Clinical impact of direct stenting and interaction with thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: Thrombectomy Trialists Collaboration.

Aims: Preliminary studies suggest that direct stenting (DS) during percutaneous coronary intervention (PCI) may reduce microvascular obstruction and improve clinical outcome. Thrombus aspiration may facilitate DS. We assessed the impact of DS on clinical outcome and myocardial reperfusion and its interaction with thrombus aspiration among ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI. Methods and results: Patient-level data from the three largest randomized trials on routine manual thrombus aspiration vs. PCI only were merged. A 1:1 propensity matched population was created to compare DS and conventional stenting. Synergy between DS and thrombus aspiration was assessed with interaction P-values in the final models. In the unmatched population (n = 17 329), 32% underwent DS and 68% underwent conventional stenting. Direct stenting rates were higher in patients randomized to thrombus aspiration as compared with PCI only (41% vs. 22%; P < 0.001). Patients undergoing DS required less contrast (162 mL vs. 172 mL; P < 0.001) and had shorter fluoroscopy time (11.1 min vs. 13.3 min; P < 0.001). After propensity matching (n = 10 944), no significant differences were seen between DS and conventional stenting with respect to 30-day cardiovascular death [1.7% vs. 1.9%; hazard ratio 0.88, 95% confidence interval (CI) 0.55-1.41; P = 0.60; Pinteraction = 0.96) and 30-day stroke or transient ischaemic attack (0.6% vs. 0.4%; odds ratio 1.02; 95% CI 0.14-7.54; P = 0.99; Pinteraction = 0.81). One-year results were similar. No significant differences were seen in electrocardiographic and angiographic myocardial reperfusion measures. Conclusion: Direct stenting rates were higher in patients randomized to thrombus aspiration. Clinical outcomes and myocardial reperfusion measures did not differ significantly between DS and conventional stenting and there was no interaction with thrombus aspiration.

Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

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.

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.

No-reflow after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: an angiographic core laboratory analysis of the TOTAL Trial.

BACKGROUND: The optimal strategy to prevent no-reflow in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) is unknown. AIMS: We aimed to examine the effect of thrombectomy on the outcome of no-reflow in key subgroups and the adverse clinical outcomes associated with no-reflow. METHODS: We performed a post hoc analysis of the TOTAL Trial, a randomised trial of 10,732 patients comparing thrombectomy versus PCI alone. This analysis utilised the angiographic data of 1,800 randomly selected patients. RESULTS: No-reflow was diagnosed in 196 of 1,800 eligible patients (10.9%). No-reflow occurred in 95/891 (10.7%) patients randomised to thrombectomy compared with 101/909 (11.1%) in the PCI-alone arm (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.71-1.28; p-value=0.76). In the subgroup of patients who underwent direct stenting, those randomised to thrombectomy compared with PCI alone experienced less no-reflow (19/371 [5.1%] vs 21/216 [9.7%], OR 0.50, 95% CI: 0.26-0.96). In patients who did not undergo direct stenting, there was no difference between the groups (64/504 [12.7%] vs 75/686 [10.9%)], OR 1.18, 95% CI: 0.82-1.69; interaction p-value=0.02). No-reflow patients had a significantly increased risk of experiencing the primary composite outcome (cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA Class IV heart failure) at 1 year (adjusted hazard ratio 1.70, 95% CI: 1.13-2.56; p-value=0.01). CONCLUSIONS: In patients with STEMI treated by PCI, thrombectomy did not reduce no-reflow in all patients but may be synergistic with direct stenting. No-reflow is associated with increased adverse clinical outcomes.

Lack of consistency in the relationship between asymptomatic DVT detected by venography and symptomatic VTE in thromboprophylaxis trials.

Asymptomatic deep-vein thrombosis (DVT) detected by mandatory venography, a surrogate outcome, comprises most of the efficacy outcome events in recent thromboprophylaxis trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in these clinical trials requires a consistent relationship between asymptomatic DVT and symptomatic venous thromboembolism (VTE). In this systematic review of high quality VTE prevention trials, we examined the consistency of the ratios of asymptomatic DVT to symptomatic VTE across a broad range of indications. Studies were identified from citations listed in the chapters on VTE prevention in the antithrombotic guidelines by the American College of Chest Physicians, 2012. A study was eligible if it: 1) was a randomised trial comparing an anticoagulant with standard of care; 2) included at least 500 participants; 3) reported asymptomatic or all DVT rates; and 4) reported symptomatic VTE rates. Of the 26 eligible trials, 19 trials were conducted in orthopaedic patients, five in general surgery patients and two in general medical patients. The overall median rates (ranges) for asymptomatic DVT and symptomatic VTE were 9.11 % (0.75 to 54.87 %) and 0.49 % (0.00 to 3.10 %), respectively. The median ratio was 14.53, with a wide range (2.75 to 103.86). Wide variability in the ratios persisted despite indication- and anticoagulant-specific analyses. In VTE prevention trials of alternative anticoagulants, the wide variability in the ratios of asymptomatic DVT to symptomatic VTE precludes judging the trade-off between thrombotic and bleeding events on the basis of composite outcomes dominated by venographic DVT.

Randomized Controlled Trial of Radiation Protection With a Patient Lead Shield and a Novel, Nonlead Surgical Cap for Operators Performing Coronary Angiography or Intervention.

