Comparison of Efficacy and Safety of Recombinant Human Prourokinase and Alteplase in the Treatment of STEMI and Analysis of Influencing Factors of Efficacy

Liu, Yizhou; Yang, Yu‐Lin; Li, Ying; Peng, Xiaoqing

doi:10.1155/2021/6702965

Cited by 4 publications

(6 citation statements)

References 18 publications

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“…15 Previous research found that prourokinase, as a novel and fibrin-specific anticoagulant, not only effectively recanalized blood vessels and improve the cardiac function of patients with STEMI, but also had very low rate of bleeding complications, which may provide an alternative and appropriate thrombolytic drug option for STEMI patients. 19,20 Besides, this study showed that patients receiving thrombolysis alone had worse in-hospital ischemic outcomes. Previous studies have shown that plaque rupture and plaque erosion are the 2 most common underlying mechanisms for sudden cardiac death and acute coronary syndrome.…”

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Reperfusion strategies in patients with ST-segment elevation myocardial infarction during hospitalization in China: Findings from the Improving Care for Cardiovascular disease in China (CCC)-Acute Cronary Synrome project

Wang,

Zhang,

et al. 2023

Preprint

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ObjectiveTo analyze the current situation of reperfusion strategies of ST-segment elevation myocardial infarction (STEMI) in China and evaluate the efficacy and safety of different reperfusion strategies, especially pharmaco-invasive percutaneous coronary intervention (PI-PCI).MethodsThe CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project is a joint study between the American Heart Association and Chinese Society of Cardiology (CSC). STEMI patients who were recruited to the CCC-ACS project between November 2014 and December 2019 and admitted within 48 hours after symptom onset and treated by thrombolysis or percutaneous coronary intervention (PCI) were included in this cohort study. The primary efficacy outcomes were major adverse cardiac cerebrovascular events (MACCEs) that occurred during hospitalization. The primary safety outcomes were Thrombolysis in Myocardial Infarction (TIMI) major or minor bleedings criteria during hospitalization. Univariate regression logistic analysis, multivariable logistic regression analysis, propensity score-matched analysis, and inverse probability of treatment weighting analysis were performed to evaluate the efficacy and safety of different reperfusion strategies.ResultsOf 37733 STEMI patients, 35019 patients received primary percutaneous coronary intervention (PPCI), 999 patients received thrombolysis and 1715 patients received PI-PCI. Compared with PPCI, the thrombolysis group had higher incidence of all cause death (1.6% vs 2.8%, P =0.003), MACCEs (2.0% vs 3.6%, P < 0.001), and TIMI major bleedings (1.2% vs 2.2%, P=0.007). In the PI-PCI group, the incidence of MACCEs (2.0% vs 0.8%, P =0.001), all cause death (1.6% vs 0.4%, P =0.001), and cardiac death (1.5% vs 0.4%, P =0.001) were significantly lower than PPCI group; and the same conclusion was found in the subgroup of in time from first medical contact(FMC) to reperfusion ≥ 3h. However, the risk of TIMI minor bleedings (5.1% vs 6.7%, P=0.008) was higher in the PI-PCI group in the subgroup of in time from FMC to reperfusion ≥ 3h. Compared with timely PPCI group, the incidence of all cause death was significantly lower and the incidence of heart failure was higher in the scheduled PCI group. Compared with late PPCI group, the incidence of all cause death, MACCEs were significantly lower in scheduled PCI group. Compared with timely PPCI, the ratio of heart failure was statistically significant higher in the rescue PCI group. There was no significant difference in all outcomes in all models between rescue PCI group and late PPCI group. Moreover, compared with scheduled PCI ≤ 24h group, the scheduled PCI during 24h to 7d group had lower risk of TIMI major or minor bleedings and the scheduled PCI >7d group had the similar risk of bleedings; the scheduled PCI >7d group had lower risk of heart failure.ConclusionsThis study demonstrates that in STEMI patients who could not perform timely PPCI, PI-PCI is feasible, including rescue PCI,which can reduce the rate of MACCEs and mortality during hospitalization.But the increased risk of bleedings also should be noted.In scheduled PCI after successful thrombolysis, appropriate extension the time window of scheduled PCI can be considered under stable clinical conditions.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Reperfusion strategies in patients with ST-segment elevation myocardial infarction during hospitalization in China: Findings from the Improving Care for Cardiovascular disease in China (CCC)-Acute Cronary Synrome project

