Brandi Meeks

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors

BACKGROUND Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. METHODS In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. RESULTS The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. CONCLUSIONS On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy

BACKGROUND During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial.

CONTEXT The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain. OBJECTIVE To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010. INTERVENTIONS Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT). MAIN OUTCOME MEASURES Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30. RESULTS The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group and 0.1% in the standard-dose group, P = .15). CONCLUSION Low-dose compared with standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and vascular access-site complications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00790907.

Cardioverter defibrillator implantation without induction of ventricular fibrillation: A single-blind, non-inferiority, randomised controlled trial (SIMPLE)

BACKGROUND Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. METHODS In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. FINDINGS Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). INTERPRETATION Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. FUNDING Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).

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

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.

Cell adhesion peptide modification of gold-coated polyurethanes for vascular endothelial cell adhesion

Gold-coated polyurethanes were chemisorbed with three cell-adhesion peptides having an N-terminal cysteine: cys-arg-gly-asp (CRGD), cys-arg-glu-asp-val (CREDV), and the cyclic peptide cys-cys-arg-arg-gly-asp-try-leu-cys (CCRRGDWLC). The peptides were selected based on their presumed preferential interactions with the cell-surface integrins on vascular endothelial cells. The ability of the surfaces to support the preferential adhesion of human vascular endothelial cells was studied by comparing in vitro adhesion results for these cells with those from mouse 3T3 fibroblasts. Surface modification with the peptides was confirmed by water-contact angles and XPS. Surface morphology was determined by AFM and SEM. In vitro cell-culture studies in conjunction with plasma-protein adsorption and immunoblotting were performed on the various modified surfaces. The data suggest that peptide-modified surfaces have significant potential for supporting cell adhesion. Little or no cell adhesion was noted on gold- or cysteine-modified control surfaces. Human vascular endothelial cells showed the greatest adhesion to the CCRRGDWLC-modified surfaces, and the 3T3 fibroblasts adhered best to the CREDV-modified surfaces. Protein adsorption studies suggest that the preferential adsorption of the cell-adhesive proteins fibronectin and vitronectin is not likely mediating the differences noted. It is concluded that the cell-adhesive peptide-modified gold-coated polymers have significant potential for further development both as model substrates for fundamental studies and for use in biomaterials applications.

Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction.

AIMS TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings. METHODS AND RESULTS A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00). CONCLUSION Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy.

Design and rationale of the TOTAL trial: A randomized trial of routine aspiration ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in patients with ST-elevation myocardial infarction undergoing primary PCI

BACKGROUND A major limitation of primary percutaneous coronary intervention (PPCI) for the treatment of ST-elevation myocardial infarction (STEMI) is impaired microvascular perfusion due to embolization and obstruction of microcirculation with thrombus. Manual thrombectomy has the potential to reduce distal embolization and improve microvascular perfusion. Clinical trials have shown mixed results regarding thrombectomy. OBJECTIVE The objective of this study is to evaluate the efficacy of routine upfront manual aspiration thrombectomy during PPCI compared with percutaneous coronary intervention alone in patients with STEMI. DESIGN This is a multicenter, prospective, open, international, randomized trial with blinded assessment of outcomes. Patients with STEMI undergoing PPCI are randomized to upfront routine manual aspiration thrombectomy with the Export catheter (Medtronic CardioVascular, Santa Rosa, CA) or to percutaneous coronary intervention alone. The primary outcome is the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening New York Heart Association class IV heart failure up to 180 days. The trial uses an event-driven design and will recruit 10,700 patients. SUMMARY The TOTAL trial will determine the effect of routine manual aspiration thrombectomy during PPCI on clinically important outcomes.

