Effect of fibrinolytic therapy on ST-elevation myocardial infarction clinical outcomes during the COVID-19 pandemic:A systematic review and meta-analysis

BACKGROUND ST-elevation myocardial infarction(STEMI)is the result of transmural ischemia of the myocardium and is associated with a high mortality rate.Primary percutaneous coronary intervention(PPCI)is the recommended first-line treatment strategy for patients with STEMI.The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019(COVID-19)pandemic,leading to a projected steep rise in mortality.These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion.It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints.AIM To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes.METHODS PubMed,Google Scholar,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic.Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality.Data were meta-analyzed using the random effects model to derive odds ratios(OR)and 95%confidence intervals.Quality assessment was carried out using the Newcastle-Ottawa scale.RESULTS Fourteen studies including 50136 STEMI patients(n=15142 in the pandemic arm;n=34994 in the pre-pandemic arm)were included.The mean age was 61 years;79%were male,27%had type 2 diabetes,and 47%were smokers.Compared with the pre-pandemic period,there was a significantly increased overall incidence of fibrinolysis during the pandemic period[OR:1.80(1.18 to 2.75);I2=78%;P=0.00;GRADE:Very low].The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting.The countries with a low-and middle-income status reported a higher incidence of fibrinolysis[OR:5.16(2.18 to 12.22);I2=81%;P=0.00;GRADE:Very low]and an increased risk of all-cause mortality in STEMI patients[OR:1.16(1.03 to 1.30);I2=0%;P=0.01;GRADE:Very low].Meta-regression analysis showed a positive correlation of hyperlipidemia(P=0.001)and hypertension(P<0.001)with all-cause mortality.CONCLUSION There is an increased incidence of fibrinolysis during the pandemic period,but it has no effect on the risk of all-cause mortality.The low-and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.

Serum calcium,albumin,globulin and matrix metalloproteinase-9 levels in acute cerebral infarction patients

BACKGROUND Hemorrhagic transformation(HT)is a common complication in patients with cerebral infarction.However,its pathogenesis is poorly understood.The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy.AIM To investigate the predictive value of serum calcium,albumin,globulin and matrix metalloproteinase-9(MMP-9)levels for HT after intravenous thrombolysis(IVT)in patients with acute cerebral infarction.METHODS Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects.They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis.Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group.Serum calcium,albumin,globulin and MMP-9 levels were compared between the two groups.Regression analysis was used to discuss the relationship between these indices and HT.RESULTS The previous history of hypertension,diabetes,atrial fibrillation,cerebrovascular diseases,smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction(all P>0.05).The National Institutes of Health stroke scale(NHISS)score was associated with HT after IVT in patients with acute cerebral infarction(P<0.05).The serum calcium and albumin levels were lower in the observation group than in the control group(all P<0.05).The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group(all P<0.05).Logistic regression analysis showed that NHISS score,serum calcium,albumin,globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction(P<0.05).CONCLUSION Serum calcium,albumin,globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction.Moreover,NHISS score can be used as a predictor of post-thrombolytic HT.

Nano-Medicine for Thrombosis:A Precise Diagnosis and Treatment Strategy

Thrombosis is a global health issue and one of the leading factors of death.However,its diagnosis has been limited to the late stages,and its therapeutic window is too narrow to provide reasonable and effective treatment.In addition,clinical thrombolytics suffer from a short half-life,allergic reactions,inactivation,and unwanted tissue hemorrhage.Nano-medicines have gained extensive attention in diagnosis,drug delivery,and photo/sound/magnetic-theranostics due to their convertible properties.Furthermore,diagnosis and treatment of thrombosis using nano-medicines have also been widely studied.This review summarizes the recent advances in this area,which revealed six types of nanoparticle approaches:(1)in vitro diagnostic kits using“synthetic biomarkers”;(2)in vivo imaging using nano-contrast agents;(3)targeted drug delivery systems using artificial nanoparticles;(4)microenvironment responsive drug delivery systems;(5)drug delivery systems using biological nanostructures;and(6)treatments with external irradiation.The investigations of nano-medicines are believed to be of great significance,and some of the advanced drug delivery systems show potential applications in clinical theranotics.

Operative or Interventional Treatment in Infrainguinal Bypass Occlusion:Are There Predictive Factors Affecting Outcome?