Wang,

Zhang,

et al. 2023

Preprint

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“…U is the flow velocity in the clot, which is calculated from Darcy’s law:

where k is the permeability of the clot in unit

. It is calculated from the Davis equation, and further details can be found in Piebalgs et al [ 18 ].

is the dynamic visocity in unit

, and

is the pressure drop per unit length of the clot.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, none of these tPA variants has shown better functional clinical outcomes than alteplase for AIS treatment so far [ 11 , 14 ]. Recent clinical research from developing countries found that IV urokinase and its precursor, pro-urokinase, seem to have similar efficacy and safety to alteplase in treating mild to moderate AIS, while the cost of urokinase is only one-tenth of that of alteplase [ 15 , 16 , 17 , 18 , 19 , 20 ]. These contested clinical results did not fully reflect the theoretical advantage of drugs as scientists expected.…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke

Yang

2023

Pharmaceutics

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Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intravenous AIS therapy by computational simulations of the pharmacokinetics and pharmacodynamics combined with a local fibrinolysis model. The performances of the drugs are evaluated by comparing clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time from drug administration to clot lysis. Our results reveal that urokinase has the quickest lysis completion but the highest ICH risk due to excess fibrinogen depletion in systemic plasma. While tenecteplase and alteplase have very similar thrombolysis efficacy, tenecteplase has a lower risk of ICH and better resistance to PAI-1. Among the four simulated drugs, reteplase has the slowest fibrinolysis rate, but fibrinogen concentration in systemic plasma is unaffected during thrombolysis.

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“…Recombinant human prourokinase (Pro-UK) is a fibrin-specific plasminogen activator that shares structural similarities with tissue plasminogen activator but functions via a different mechanism ( 8 ). Studies show that Pro-UK presents with fewer hemorrhagic complications and lower re-occlusion rate in patients with acute STEMI compared with conventional drugs ( 9 , 10 ). In addition, certain prospective study found that Pro-UK decreases MACEs whereas a retrospective study revealed that Pro-UK does not affect MACEs ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of intracoronary recombinant human prourokinase administration in patients with acute myocardial infarction and ST‑segment elevation: A meta‑analysis of randomized controlled trials

Fan

Jiao

et al. 2022

Exp Ther Med

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group. No significant heterogeneity was identified across these selected studies. Pro-UK therapy significantly decreased the incidence of major adverse cardiac events [risk ratio (RR), 0.68; 95% CI, 0.56-0.82, P<0.0001], left ventricular end-diastolic diameter [standardized mean difference (SMD), -0.26; 95% CI, -0.40 --0.12; P= 0.0003], corrected thrombolysis in myocardial infarction (TIMI) frame count [SMD, -0.45; 95% CI, -0.62 --0.28; P<0.00001] and cardiac troponin I [SMD, -0.31; 95% CI, -0.46 --0.17; P<0.0001]. In addition, Pro-UK administration increased TIMI grade 3 flow (RR, 1.16; 95% CI, 1.07-1.25; P=0.0003), TIMI myocardial perfusion grade 3 (RR: 1.39, 95% CI: 1.12-1.74, P= 0.004), ST-segment resolution (RR, 1.23; 95% CI, 1.10-1.36; P= 0.0002) and left ventricular ejection fraction (SMD, 0.38; 95% CI, 0.27-0.49; P<0.00001). No significant difference was identified in bleeding (RR, 1.12; 95% CI, 0.85-1.47; P= 0.41). The present meta-analysis determined that intracoronary Pro-UK administration is efficacious and safe to decrease slow blood flow or no reflow phenomena following PCI and improve the prognosis of patients with acute STEMI.

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Comparison of Efficacy and Safety of Recombinant Human Prourokinase and Alteplase in the Treatment of STEMI and Analysis of Influencing Factors of Efficacy

Cited by 4 publications

References 18 publications

Reperfusion strategies in patients with ST-segment elevation myocardial infarction during hospitalization in China: Findings from the Improving Care for Cardiovascular disease in China (CCC)-Acute Cronary Synrome project

Reperfusion strategies in patients with ST-segment elevation myocardial infarction during hospitalization in China: Findings from the Improving Care for Cardiovascular disease in China (CCC)-Acute Cronary Synrome project

In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke

Safety and efficacy of intracoronary recombinant human prourokinase administration in patients with acute myocardial infarction and ST‑segment elevation: A meta‑analysis of randomized controlled trials

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