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Aims: We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced-induced thrombus deposition was determined using 125I-fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface-induced thrombus formation, with a significant difference compared to Vision (125I-fibrinogen median value deposition [IQ range]: 50 ng [25-98] versus 560 ng [320-1520], respectively, p < 0.05), but not to other DES. In the second set of experiments Fluoropolymer-coated BMS not eluting drug was associated with a significant 3-fold reduction in 125I-fibrinogen deposition (245 ng [80-300]) compared to Vision (625 ng [320-760], p < 0.05), but a 7-fold increase compared to Xience (35 ng [20-60], p < 0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface-induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.

Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. Methods Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Results Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality (Pinteraction=.03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG (Pinteraction

Background: The role of thrombus aspiration plus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction remains controversial. Methods: We performed a meta-analysis of 25 randomised controlled trials in which 21,740 ST-segment elevation myocardial infarction patients were randomly assigned to thrombus aspiration plus primary percutaneous coronary intervention or primary percutaneous coronary intervention. Study endpoints were: death, myocardial infarction, stent thrombosis and stroke. Results: On pooled analysis, the risk of death (4.3% vs. 4.8%, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.79–1.03; P=0.123), myocardial infarction (2.4% vs. 2.5%, OR 0.95, 95% CI 0.80–1.13; P=0.57) and stent thrombosis (1.3% vs. 1.6%, OR 0.80, 95% CI 0.63–1.01; P=0.066) was similar between thrombus aspiration plus primary percutaneous coronary intervention and primary percutaneous coronary intervention. The risk of stroke was higher in the thrombus aspiration plus primary percutaneous coronary intervention than the primary percutaneous coronary intervention group (0.84% vs. 0.59%, OR 1.401, 95% CI 1.004–1.954; P=0.047). However, on sensitivity analysis after removing the TOTAL trial, thrombus aspiration plus primary percutaneous coronary intervention was not associated with an increased risk of stroke (OR 1.01, 95% CI 0.58–1.78). The weak association between thrombus aspiration and stroke was also confirmed by the fact that the lower bound of the 95% CI was slightly below unity after removing either the study by Kaltoft or the ITTI trial. There was no interaction between the main study results and follow-up, evidence of coronary thrombus, or study sample size. Conclusions: In patients with ST-segment elevation myocardial infarction, thrombus aspiration plus primary percutaneous coronary intervention does not reduce the risk of death, myocardial infarction or stent thrombosis. Thrombus aspiration plus primary percutaneous coronary intervention is associated with an increased risk of stroke; however, this latter finding appears weak.

Objectives This study sought to investigate the impact of nonemergent, uncomplicated target lesion revascularization (TLR) on the risk of long-term mortality after percutaneous coronary intervention (PCI). Background Restenosis requiring TLR after PCI is generally considered a benign event. Methods The study pooled patient-level data from 21 randomized trials. Subjects dying the same day as or the day after the TLR procedure as well as those with myocardial infarction (MI) the day before, the same day as or the day after TLR were excluded. The primary endpoint of the study was all-cause mortality. Results The dataset included 32,524 patients who were stratified according to whether repeat TLR was performed during follow-up. During a median follow-up of 37 months, 2,330 (7.2%) patients underwent a nonemergent, uncomplicated TLR procedure. After adjusting for potential confounders, TLR was an independent predictor of mortality (hazard ratio: 1.23, 95% confidence interval: 1.04 to 1.45; p = 0.02). Patients undergoing nonemergent, uncomplicated TLR had significantly higher rates of non–procedure-related MI compared with those without TVR. Among patients undergoing elective TLR, MI occurring after TLR was an independent predictor of mortality (hazard ratio: 3.82; 95% confidence interval: 2.44 to 5.99; p Conclusions Nonemergent, uncomplicated TLR after PCI is an independent predictor of long-term mortality, an association in part explained by higher rates of MI occurring after TLR. Efforts aimed at reducing TLR risk may translate into prognostic benefits including reduced rates of MI and survival.