BACKGROUND: Interventional cardiologists receive one of the highest levels of annual occupational radiation exposure. Further measures to protect healthcare workers are needed. METHODS AND RESULTS: We evaluated the efficacy of a pelvic lead shield and a novel surgical cap in reducing operators' radiation exposure. Patients undergoing coronary angiography or percutaneous coronary intervention (n=230) were randomized to have their procedure with or without a lead shield (Ultraray Medical, Oakville, Canada) placed over the patient. During all procedures, operators wore the No Brainer surgical cap (Worldwide Innovations and Technology, Kansas City, KS) designed to protect the head from radiation exposure. The coprimary outcomes for the lead shield comparison were (1) operator dose (µSv) and (2) operator dose indexed for air kerma (µSv/mGy). For the cap comparison, the primary outcome was the difference between total radiation dose (µSv; internal and external to cap). The lead shield use resulted in a 76% reduction in operator dose (mean dose, 3.07; 95% confidence interval [CI], 2.00-4.71 µSv lead shield group versus 12.57; 95% CI, 8.14-19.40 µSv control group; P<0.001). The mean dose indexed for air kerma was reduced by 72% (0.004; 95% CI, 0.003-0.005 µSv/mGy lead shield group versus 0.015; 95% CI, 0.012-0.019 µSv/mGy control group; P<0.001). The cap use resulted in a significant reduction in operator head radiation exposure (mean left temporal difference [external-internal] radiation dose was 4.79 [95% CI, 3.30-6.68] µSv; P<0.001). CONCLUSIONS: The use of a pelvic lead shield and the cap reduced significantly the operator radiation exposure and can be easily incorporated into clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02128035.

Performance of the high-sensitivity troponin assay in diagnosing acute myocardial infarction: systematic review and meta-analysis.

BACKGROUND: High-sensitivity cardiac troponin assays have been adopted by many clinical centres worldwide; however, clinicians are uncertain how to interpret the results. We sought to assess the utility of these assays in diagnosing acute myocardial infarction (MI). METHODS: We carried out a systematic review and meta-analysis of studies comparing high-sensitivity with conventional assays of cardiac troponin levels among adults with suspected acute MI in the emergency department. We searched MEDLINE, EMBASE and Cochrane databases up to April 2013 and used bivariable random-effects modelling to obtain summary parameters for diagnostic accuracy. RESULTS: We identified 9 studies that assessed the use of high-sensitivity troponin T assays (n = 9186 patients). The summary sensitivity of these tests in diagnosing acute MI at presentation to the emergency department was estimated to be 0.94 (95% confidence interval [CI] 0.89-0.97); for conventional tests, it was 0.72 (95% CI 0.63-0.79). The summary specificity was 0.73 (95% CI 0.64-0.81) for the high-sensitivity assay compared with 0.95 (95% CI 0.93-0.97) for the conventional assay. The differences in estimates of the summary sensitivity and specificity between the high-sensitivity and conventional assays were statistically significant (p < 0.01). The area under the curve was similar for both tests carried out 3-6 hours after presentation. Three studies assessed the use of high-sensitivity troponin I assays and showed similar results. INTERPRETATION: Used at presentation to the emergency department, the high-sensitivity cardiac troponin assay has improved sensitivity, but reduced specificity, compared with the conventional troponin assay. With repeated measurements over 6 hours, the area under the curve is similar for both tests, indicating that the major advantage of the high-sensitivity test is early diagnosis.

Everolimus-Eluting versus Paclitaxel-Eluting Stents in Percutaneous Coronary Intervention: Meta-Analysis of Randomized Trials.

Background. Individual randomized trials have suggested that everolimus-eluting stents may have improved clinical outcomes compared to paclitaxel-eluting stents, but individual trials are underpowered to examine outcomes such as mortality and very late stent thrombosis. Methods. Medline, Cochrane, and conference proceedings were searched for randomized trials comparing everolimus versus paclitaxel-eluting stents for percutaneous coronary intervention. Results. 6792 patients were included from 4 randomized controlled trials. Stent thrombosis was reduced with everolimus stents versus paclitaxel stents (0.7% versus 2.3%; OR: 0.32; CI: 0.20-0.51; P < 0.00001). The reductions in stent thrombosis were observed in (i) early stent thrombosis (within 30 days) (0.2% versus 0.9%; OR: 0.24; P = 0.0005), (ii) late (day 31-365) (0.2% versus 0.6%; OR: 0.32; P = 0.01), and (iii) very late stent thrombosis (>365 days) (0.2% versus 0.8%; OR: 0.34; P = 0.009). The rates of cardiovascular mortality were 1.2% in everolimus group and 1.6% in paclitaxel group (OR: 0.85; P = 0.43). Patients receiving everolimus-eluting stents had significantly lower myocardial infarction events and target vessel revascularization as compared to paclitaxel-eluting stents. Interpretation. Everolimus compared to paclitaxel-eluting stents reduced the incidence of early, late, and very late stent thrombosis as well as target vessel revascularization.

Left main thrombus as a complication of thrombectomy during primary percutaneous coronary intervention.

Small randomized trials in patients with ST-elevation myocardial infarction have shown that aspiration thrombectomy improves angiographic outcomes and may improve clinical outcomes. However, there remains a lack of reports on device-related complications. We report a case of a device complication involving the left main coronary artery where a large burden of thrombus was brought back into the left main coronary artery from the circumflex during aspiration thrombectomy.