Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction.The purpose of this open-label,randomized,multi-center,ang...Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction.The purpose of this open-label,randomized,multi-center,angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction.Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October,2002 to March,2004,in 5 hospitals in Beijing.After giving informed consent,patients were randomly assigned a single-bolus injection of tenecteplase(30-50 mg according to body weight)or front loaded alteplase(100 mg),and underwent coronary angiography at 90 min after starting the study drug.All patients received aspirin and heparin(target activated partial thromboplastin time 50-70 s).The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes.Other efficacy end points included TIMI grade 2/3 flow at 90 minutes.Safety end points included all stroke,intracranial hemorrhage(ICH),moderate/severe hemorrhage(except for ICH),all-cause mortality at 30-days,and major non-fatal cardiac events at 30 days.Results Overall 110 patients were eligible for statistical analysis,with 58 patients assigned to receive tenecteplase and 52 patients to alteplase.Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%)similar to that of alteplase(66.7%,P=1.0);the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase(89.5%versus 80.4%,respectively,P=0.278).At 30 days,rates for all strokes were similar for the two groups(5.17%for tenecteplase and 1.92%for alteplase,P=0.62);rates of ICH were 3.45%and 1.92%(tenecteplase and rt-PA,P=1.00)respectively.The rate of moderate/severe hemorrhage was 8.62%with tenecteplase and 5.77%with alteplase(P=0.72);total mortality was almost identical in the two groups(13.8%versus 9.6%,respectively,P=0.565)while the rates of non-fatal cardiac complications were 10.35%and 11.54%(tenecteplase and alteplase,P=1.0).Conclusions The efficacy of a single-bolus,weight-adjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow,and TIMI 2 or 3 flow,but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China.These negative safety results might be due to the high rate of percutaneous coronary intervention(PCI)and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization,so further studies are needed to confirm the safety for tenecteplase in Chinese patients.展开更多
Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its...Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.展开更多
Background Despite successful reperfusion after thrombectomy for large vessel occlusion(LVO)stroke,up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safet...Background Despite successful reperfusion after thrombectomy for large vessel occlusion(LVO)stroke,up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial(IA)tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3.Methods ANGEL-TNK is a multicentre,open-label,assessor-blinded endpoint,prospective randomised,controlled trial that will enrol up to 256 patients.Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio.Results The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale(mRS)0–1.The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation.Secondary endpoints include 90-day ordinal mRS,mRS 0–2,mRS 0–3,all-cause mortality and any intracranial haemorrhage.Conclusion In patients with anterior circulation LVO stroke,the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes.Trial registration number NCT05624190.展开更多
Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with altepl...Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.展开更多
BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-el...BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction(STEMI)thrombolysis in an Asian population.METHODS:This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital.Total population sampling was used in this study.The primary outcome was bleeding events post-thrombolysis,categorised using the Thrombolysis in Myocardial Infarction(TIMI)bleeding criteria.Inferential statistics were used to determine the associations between relevant variables.RESULTS:Data from 941 patients were analysed.A total of 156(16.6%)STEMI patients bled post-thrombolysis.Major,minor,and minimal TIMI occurred in 7(0.7%),17(1.8%),and 132(14.0%)patients,respectively.Age 65 years(P=0.031)and Malaysian Chinese(P=0.008)were associated with a higher incidence of bleeding post-thrombolysis.Conversely,foreigners(P=0.032)and current smoker(P=0.007)were associated with a lower incidence of bleeding.Both TIMI major(P<0.001)and TIMI minor(P<0.001)were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients.TIMI minor bleeding was significantly higher in the streptokinase recipients.The bleeding sites were comparable between streptokinase and tenecteplase recipients,except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients(P=0.027).CONCLUSION:In our Asian population,the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported.The development of TIMI major and minor bleeding complications is associated with higher mortality.展开更多