Background: Accuracy of high sensitive troponin (hs-cTn) to detect coronary artery disease (CAD) in patients with renal insufficiency is not established. The aim of this study was to evaluate the prognostic role of hs-cTn T and I in patients with chronic kidney disease (CKD). Methods: All consecutive patients with chest pain, renal insufficiency (eGFR < 60 mL/min/1.73 m2) and high sensitive troponin level were included. The predictive value of baseline and interval troponin (hs-cTnT and hs-cTnI) for the presence of CAD was assessed. Results: One hundred and thirteen patients with troponin I and 534 with troponin T were included, with 95 (84%) and 463 (87%) diagnosis of CAD respectively. There were no differences in clinical, procedural and outcomes between the two assays. For both, baseline hs-cTn values did not differ be­tween patients with/without CAD showing low area under the curve (AUC). For interval levels, hs-cTnI was significantly higher for patients with CAD (0.2 ± 0.8 vs. 8.9 ± 4.6 ng/mL; p = 0.04) and AUC was more accurate for troponin I than hs-cTnT (AUC 0.85 vs. 0.69). Peak level was greater for hs-cTnI in patients with CAD or thrombus (0.4 ± 0.6 vs. 15 ± 20 ng/mL; p = 0.02; AUC 0.87: 0.79–0.93); no differences were found for troponin T assays (0.8 ± 1.5 vs. 2.2 ± 3.6 ng/mL; p = 1.7), with lower AUC (0.73: 0.69–0.77). Peak troponin levels (both T and I) independently predicted all cause death at 30 days. Conclusions: Patients with CKD presenting with altered troponin are at high risk of coronary disease. Peak level of both troponin assays predicts events at 30 days, with troponin I being more accurate than troponin T. (Cardiol J 2017; 24, 2: 139–150)

Large clinical trials and meta-analyses have shown that thrombus aspiration (TA) in the setting of ST-T segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) does not improve clinical outcome, whilst it may be associated with an increased risk of stroke. Accordingly, in the most recent European Society of Cardiology guidelines the role of routine TA during PPCI has been downgraded to a class III recommendation with level A of evidence. On the other hand, it has been suggested that in case of high thrombus burden a selective use of TA may still play a role. STEMI due to cardioembolism (CE) definitely represents one of these situations. In the present case of an 81-year-old woman presenting with STEMI due to a cardioembolic obstruction of left main coronary artery, we show that TA succeeded, whereas classical angioplasty failed, in promoting a prompt coronary flow restoration in a life-threatening condition. Further, it allowed us not to upgrade the procedure with stent implantation that would have required a triple antithrombotic therapy, significantly increasing the bleeding risk. Visual examination of thrombi retrieved suggested the diagnosis of CE. Finally, we clearly show which is the mechanism linking TA with the risk of stroke.

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score. We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA. The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test

Objective To determine, in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the prognostic weight of cardiac arrest (CA) according to the type of rhythm (shockable vs. non-shockable). Methods We prospectively enrolled 3278 consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used to establish the relation to 1-year cardiac mortality of both type of CA. In patients suffering from CA we identified predictors of both poor neurological outcome (cerebral performance categories 3–5) and cardiac mortality at 1 year. Results The incidence of CA was 7.26% (n = 238). Of these, 196 (5.98%) had an initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm (adjusted-HR = 1.61; 95%CI 1.08–2.43, p = 0.02) and non-shockable rhythm (adjusted-HR = 3.83; 95%CI 2.36–6.22, p < 0.001) were independently associated with 1-year cardiac mortality. Among patients with CA those with shockable rhythm had a lower risk of poor neurological outcome at 1 year follow up (adjusted OR = 0.22: 95%CI; 0.08–0.55, p = 0.001). Independent predictors of 1-y cardiac mortality were: non shockable rhythm (adjusted HR = 2.6; 95%CI; 1.48–4.5, p = 0.001), crew-witnessed CA, diabetes mellitus, left ventricle ejection fraction and creatinine on admission. There was a significant interaction between type of rhythm and crew-witnessed CA (p = 0.026). Conclusions In patients with STEMI undergoing PPCI patients with both shockable and non shockable CA are at increased risk of 1-year cardiac mortality. Among patients with CA those with non shockable rhythm have an higher risk of both poor neurological outcome and cardiac mortality at 1 year.

