutes for those < 75 years old, one 5-U dose for those ≥ 75 years old</p><p>(Immediate or early PCI after fibrinolysis versus primary PCI alone).</p

The flow chart of literature inclusion.

<p>(Flow Diagram).</p

Short-term mortality for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus primary PCI alone.

<p>Short-term mortality for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus primary PCI alone.</p

Long-term re-infarction for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus ischemia-guided or delayed PCI.

<p>Long-term re-infarction for immediate or early percutaneous coronary intervention (PCI) after fibrinolysis versus ischemia-guided or delayed PCI.</p

Effect of LZ-207 on HCT116 cell growth when co-cultured with LPS-induced THP-1 cells.

<p>(A) HCT116 cells were seeded at a density of 4 × 10⁴ cells/well with or without THP-1 cells stimulated with LPS in the presence or absence of LZ-207. After 24 h, the co-culture was stopped, and the viability of the HCT116 cells was measured via MTT assay. (B-C) Western blotting analysis of PCNA protein levels in co-cultured HCT116 cells. The data are presented as the mean ± SD (n = 3). *<i>P</i> < 0.05, **<i>P</i> < 0.01, significant difference compared with the control.</p

Effect of LZ-207 on NF-κB expression in LPS-treated HCT116 cells.

<p>HCT116 cells were treated with or without LZ-207 in the presence of LPS for 1 h. After isolating the nuclear and cytoplasmic extracts, (A) NF-κB p65 levels were determined by immunofluorescence, and (B-C) NF-κB p65 translocation was measured via Western blotting. (D) LZ-207 suppressed LPS-induced NF-κB DNA binding activity in a concentration-dependent manner, as detected via EMSA assay. (E-H) Western blotting analysis of the phosphorylation of IκB and IKK in HCT116 cells treated with or without LZ-207 in the presence of LPS for 1 h. The data are presented as the mean ± SD (n = 3). *<i>P</i> < 0.05, **<i>P</i> < 0.01, significant difference compared with the control.</p

The chemical structures of flavone and LZ-207.

<p>(A) Chemical structure of the 15-carbon flavone backbone. (B) Chemical structure of LZ-207 (C₂₆H₃₂N₂O₆, MW = 468.5421).</p

Effect of LZ-207 on the expression of inflammation-related genes in THP-1 human monocyte cells.

<p>(A-B) The levels of IL-6 and IL-1β in the culture medium were measured using ELISA kits following treatment with LPS in the presence or absence of different concentrations of LZ-207 in THP-1 cells. (C-D) Total RNA was obtained from THP-1 cells stimulated with LPS in the presence or absence of LZ-207 using a TRIzol reagent kit. The mRNA levels of IL-6 and IL-1β were measured using RT-PCR. β-actin was used as an internal control. The data are presented as the mean ± SD (n = 3). *<i>P</i> < 0.05, **<i>P</i> < 0.01, significant difference compared with the control.</p