Dataset Information

Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.

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.

SUBMITTER: McCartney PJ

PROVIDER: S-EPMC6583564 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

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 Peter J PJ Eteiba Hany H Maznyczka Annette M AM McEntegart Margaret M Greenwood John P JP Muir Douglas F DF Chowdhary Saqib S Gershlick Anthony H AH Appleby Clare C Cotton James M JM Wragg Andrew A Curzen Nick N Oldroyd Keith G KG Lindsay Mitchell M Rocchiccioli J Paul JP Shaukat Aadil A Good Richard R Watkins Stuart S Robertson Keith K Malkin Christopher C Martin Lynn L Gillespie Lynsey L Ford Thomas J TJ Petrie Mark C MC Macfarlane Peter W PW Tait R Campbell RC Welsh Paul P Sattar Naveed N Weir Robin A RA Fox Keith A KA Ford Ian I McConnachie Alex A Berry Colin C

JAMA 20190101 1

<h4>Importance</h4>Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes.<h4>Objective</h4>To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.<h4>Design, setting, and participants</h4>Between March 17, 2016, and December 21, 2017, 440 patients presenting at 1 ...[more]

PMID: 30620371

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Project description:Background Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results A prespecified physiology substudy of the T-TIME trial. From 2016 to 2017, patients with ST-segment-elevation myocardial infarction ?6 hours from symptom onset were randomized in a double-blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2-4, and ?4 hours) were prespecified. One hundred forty-four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0-55.0), coronary flow reserve(1.4 [1.1-2.0]), and resistive reserve ratio (1.7 [1.3-2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions In ST-segment-elevation myocardial infarction with ischemic time ?6 hours, there was overall no difference in microvascular function with alteplase versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Project description:BackgroundPrimary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI.MethodsSTEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022.ResultsIn total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups.ConclusionsIn eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Project description:BackgroundMicrovascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.ObjectivesThis 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.MethodsThis 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).ResultsOverall, 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).ConclusionIn 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).

Project description:Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297 .

Dataset Information

Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.

Similar Datasets

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