Background Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety and efficacy of these devices are unknown. Many recent studies have now reported extended follow-up data. Objectives This study sought to investigate the long-term safety and efficacy of durable polymer-based DES, bioabsorbable polymer-based biolimus-eluting stents (BES), and BMS by means of network meta-analysis. Methods Randomized controlled trials comparing DES to each other or to BMS were searched through MEDLINE, EMBASE, and Cochrane databases and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Results Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target-vessel revascularization were reduced with all DES compared with BMS, with cobalt-chromium EES, platinum chromium-EES, SES, and BES also having lower target-vessel revascularization rates than PES. Conclusions After a median follow-up of 3.8 years, all DES demonstrated superior efficacy compared with BMS. Among DES, second-generation devices have substantially improved long-term safety and efficacy outcomes compared with first-generation devices.

Background Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE). Objectives This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis. Methods Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis). Results Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT. Conclusions Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment -P2Y(12) platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index >= 50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p=0.009). This finding was confirmed also among statin-treated patients with high Syntax score (>= 15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p=0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

Background Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear. Objectives The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs. Methods RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded. Results Individual patient data were obtained for 6 RCTs, and aggregate data were available for 12 RCTs. Patients with bleeding had significantly higher rates of mortality compared with those without, and in a time-adjusted multivariate analysis, bleeding was an independent predictor of mortality occurring within 1 year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53 to 10.60; p< 0.0001). Shorter DAPT was associated with lower rates of all-cause death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval: 0.73 to 1.00; p= 0.05), which was driven by lower rates of bleeding-related deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95% confidence interval: 0.43 to 0.99; p= 0.04). Mortality unrelated to bleeding was comparable between the 2groups. Similar results were apparent in the modified intention-to-treat population. Conclusions Bleeding was strongly associated with the occurrence of mortality within 1 year after the bleeding event. Shorter compared with longer DAPT was associated with lower risk for bleeding-related death, a finding that mayunderlie the lower all-cause mortality with shorter DAPT in the RCTs of different DAPT durations after DES.

Objectives This study sought to investigate the relative safety and efficacy of bioabsorbable polymer (BP)-based biolimus-eluting stents (BES) versus durable-polymer (DP)-drug-eluting stents (DES) and bare-metal stents (BMS) by means of a network meta-analysis. Background Studies have suggested that BP-BES might reduce the risk of stent thrombosis (ST) and late adverse outcomes compared with first-generation DES. However, the relative safety and efficacy of BP-BES versus newer-generation DES coated with more biocompatible DP have not been investigated in depth. Methods Randomized controlled trials comparing BP-BES versus currently U.S.-approved DES or BMS were searched through MEDLINE, EMBASE, and Cochrane databases. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Results Data from 89 trials including 85,490 patients were analyzed. At 1-year follow-up, BP-BES were associated with lower rates of cardiac death/myocardial infarction (MI), MI, and target vessel revascularization (TVR) than BMS and lower rates of TVR than fast-release zotarolimus-eluting stents. The BP-BES had similar rates of cardiac death/MI, MI, and TVR compared with other second-generation DP-DES but higher rates of 1-year ST than cobalt-chromium everolimus-eluting stents (CoCr-EES). The BP-BES were associated with improved late outcomes compared with BMS and paclitaxel-eluting stents, considering the latest follow-up data available, with nonsignificantly different outcomes compared with other DP-DES although higher rates of definite ST compared with CoCr-EES. Conclusions In this large-scale network meta-analysis, BP-BES were associated with superior clinical outcomes compared with BMS and first-generation DES and similar rates of cardiac death/MI, MI, and TVR compared with second-generation DP-DES but higher rates of definite ST than CoCr-EES.