Culprit lesion thrombus burden after manual thrombectomy or percutaneous coronary intervention-alone in ST-segment elevation myocardial infarction: the optical coherence tomography sub-study of the TOTAL (ThrOmbecTomy versus PCI ALone) trial

AIMS Manual thrombectomy has been proposed as a strategy to reduce thrombus burden during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the effectiveness of manual thrombectomy in reducing thrombus burden is uncertain. In this substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial, we compared the thrombus burden at the culprit lesion using optical coherence tomography (OCT) in patients treated with thrombectomy vs. PCI-alone. METHODS AND RESULTS The TOTAL trial (N = 10 732) was an international, multicentre, randomized trial of thrombectomy (using the Export catheter, Medtronic Cardiovascular, Santa Rosa, CA, USA) in STEMI patients treated with primary PCI. The OCT substudy prospectively enrolled 214 patients from 13 sites in 5 countries. Optical coherence tomography was performed immediately after thrombectomy or PCI-alone and then repeated after stent deployment. Thrombus quantification was performed by an independent core laboratory blinded to treatment assignment. The primary outcome of pre-stent thrombus burden as a percentage of segment analysed was 2.36% (95% CI: 1.73-3.22) in the thrombectomy group and 2.88% (95% CI: 2.12-3.90) in the PCI-alone group (P = 0.373). Absolute pre-stent thrombus volume was not different (2.99 vs. 3.74 mm(3), P = 0.329). Other secondary outcomes of pre-stent quadrants of thrombus, post-stent atherothrombotic burden, and post-stent atherothrombotic volume were not different between groups. CONCLUSION Manual thrombectomy did not reduce pre-stent thrombus burden at the culprit lesion compared with PCI-alone. Both strategies were associated with low thrombus burden at the lesion site after the initial intervention to restore flow.

Thrombus Aspiration in ST Elevation Myocardial Infarction : An Individual Patient Meta-analysis

Background: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment–elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment–elevation myocardial infarction. Methods: Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment–elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. Results: The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70–1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98–2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65–0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02–2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. Conclusions: Routine thrombus aspiration during PCI for ST-segment–elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. Clinical Trial Registration: URLs: http://www.ClinicalTrials.gov http://www.crd.york.ac.uk/prospero/. Unique identifiers: NCT02552407 and CRD42015025936.Background: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment–elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment–elevation myocardial infarction. Methods: Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment–elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. Results: The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70–1.01; P =0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98–2.10; P =0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65–0.98; P =0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02–2.42, P =0.04). However, the interaction P values were 0.32 and 0.34, respectively. Conclusions: Routine thrombus aspiration during PCI for ST-segment–elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. Clinical Trial Registration: URLs: . Unique identifiers: [NCT02552407][1] and CRD42015025936. # Clinical Perspective {#article-title-14} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02552407&atom=%2Fcirculationaha%2F135%2F2%2F143.atomBACKGROUND—: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with STEMI. METHODS—: Included were large (N≥1000) randomized controlled trials comparing manual thrombectomy vs. PCI alone in patients with STEMI. Individual patient data was provided by the leadership of each trial. The pre-specified primary efficacy outcome was cardiovascular (CV) mortality within 30 days and the primary safety outcome was stroke or transient ischemic attack (TIA) within 30 days. RESULTS—: The 3 eligible randomized trials (TAPAS, TASTE and TOTAL) enrolled 19,047 patients, of whom 18,306 underwent PCI and were included in the primary analysis. CV death at 30 days occurred in 221 (2.4%) of 9155 patients randomized to thrombus aspiration and 262 (2.9%) of 9151 randomized to PCI alone (hazard ratio (HR) 0.84; 95% CI 0.70-1.01, p=0.06). Stroke or TIA occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio [OR] 1.43 95% CI 0.98-2.1, p=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure or target vessel revascularization. In the subgroup with high thrombus burden (TIMI thrombus grade ≥3) thrombus aspiration was associated with less CV death (170 [2.5%] vs. 205 [3.1%] HR 0.80; 95% CI 0.65-0.98, p =0.03), and with more stroke or TIA (55 [0.9%] vs. 34 [0.5%] OR 1.56; 95% CI 1.02-2.42, p=0.04). However, the interaction p-values were 0.32 and 0.34, respectively. CONCLUSIONS—: Routine thrombus aspiration during STEMI PCI did not improve clinical outcomes. In the high thrombus burden subgroup the trends toward reduced CV death and increased stroke or TIA provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. CLINICAL TRIAL REGISTRATION—: ClinicalTrials.gov identifier NCT02552407, PROSPERO CRD42015025936 (Less)