Effect of low-dose intracoronary alteplase during primary percutaneous coronary intervention on microvascular obstruction in patients with acute myocardial infarction: a randomized clinical trial

McCartney, P. J. et al. (2019) Effect of low-dose intracoronary alteplase during primary percutaneous coronary intervention on microvascular obstruction in patients with acute myocardial infarction: a randomized clinical trial. JAMA: Journal of the American Medical Association, 321(1), pp. 56-68. (doi:10.1001/jama.2018.19802) (PMID:30620371)

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Abstract

Importance: Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes. Objective: To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction. Design, Setting, and Participants: Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the United Kingdom within 6 hours of STEMI due to a proximal–mid-vessel occlusion of a major coronary artery were randomized in a 1:1:1 dose-ranging trial design. Patient follow-up to 3 months was completed on April 12, 2018. Interventions: Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145) by manual infusion over 5 to 10 minutes. The intervention was scheduled to occur early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery and before stent implant. Main Outcomes and Measures: The primary outcome was the amount of microvascular obstruction (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment. The primary comparison was the alteplase 20-mg group vs the placebo group; if not significant, the alteplase 10-mg group vs the placebo group was considered a secondary analysis. Results: Recruitment stopped on December 21, 2017, because conditional power for the primary outcome based on a prespecified analysis of the first 267 randomized participants was less than 30% in both treatment groups (futility criterion). Among the 440 patients randomized (mean age, 60.5 years; 15% women), the primary end point was achieved in 396 patients (90%), 17 (3.9%) withdrew, and all others were followed up to 3 months. In the primary analysis, the mean microvascular obstruction did not differ between the 20-mg alteplase and placebo groups (3.5% vs 2.3%; estimated difference, 1.16%; 95% CI, −0.08% to 2.41%; P = .32) nor in the analysis of 10-mg alteplase vs placebo groups (2.6% vs 2.3%; estimated difference, 0.29%; 95% CI, −0.76% to 1.35%; P = .74). Major adverse cardiac events (cardiac death, nonfatal MI, unplanned hospitalization for heart failure) occurred in 15 patients (10.1%) in the placebo group, 18 (12.9%) in the 10-mg alteplase group, and 12 (8.2%) in the 20-mg alteplase group. Conclusions and Relevance: Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction. The study findings do not support this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02257294

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and McConnachie, Dr Alex and Robertson, Dr Keith and Shaukat, Dr Aadil and Rocchiccioli, Dr John and Welsh, Dr Paul and Petrie, Professor Mark and Gillespie, Dr Lynsey and Mccartney, Dr Peter and Oldroyd, Dr Keith and Ford, Professor Ian and Berry, Professor Colin and Maznyczka, Dr Annette Marie and Eteiba, Dr Hany and Tait, Dr Robert and Sattar, Professor Naveed and Ford, Mr Thomas
Authors: McCartney, P. J., Eteiba, H., Maznyczka, A. M., McEntegart, M., Greenwood, J. P., Muir, D. F., Chowdhary, S., Gershlick, A. H., Appleby, C., Cotton, J. M., Wragg, A., Curzen, N., Oldroyd, K. G., Lindsay, M., Rocchiccioli, J. P., Shaukat, A., Good, R., Watkins, S., Robertson, K., Malkin, C., Martin, L., Gillespie, L., Ford, T. J., Petrie, M. C., Macfarlane, P. W., Tait, R. C., Welsh, P., Sattar, N., Weir, R. A., Fox, K. A., Ford, I., McConnachie, A., and Berry, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:JAMA: Journal of the American Medical Association
Publisher:American Medical Association
ISSN:0098-7484
ISSN (Online):1538-3598

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
622521A randomised parallel group double blind placebo-controlled trial of low dose adjunctive alteplase during primary PCI (T-TIME)Colin BerryNational Institute for Health Research (NIHR)12/170/45RI CARDIOVASCULAR & MEDICAL SCIENCES
744211T-TIME Coronary Physiology StudyColin BerryBritish Heart Foundation (BHF)FS/16/74/32573RI CARDIOVASCULAR & MEDICAL SCIENCES