First-generation drug-eluting stents (DES), which impart the controlled release of sirolimus or paclitaxel from durable polymers to the vessel wall, have been consistently shown to reduce the risk of restenosis and target vessel revascularization compared with bare metal stents (BMS). However, stent thrombosis (ST) emerged as a major safety concern with first-generation DES early after their adoption in clinical practice, requiring prolonged dual antiplatelet therapy. Pathological studies have shown that first-generation DES are associated with delayed arterial healing and polymer hypersensitivity reactions resulting in chronic inflammation, predisposing to late and very late ST. Second-generation DES have been developed to overcome these issues with improved stent designs and construction and the use of biocompatible and bioabsorbable polymers. Meta-analyses have shown that the thin-strut, fluoropolymer-coated cobalt-chromium everolimus-eluting stent (CoCr-EES) may be associated with lower rates of definite ST than other DES and, unexpectedly, even lower than BMS. The thin-strut structure of the stent platform, the thromboresistant properties of the fluoropolymer, and the reduced polymer and drug load may contribute to the low rate of ST with CoCr-EES. The notion of DES being safer than BMS represents a paradigm shift in the evolution of percutaneous coronary intervention. The relative safety and efficacy of fluoropolymer-coated CoCr-EES, DES with bioabsorbable polymers, and fully bioresorbable scaffolds are the subject of numerous ongoing large-scale trials.

Aims: In patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI, high (H) platelet reactivity (PR) significantly affects one-year outcome. The aim of this report was to analyse the relationships between HPR, the SYNTAX score (SS) and one-year major adverse cardiac events (MACE: cardiac death, myocardial infarction, stent thrombosis) according to diabetes mellitus (DM) status in patients included in the GEne Polymorphism, Platelet REactivity, and the Syntax Score (GEPRESS) study.Methods and results: PR was measured using the vasodilator-stimulated phosphoprotein (VASP) assay at three time points (before PCI, at hospital discharge and at one month after PCI), with HPR defined as >50% PR index in 1,042 patients treated with aspirin and clopidogrel for one year after PCI. Patients with DM and an SS >= 15 had the highest MACE rate between one month and one year, further increased by the presence of HPR (16.4%). On the other hand, among all patients with an SS = 15 and HPR characterised a cohort with the highest MACE rate from one month to one year. In such high-risk patients, careful clinical monitoring and implementation of secondary prevention measures, including the use of potent P2Y(12) inhibitors, are strongly advised.

Objectives This study sought to develop a new score specific for patients with non–ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) (the ACUITY-PCI [Acute Catheterization and Urgent Intervention Triage Strategy–Percutaneous Coronary Intervention] risk score). Background The TIMI (Thrombolysis In Myocardial Infarction) and GRACE (Global Registry for Acute Coronary Events) risk scores are recommended for risk stratification of patients with NSTEACS. However, these scores were not optimized for patients undergoing an early invasive strategy with PCI. Methods The ACUITY-PCI risk score was created from data for 1,692 patients enrolled in the formal angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial by integrating clinical, angiographic, laboratory, and electrocardiographic variables selected by multivariable analysis. The score was subsequently validated in a different population of 846 patients and compared with the GRACE and TIMI risk scores, and the SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) and Clinical SYNTAX scores. Results Six variables (2 clinical, 1 laboratory/electrocardiographic, and 3 angiographic) were included in the ACUITY-PCI score: insulin-treated diabetes; renal insufficiency; baseline cardiac biomarker elevation or ST-segment deviation; bifurcation lesion; small vessel/diffuse coronary artery disease; and the extent of coronary artery disease. Event rates increased significantly across tertiles of ACUITY-PCI score. Compared with the other scores, the ACUITY-PCI score had the best discrimination (C-statistic), calibration (Hosmer-Lemeshow statistic), and index of separation. Moreover, the net reclassification improvement varied from 9% to 38% and the integrated discrimination index from 1.9% to 2.7%. Conclusions The ACUITY-PCI risk score is a new tool integrating clinical, angiographic, and laboratory/electrocardiographic variables specifically developed for patients with NSTEACS undergoing PCI. This score displayed better prognostic accuracy in terms of discrimination and calibration than other currently available scores for risk stratification of patients with NSTEACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158 )