文摘Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction.The purpose of this open-label,randomized,multi-center,angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction.Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October,2002 to March,2004,in 5 hospitals in Beijing.After giving informed consent,patients were randomly assigned a single-bolus injection of tenecteplase(30-50 mg according to body weight)or front loaded alteplase(100 mg),and underwent coronary angiography at 90 min after starting the study drug.All patients received aspirin and heparin(target activated partial thromboplastin time 50-70 s).The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes.Other efficacy end points included TIMI grade 2/3 flow at 90 minutes.Safety end points included all stroke,intracranial hemorrhage(ICH),moderate/severe hemorrhage(except for ICH),all-cause mortality at 30-days,and major non-fatal cardiac events at 30 days.Results Overall 110 patients were eligible for statistical analysis,with 58 patients assigned to receive tenecteplase and 52 patients to alteplase.Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%)similar to that of alteplase(66.7%,P=1.0);the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase(89.5%versus 80.4%,respectively,P=0.278).At 30 days,rates for all strokes were similar for the two groups(5.17%for tenecteplase and 1.92%for alteplase,P=0.62);rates of ICH were 3.45%and 1.92%(tenecteplase and rt-PA,P=1.00)respectively.The rate of moderate/severe hemorrhage was 8.62%with tenecteplase and 5.77%with alteplase(P=0.72);total mortality was almost identical in the two groups(13.8%versus 9.6%,respectively,P=0.565)while the rates of non-fatal cardiac complications were 10.35%and 11.54%(tenecteplase and alteplase,P=1.0).Conclusions The efficacy of a single-bolus,weight-adjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow,and TIMI 2 or 3 flow,but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China.These negative safety results might be due to the high rate of percutaneous coronary intervention(PCI)and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization,so further studies are needed to confirm the safety for tenecteplase in Chinese patients.
基金National Natural Science Foundation of China(82271352)the Science and Technology Commission of Shanghai Municipality(20Z11900802)the Shanghai Municipal Health Commission(2022XD022).
文摘Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.
文摘Background Despite successful reperfusion after thrombectomy for large vessel occlusion(LVO)stroke,up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial(IA)tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3.Methods ANGEL-TNK is a multicentre,open-label,assessor-blinded endpoint,prospective randomised,controlled trial that will enrol up to 256 patients.Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio.Results The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale(mRS)0–1.The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation.Secondary endpoints include 90-day ordinal mRS,mRS 0–2,mRS 0–3,all-cause mortality and any intracranial haemorrhage.Conclusion In patients with anterior circulation LVO stroke,the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes.Trial registration number NCT05624190.
基金funded by Beijing Municipal Science&Technology Committee(Z211100003521019)China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical(Guangzhou)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)National Natural Science Foundation(82111530203,82171272).
文摘Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.
文摘BACKGROUND:Bleeding outcomes are crucial primary safety endpoints in studies involving thrombolytic agents.This study aimed to determine the incidence,characteristics and mortality outcomes of bleeding following ST-elevation myocardial infarction(STEMI)thrombolysis in an Asian population.METHODS:This single-centre retrospective study included all STEMI patients who received thrombolytic therapy from 2016 to 2020 in a Malaysian tertiary hospital.Total population sampling was used in this study.The primary outcome was bleeding events post-thrombolysis,categorised using the Thrombolysis in Myocardial Infarction(TIMI)bleeding criteria.Inferential statistics were used to determine the associations between relevant variables.RESULTS:Data from 941 patients were analysed.A total of 156(16.6%)STEMI patients bled post-thrombolysis.Major,minor,and minimal TIMI occurred in 7(0.7%),17(1.8%),and 132(14.0%)patients,respectively.Age 65 years(P=0.031)and Malaysian Chinese(P=0.008)were associated with a higher incidence of bleeding post-thrombolysis.Conversely,foreigners(P=0.032)and current smoker(P=0.007)were associated with a lower incidence of bleeding.Both TIMI major(P<0.001)and TIMI minor(P<0.001)were associated with a higher incidence of all-cause in-hospital mortality among STEMI patients.TIMI minor bleeding was significantly higher in the streptokinase recipients.The bleeding sites were comparable between streptokinase and tenecteplase recipients,except for a significantly higher incidence of gastrointestinal bleeding in the streptokinase recipients(P=0.027).CONCLUSION:In our Asian population,the incidence of total bleeding events following STEMI thrombolysis is comparable to that previously reported.The development of TIMI major and minor bleeding complications is associated with higher mortality.
