Elsevier

The Lancet

Volume 387, Issue 10014, 9–15 January 2016, Pages 127-135
The Lancet

Articles
Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

https://doi.org/10.1016/S0140-6736(15)00448-1Get rights and content

Summary

Background

Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice.

Methods

The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044.

Findings

Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10 064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87–1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76–1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10–2·51], p=0·015).

Interpretation

Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI.

Funding

Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.

Introduction

One of the hallmarks of ST elevation myocardial infarction (STEMI) is occlusion of the infarct vessel with a thrombus. Rapid primary percutaneous coronary intervention (PCI) has been shown to be beneficial in patients with STEMI.1 However, a limitation of this intervention is distal embolisation of the thrombus after balloon dilatation or stenting, which can obstruct the distal microvasculature and impair tissue perfusion.2 Both distal embolisation and reduced tissue perfusion (impaired ST segment resolution and angiographic myocardial blush grade) after primary PCI have been associated with substantial increases in mortality and morbidity.2, 3, 4

Thrombus aspiration during primary PCI has been thought to be an effective method for reducing distal embolisation and improving microvascular perfusion. The Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS),5 which enrolled 1071 patients, showed that routine thrombus aspiration improved the primary outcome of microvascular perfusion. At long-term follow-up at 1 year, the TAPAS trial also showed a significant reduction in mortality that was not apparent at 30 days.6 By contrast, the larger Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial7, 8 of 7244 patients showed no significant reduction in mortality either at 30 days or at 1 year.

Research in context

Evidence before this study

We did a comprehensive systematic search of the MEDLINE, Embase, and Cochrane databases for randomised controlled trials that assessed the clinical utility of manual thrombectomy in patients presenting with ST elevation myocardial infarction (STEMI) only, published from any time up to Sept 3, 2015. We did not use any language restrictions in our search. Our search terms included “thrombectomy”, “thrombus aspiration”, “thromboaspiration”, “myocardial infarction”, “percutaneous coronary intervention”, and “randomized” (appendix p 10). We identified 669 abstracts, from which we selected 20 randomised trials (n=21 173) for inclusion. Our search showed that before the TOTAL and TASTE trials were done, trials of manual thrombectomy were powered for surrogate outcomes and were quite small.

Added value of this study

TOTAL is the largest randomised trial so far to compare routine manual thrombectomy to PCI alone during STEMI PCI.

Implications of all the available evidence

In an updated meta-analysis, manual thrombectomy did not reduce all-cause mortality or recurrent myocardial infarction but was associated with an increased risk of stroke. Consequently, manual thrombectomy can no longer be recommended as a routine strategy during PCI for STEMI.

The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) 9 showed no difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or class IV heart failure between patients who had received thrombectomy with PCI versus those who had PCI alone. Notably, the trial showed significant improvements in surrogate outcomes of distal embolisation and ST segment resolution in patients who received thrombectomy. However, whether or not the benefits of these surrogate outcomes will translate into a longer term clinical benefit at 1 year remains unclear. To address this unresolved question, we did a follow-up analysis of the 1-year outcomes of the TOTAL study.

Section snippets

Study design and participants

The design of the TOTAL trial has been previously described.10 TOTAL was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy with the Export catheter (Medtronic Inc, Santa Rosa, CA, USA) with PCI versus PCI alone in patients with STEMI. The study was done in 87 hospitals in 20 countries (appendix p 3). An independent data and safety monitoring committee monitored the safety of the trial. The Population Health Research Institute at McMaster University

Results

Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled from 87 hospitals in 20 countries, of whom 5372 were randomly assigned to thrombectomy followed by PCI and 5360 were assigned to PCI alone (figure 1). Of these patients, 10 064 (94%) underwent primary PCI for (index) STEMI. Bailout thrombectomy after a failure of the PCI alone strategy was done in 354 (7%) of 5029 patients randomly assigned to PCI alone (figure 1).

Thrombectomy was attempted in 4804 (95%) of 5035

Discussion

The TOTAL trial is the largest trial so far to compare a strategy of routine thrombus aspiration and PCI versus PCI alone in patients with STEMI. Despite the early improvement in surrogate outcomes such as ST segment resolution, routine thrombus aspiration did not reduce the incidence of cardiovascular death, myocardial infarction, shock, or heart failure at 1 year. Moreover, routine thrombus aspiration was associated with a potentially increased rate of stroke. Additionally, the results showed

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