We thank the correspondents for their interest in our meta-analysis in which we reported a significant association between extended dual antiplatelet therapy (DAPT) duration and bleeding-related deaths in patients treated with drug-eluting stents [(1)][1]. Regarding the issues raised by Drs. Bittl

Introduction: Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention. Methods: Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients. Results: Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p

Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety and efficacy of these devices are unknown. Many recent studies have now reported extended follow-up data.This study sought to investigate the long-term safety and efficacy of durable polymer-based DES, bioabsorbable polymer-based biolimus-eluting stents (BES), and BMS by means of network meta-analysis.Randomized controlled trials comparing DES to each other or to BMS were searched through MEDLINE, EMBASE, and Cochrane databases and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted.Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target-vessel revascularization were reduced with all DES compared with BMS, with cobalt-chromium EES, platinum chromium-EES, SES, and BES also having lower target-vessel revascularization rates than PES.After a median follow-up of 3.8 years, all DES demonstrated superior efficacy compared with BMS. Among DES, second-generation devices have substantially improved long-term safety and efficacy outcomes compared with first-generation devices.

none 19 si Abstract BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. METHODS: We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. FINDINGS: We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. INTERPRETATION: Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. Palmerini, T; Benedetto, U; Bacchi-Reggiani, L; Riva, Dd; Biondi-Zoccai, G; Feres, F; Abizaid, A; Hong, Mk; Kim, Bk; Jang, Y; Kim, Hs; Park, Kw; Genereux, P; Bhatt, Dl; Orlandi, C; De Servi, S; Petrou, M; Rapezzi, C; Stone, Gw Palmerini, T; Benedetto, U; Bacchi-Reggiani, L; Riva, Dd; Biondi-Zoccai, G; Feres, F; Abizaid, A; Hong, Mk; Kim, Bk; Jang, Y; Kim, Hs; Park, Kw; Genereux, P; Bhatt, Dl; Orlandi, C; De Servi, S; Petrou, M; Rapezzi, C; Stone, Gw

none 24 si Aim We sought to determine whether theoptimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary studyoutcome was the 1- year composite risk of myocardial infarction (MI)or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MIor ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P=0.71; Pinteraction=0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MIor ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify theoptimal duration of DAPT after DES in individual patients basedon their relative ischaemic and bleeding risks. Palmerini, Tullio; Della Riva, Diego; Benedetto, Umberto; Bacchi Reggiani, Letizia; Feres, Fausto; Abizaid, Alexandre; Gilard, Martine; Morice, Marie-Claude; Valgimigli, Marco; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Colombo, Antonio; Chieffo, Alaide; Sangiorgi, Diego; Biondi-Zoccai, Giuseppe; Généreux, Philippe; Angelini, Gianni D.; Pufulete, Maria; White, Jonathon; Bhatt, Deepak L.; Stone, Gregg W Palmerini, Tullio; Della Riva, Diego; Benedetto, Umberto; Bacchi Reggiani, Letizia; Feres, Fausto; Abizaid, Alexandre; Gilard, Martine; Morice, Marie-Claude; Valgimigli, Marco; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Colombo, Antonio; Chieffo, Alaide; Sangiorgi, Diego; Biondi-Zoccai, Giuseppe; Généreux, Philippe; Angelini, Gianni D.; Pufulete, Maria; White, Jonathon; Bhatt, Deepak L.; Stone, Gregg W

Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE).This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis.Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis).Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT.Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.