Purpose: To evaluate outcome of interventional and surcigal treatment in infrainguinal bypass occlusion and to identify predictive factors affecting therapeutic success. Material and Methods: Over a period of three years 96 patients with infrainguinal bypass occlusion were included in this retrospective study. 52 patients were treated by catheter-directed thrombolysis and 44 patients by reconstructive vascular surgery. Results: 41 grafts could be reopened in thrombolytic group (78.8%), thrombolysis failed in 11 cases (21.2%). 34 grafts were treated successfully by reconstructive vascular surgery (77.3%), 10 grafts couldn’t be reopened or reoccluded within 30 days after surcical therapy. After a median observation time of 14.7 months 30 of 48 (62.5%) bypass grafts treated with intraarterial thrombolysis and 19 of 27 (70.4%) grafts treated with thrombectomy were overall patent. Limb salvage was 81.3% in thrombolytic group and 88.8% in surgery group. No predictive factors affecting outcome could be identified in both groups except the localization of the occluded graft (above/below knee). Conclusion: Infrainguinal bypass occlusion is a serious and challenging complication in vascular surgery. Our study showed similar results for both therapeutic strategies. Despite our data was retrospective with a small number of patients the localization of the occluded graft as predictive pretherapeutic factor was significant in thrombolytic and surgery group. Based on these scientific findings we established a guideline for choice of therapeutic treatment in our institution after searching current literature.

Thrombolysis lead to better long-term outcome in Chinese stroke patients

Aim:The rate of thrombolysis in Chinese acute ischemic stroke(AIS)was low and little was known about the long-term outcome.We aimed to compare the prognosis between thrombolysis and ordinary anti-platelet strategies in AIS.Methods:Patients,who were consecutively registered in our hospital from January 2005 to June 2012,were retrospectively studied.Inclusion criteria:(1)primary diagnoses of cerebral infarction coded with implantable cardioverter defibrillator-10 I63 to I69;(2)symptoms onset to treatment time(OTT)within 6 h;(3)thrombolysis with alteplase(TROM)or ordinary anti-platelet therapy(ANTP).Exclusion criteria:(1)symptoms and signs diminished rapidly without apparent neurological deficits;(2)no visible lesions on diffusion weighted image in magnetic resonance imaging;(3)cerebral infarction caused by serious metabolic in-balance or infections.The endpoints were defined as favorable(modified Rankin Scale 0-2)or being survival.Proportions of favorable outcome or survival were estimated by Kaplan-Meier curve and Cox regression.Results:One hundred and sixty eight cases were analyzed.Ninety one were in TROM and 77 in ANTP.Male accounted for 82(48.8%)and female 86(51.2%).The median of age was 74[interquartile range(IQR)67-79],national institute of health stroke scale(NIHSS 9)(IQR 5-17)and OTT 3.9 h(IQR 3.0-4.8)respectively.The median length of follow-up was 112(IQR 63.4-163.8)weeks.By the end of December 31,2012,87 patients(51.8%)reached favorable outcome while 81(48.2%)unfavorable.Forty five(26.8%)cases deceased.Kaplan-Meier curve estimation showed a longer favorable period of time in TROM than those in ANTP(212 weeks 95%confidence interval(CI)169.5-254.5 vs.126.9 weeks 95%CI 105.2-148.6;Log-Rank test x^(2)=19.632,P=0.000),while no significance was seen in survival time(258.0 weeks 95%CI 231.5-284.5 vs.160.8 weeks 95%CI 153.0-168.5;Log-Rank test x^(2)=2.427,P=0.119).In Cox regression,thrombolysis showed an independent protective effect for longer period of favorable outcome[202 vs.151 weeks,P=0.026,heart rate(HR)1.96,95%CI 1.958-3.540]and longer survival time instead(333 vs.170 weeks,P=0.000,HR 4.322,95%CI 1.942-9.618).The estimated proportion of favorable outcome in Chinese urban AIS was about 91%for 1 year and 50%for about 3.4 years,while the estimated proportion of survival was about 98.5%for 1 year and 50%for about 5.3 years,respectively.Conclusion:Chinese urban AIS patients who underwent thrombolysis with alteplase might have a better long-term outcome than those receiving ordinary anti-platelet therapy.

Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction:A randomized non-inferiority trial

Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No.NCT02835534).