The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear.
One month after they had undergone ...implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.
Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval CI, -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority).
One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).
Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome.
We randomly ...assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events.
The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval CI, 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34).
In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).
Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a ...randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov , number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio RR 0·85, 95% CI 0·74–0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73–0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49–0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53–0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo.
Purpose
To investigate the association of the degree of stent expansion, as assessed by optical coherence tomography (OCT), following stent implantation, and clinical outcomes in ST-segment elevation ...myocardial infarction (STEMI) patients.
Methods
STEMI patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study were selected; Clinical outcomes were collected through 1 year. Stent expansion index is a minimum stent area (MSA) divided by average lumen area (average of proximal and distal reference lumen area). The following variables were measured: MSA (< 4.5mm
2
), dissection (> 200 µm in width and < 5 mm from stent segment), malapposition (> 200 µm distance of stent from vessel wall), a thrombus (area > 5% of lumen area) were compared.
Results
A total of 151 patients were included; after excluding patients with suboptimal OCT quality, the population with available OCT was classified into 2 groups: under–expanded < 90% (N = 72, 51%) and well–expanded ≥ 90% (N = 67, 49%). In the well–expanded group, a significant number of the proximal vessels had a lumen area < 4.5mm
2
(16.1%, p < 0.001) and a greater thrombus burden within stent (56.7%, p = 0.042). The overall 30 day and 1 year major adverse cardiovascular event (MACE) rates were 5% and 6.1%, respectively.
Conclusion
Irrespective of the degree of stent expansion, the OCT findings, in STEMI patients, and the MACE at 30 days and one year follow up was low; further, well–expanded stents led to a more significant residual thrombotic burden within the stent but seemed to have insignificant clinical impact. Acknowledged stent optimization criteria, traditionally related to worse outcomes in stable patients, do not seem to be associated with worse outcomes in this STEMI population.
The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other ...vascular biomarkers, including systemic adenosine plasma levels.
The in vivo off-target effects of ticagrelor in post–acute coronary syndrome (ACS) patients remain poorly characterized.
Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation.
Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel.
Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans HI-TECH; NCT02587260).
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AbstractBackgroundThe twelve‑lead electrocardiogram (ECG) has become an essential tool for the diagnosis, risk stratification, and management of patients with acute coronary syndromes (ACS). However, ...several areas of residual controversies or gaps in evidence exist. Among them, P-wave abnormalities identifying atrial ischemia/infarction are largely neglected in clinical practice, and their diagnostic and prognostic implications remain elusive; the value of ECG to identify the culprit lesion has been investigated, but validated criteria indicating the presence of coronary occlusion in patients without ST-elevation are lacking; finally, which criteria among the multiple proposed, better define pathological Q-waves or success of revascularisation deserve further investigations. MethodsThe Minimizing Adverse hemorrhagic events via TRansradial access site and systemic Implementation of AngioX (MATRIX) trial was designed to test the impact of bleeding avoidance strategies on ischemic and bleeding outcomes across the whole spectrum of patients with ACS receiving invasive management. The ECG-MATRIX is a pre-specified sub-study of the MATRIX programme which aims at analyzing the clinical value of ECG metrics in 4516 ACS patients (with and without ST-segment elevation in 2212 and 2304 cases, respectively) with matched pre and post-treatment ECGs. ConclusionsThis study represents a unique opportunity to further investigate the role of ECGs in the diagnosis and risk stratification of ACS patients with or without ST-segment deviation, as well as to assess whether the radial approach and bivalirudin may affect post-treatment ECG metrics and patterns in a large contemporary ACS population.
Abstract Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of ...AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio OR: 0.87; 95% confidence interval CI: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX MATRIX; NCT01433627 )
Nonirrigated magnetic ablation may result in potential char, ineffective lesions, and longer procedure times.
This study sought to report the safety and long-term efficacy of irrigated-tip magnetic ...ablation of atrial fibrillation (AF).
Catheter ablation was remotely performed using a new irrigated-tip magnetic catheter (ThermoCool NaviStar-RMT, Biosense Webster, Diamond Bar, CA) in 130 consecutive patients (mean age 59.7 ± 10.5 years) with symptomatic paroxysmal (81 patients) or persistent (49 patients) AF. The radiofrequency (RF) generator was set to fixed power of 30 W. The primary end point of the study was freedom from atrial tachycardia (AT)/AF off antiarrhythmic drugs.
The procedure was safely performed in all conventional ablation targets, but crossover to manual catheters was required in 12 patients to complete the mitral isthmus line. The total procedure time was 94.6 ± 15.3 minutes. Impedance values significantly decreased during RF applications (P < .001) and the maximum temperature on the catheter tip was 36.4°C ± 0.8°C. The follow-up duration was 15.3 ± 4.9 months. The primary end point was achieved in 66 of 81(81.4%) patients with paroxysmal AF and in 33 of 49 (67.3%) with persistent AF (P = .035, by log-rank test). Patients with paroxysmal AF had higher late AF recurrence (P =.044). Overall, postablation incessant left AT developed in 7 of 130 (5.4%) patients. Major complications were not observed. Left atrial diameter (P < .001) and heart failure (P = .032) predicted arrhythmia recurrence after remote irrigated-tip ablation.
Remote ablation with irrigated-tip magnetic catheters can be safely and effectively performed in patients with AF, but longer follow-up periods are required to evaluate late AF recurrences.
Contemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of ...patients with acute coronary syndrome (ACS) remains unclear.
The aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.
Patients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.
Among 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio HR: 2.37; 95% confidence interval CI: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 95% CI: 1.06 to 11.79; major: HR: 13.32 95% CI: 3.01 to 58.98).
Among patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627)
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The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of ...radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme.
MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70–100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50–70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627.
Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80–1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78–0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83–1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81–1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84–1·16; p=0·90).
In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management.
Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.
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