Aims Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) perform similarly in terms of lowering mortality and myocardial infarction rates in patients with stable angina, except in subjects with high-risk lesions. PCI is burdened from higher rates of revascularization, but offers a reduction in stroke. To date, the impact of clinical variables on the risk-benefit assessment has not been established. Methods and results Using event rates as a dependent variable, meta-regression was performed to test whether an interaction existed between baseline clinical features (age, gender, diabetes mellitus, previous myocardial infarction and ejection fraction) and choice of revascularization, focusing on death, myocardial infarction, repeat revascularization and stroke. 20 randomized clinical trials (RCT) including 12,844 patients with stable angina were included. Compared to CABG, PCI significantly reduced the risk of stroke, both at 30 days (odds ratio [OR] 0.36 [95% confidence interval: 0.20–0.62]) and at follow up (median = 12 months, OR = 0.57 [0.41–0.80]). This reduction in stroke was significantly higher in females (B = − 0.12, p = 0.03). For repeat revascularization, PCI performed worse than CABG, both in the overall population and in patients with multivessel disease (OR = 4.71 [3.17–7.01]) and (OR = 7.18 [4.32–11.93]). Women (B = 3.4, p = 0.01) and those with diabetes mellitus (B = 1.8, p = 0.002) were at increased risk of subsequent revascularization after PCI. Conclusion PCI significantly reduces the risk of stroke compared to CABG particularly in female patients: however the risk of revascularization is increased with PCI, especially in women and in those with diabetes.

Background— Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. Methods and Results— Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P =0.0004; cardiac death: 2.0% versus 6.9%; respectively; P Conclusions— In patients with ST-segment–elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00433966.

Although it has been shown that elevated white blood cell count (WBCc) on presentation is associated with an increased risk of cardiac mortality in patients with ST-segment elevation myocardial infarction (STEMI), the responsible mechanisms are unknown. We therefore sought to investigate whether elevated WBCc is associated with increased infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention in the Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction trial. INFUSE AMI randomized patients with STEMI and proximal or mid-left anterior descending coronary artery occlusion to bolus intracoronary abciximab versus no abciximab and to manual aspiration versus no aspiration. WBCc at hospital admission was available in 407 of 452 randomized patients. Patients were stratified according to tertiles of WBCc. At 30 days, a significant stepwise increase in infarct size (percentage of total left ventricular mass) was apparent across tertiles of increasing WBCc (median [interquartile range] for tertiles I vs II vs III = 11.2% [3.8% to 19.6%] vs 17.5% [0.5% to 22.9%] vs 19.1% [13.7 to 26.0], respectively, p0.0001). Absolute infarct mass in grams and abnormal wall motion score were also significantly increased across tertiles of WBC. By multivariate linear regression analysis, WBCc was an independent predictor of infarct size along with intracoronary abciximab randomization, age, time from symptom onset to first device, proximal left anterior descending location, and baseline TIMI flow of 0/1. In conclusion, in patients with anterior wall STEMI, an elevated admission WBCc is a powerful independent predictor of infarct size measured with cardiac magnetic resonance imaging 30 days after primary percutaneous coronary intervention.

The authors investigated the relative safety and efficacy of different drug-eluting stents (DES) and bare metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) using a network meta-analysis.The relative safety of DES and BMS in patients with STEMI continues to be debated, and whether advances have been made in this regard with second-generation DES is unknown.Randomized controlled trials comparing currently U.S. approved DES or DES with BMS in patients with STEMI were searched using MEDLINE, EMBASE, and Cochrane databases. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted.Twenty-two trials including 12,453 randomized patients were analyzed. At 1-year follow-up, cobalt-chromium everolimus eluting stents (CoCr-EES) were associated with significantly lower rates of cardiac death or myocardial infarction (MI) and stent thrombosis (ST) than BMS. Differences in ST were apparent as early as 30 days and were maintained for 2 years. CoCr-EES were also associated with significantly lower rates of 1-year ST than paclitaxel-eluting stents (PES). Sirolimus-eluting stents (SES) were also associated with significantly lower rates of 1-year cardiac death/myocardial infarction than BMS. CoCr-EES, PES, and SES, but not zotarolimus-eluting stents, had significantly lower rates of 1-year target vessel revascularization (TVR) than BMS, with SES also showing lower rates of TVR than PES.In patients with STEMI, steady improvements in outcomes have been realized with the evolution from BMS to first-generation and now second-generation DES, with the most favorable safety and efficacy profile thus far demonstrated with CoCr-EES.

