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- Title
Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.
- Authors
McCartney, Peter J.; Eteiba, Hany; Maznyczka, Annette M.; McEntegart, Margaret; Greenwood, John P.; Muir, Douglas F.; Chowdhary, Saqib; Gershlick, Anthony H.; Appleby, Clare; Cotton, James M.; Wragg, Andrew; Curzen, Nick; Oldroyd, Keith G.; Lindsay, Mitchell; Rocchiccioli, J. Paul; Shaukat, Aadil; Good, Richard; Watkins, Stuart; Robertson, Keith; Malkin, Christopher
- Abstract
<bold>Importance: </bold>Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes.<bold>Objective: </bold>To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.<bold>Design, Setting, and Participants: </bold>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.<bold>Interventions: </bold>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.<bold>Main Outcomes and Measures: </bold>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.<bold>Results: </bold>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.<bold>Conclusions and Relevance: </bold>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.<bold>Trial Registration: </bold>ClinicalTrials.gov Identifier: NCT02257294.
- Subjects
ALTEPLASE; MYOCARDIAL infarction; DRUG side effects; MYOCARDIAL reperfusion; SURGICAL stents; MAGNETIC resonance imaging; CORONARY heart disease surgery; CARDIOVASCULAR system; COMBINED modality therapy; COMPARATIVE studies; CORONARY arteries; CORONARY disease; DOSE-effect relationship in pharmacology; RESEARCH methodology; MEDICAL care; MEDICAL cooperation; PHARMACOKINETICS; QUALITY of life; RESEARCH; RESEARCH funding; TISSUE plasminogen activator; EVALUATION research; RANDOMIZED controlled trials; TREATMENT effectiveness; VASCULAR catheters; TROPONIN; CORONARY angiography; INTRA-arterial infusions
- Publication
JAMA: Journal of the American Medical Association, 2019, Vol 321, Issue 1, p56
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.2018.19802