Low-Dose Alteplase During Primary Percutaneous Coronary Intervention According to Ischemic Time.
Aged
Dose-Response Relationship, Drug
Double-Blind Method
Female
Fibrinolytic Agents
/ administration & dosage
Humans
Male
Middle Aged
Myocardial Ischemia
/ diagnosis
Percutaneous Coronary Intervention
/ methods
Prospective Studies
ST Elevation Myocardial Infarction
/ diagnosis
Time Factors
Tissue Plasminogen Activator
/ administration & dosage
ST-segment elevation myocardial infarction
fibrinolysis
microvascular obstruction
myocardial hemorrhage
primary percutaneous coronary intervention
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
16
10
2019
revised:
08
01
2020
accepted:
13
01
2020
entrez:
29
3
2020
pubmed:
29
3
2020
medline:
16
12
2020
Statut:
ppublish
Résumé
Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018). In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).
Sections du résumé
BACKGROUND
Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.
OBJECTIVES
This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.
METHODS
This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).
RESULTS
Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).
CONCLUSION
In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).
Identifiants
pubmed: 32216909
pii: S0735-1097(20)30513-1
doi: 10.1016/j.jacc.2020.01.041
pmc: PMC7109518
pii:
doi:
Substances chimiques
Fibrinolytic Agents
0
Tissue Plasminogen Activator
EC 3.4.21.68
Banques de données
ClinicalTrials.gov
['NCT02257294']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1406-1421Subventions
Organisme : Medical Research Council
ID : MC_PC_12037
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15113
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/16/74/32573
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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