Although inflammation is involved in the pathogenesis of acute coronary syndromes, the extent of inflammation is not routinely assessed, and its prognostic implications in patients with non-ST-segment elevation acute coronary syndrome have not been investigated in depth. We analyzed the prognostic implications of an elevated white blood cell count (WBCc) in patients with moderate and high-risk non-ST-segment elevation acute coronary syndrome undergoing an early invasive strategy in the large-scale Acute Catheterization and Urgent Intervention Triage StrategY trial. The WBCc at admission was available for 13,678 of 13,819 patients (98.9%). The patients in the upper tertile of the WBCc had an increased risk of 30-day major bleeding, 1-year mortality, and definite/probable stent thrombosis compared to those in the mid or lower tertiles. On multivariate analysis, the WBCc was an independent predictor of 30-day major bleeding and 1-year cardiac, noncardiac, and all-cause mortality. The association between the WBCc and cardiac mortality was present in multiple prespecified subgroups, with no significant interaction between the WBCc and age, gender, diabetes, smoking, renal dysfunction, elevated baseline biomarkers, antithrombotic therapy, revascularization, and Thrombolysis In Myocardial Infarction risk score. The WBCc remained an independent predictor of mortality after adjusting for bleeding, C-reactive protein level, and angiographic variables, including left ventricular ejection fraction, Thrombolysis In Myocardial Infarction flow, and number of diseased vessels. The WBCc significantly improved the prognostic accuracy of the Thrombolysis In Myocardial Infarction risk score, with a net reclassification improvement of 11% (p0.0001). In conclusion, in patients with moderate- and high-risk non-ST-segment elevation acute coronary syndrome, an elevated admission WBCc was an independent predictor of 30-day major bleeding, and 1-year cardiac, noncardiac, and all-cause mortality.

Summary Background The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. Methods For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Findings 49 trials including 50 844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13–0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11–0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08–0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16–0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24–0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10–0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03–0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17–0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19–0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. Interpretation In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. Funding The Cardiovascular Research Foundation.

Background Although some trials have reported that on-pump coronary artery bypass graft (CABG) surgery may be associated with higher rates of stroke than percutaneous coronary intervention (PCI), whether stroke is more common after off-pump CABG compared with PCI is unknown. We therefore sought to determine whether off-pump CABG is associated with an increased risk of stroke compared with PCI by means of network meta-analysis. Methods Randomized controlled trials (RCTs) comparing CABG vs PCI were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Results Eighty-three RCTs with 22,729 patients randomized to on-pump CABG (n = 10,957), off-pump CABG (n = 7,119), or PCI (n = 4,653) were analyzed. Thirty-day rates of stroke were significantly lower in patients treated with PCI compared with either off-pump CABG (odds ratio [OR]; 0.39, 95% CI, 0.19-0.83) or on-pump CABG (OR, 0.26; 95% CI, 0.12-0.47). Compared with on-pump CABG, off-pump CABG was associated with significantly lower 30-day risk of stroke (OR, 0.67; 95% CI, 0.41-0.95). However, in sensitivity analyses restricted to high-quality studies, studies with more than either 100 or 1,000 patients, or studies with protocol definition or adjudication of stroke by a clinical events committee, the precision of the point estimate for the 30-day risk of stroke between off-pump vs on-pump CABG was markedly reduced. Conclusions Percutaneous coronary intervention is associated with lower 30-day rates of stroke than both off-pump and on-pump CABG. Further studies are required to determine whether the risk of stroke is reduced with off-pump CABG compared with on-pump CABG.

ObjectivesThe aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI).BackgroundPlatelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this category of patients remains challenging.MethodsThe GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year.ResultsBetween 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS