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Compared with metallic drug-eluting stents, bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention. Whether or not these devices are as safe and effective as drug-eluting stents within the first year after implantation is unknown. We did a patient-level, pooled meta-analysis of four randomised trials in which 3389 patients with stable coronary artery disease or a stabilised acute coronary syndrome were enrolled at 301 academic and medical centres in North America, Europe, and the Asia-Pacific region. These patients were randomly assigned to the everolimus-eluting Absorb BVS (n=2164) or the Xience cobalt-chromium everolimus-eluting stent (CoCr-EES; n=1225). The primary endpoints were the 1-year relative rates of the patient-oriented composite endpoint (all-cause mortality, all myocardial infarction, or all revascularisation) and the device-oriented composite endpoint of target lesion failure (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation). All analyses were by intention to treat. The four randomised trials included in our meta-analysis are all registered with ClinicalTrials.gov, numbers NCT01751906, NCT01844284, NCT01923740, and NCT01425281. The summary treatment effect for the 1-year relative rates of the patient-oriented composite endpoint did not differ significantly different between BVS and CoCr-EES (relative risk [RR] 1·09 [0·89–1·34], p=0·38). Similarly, the 1-year relative rates of the device-oriented composite endpoint did not differ between the groups (RR 1·22 [95% CI 0·91–1·64], p=0·17). Target vessel-related myocardial infarction was increased with BVS compared with CoCr-EES (RR 1·45 [95% CI 1·02–2·07], p=0·04), due in part to non-significant increases in peri-procedural myocardial infarction and device thrombosis with BVS (RR 2·09 [0·92–4·75], p=0·08). The relative rates of all-cause and cardiac mortality, all myocardial infarction, ischaemia-driven target lesion revascularisation, and all revascularisation did not differ between BVS and CoCr-EES. Results were similar after multivariable adjustment for baseline imbalances, and were consistent across most subgroups and in sensitivity analysis when two additional randomised trials with less than 1 year of follow-up were included. In this meta-analysis, BVS did not lead to different rates of composite patient-oriented and device-oriented adverse events at 1-year follow-up compared with CoCr-EES. Abbott Vascular.

The safety of drug-eluting stents has been called into question by recent reports of increased stent thrombosis, myocardial infarction, and death. Such studies have been inconclusive because of their insufficient size, the use of historical controls, a limited duration of follow-up, and a lack of access to original source data. We performed a pooled analysis of data from four double-blind trials in which 1748 patients were randomly assigned to receive either sirolimus-eluting stents or bare-metal stents and five double-blind trials in which 3513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents; we then analyzed the major clinical end points of the trials. The 4-year rates of stent thrombosis were 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P=0.20) and 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal-stent group (P=0.30). However, after 1 year, there were five episodes of stent thrombosis in patients with sirolimus-eluting stents versus none in patients with bare-metal stents (P=0.025) and nine episodes in patients with paclitaxel-eluting stents versus two in patients with bare-metal stents (P=0.028). The 4-year rates of target-lesion revascularization were markedly reduced in both the sirolimus-stent group and the paclitaxel-stent group, as compared with the bare-metal-stent groups. The rates of death or myocardial infarction did not differ significantly between the groups with drug-eluting stents and those with bare-metal stents. Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents. Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization. There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.

Glycated hemoglobin (HbA1c) is an approved and widely used laboratory investigation for diagnosis of diabetes that is not affected by acute changes in blood glucose. Our aim was to analyze the extent to which routine HbA1c measurements diagnose unknown diabetes mellitus (DM) in patients presenting with ST-segment elevation myocardial infarction (STEMI). We also compared outcomes in patients with newly diagnosed DM, previously established DM and those without DM. Consecutive patients undergoing PCI for STEMI from January 2005 to December 2012 were included and routinely performed admission HbA1c was used to identify patients with previously undiagnosed DM (HbA1c ≥6.5 and no history of DM or DM therapy) and pre-DM (HbA1c 5.7% to 6.4%). Overall 1,686 consecutive patients underwent primary percutaneous coronary intervention for STEMI during the study period and follow-up data were available for 1,566 patients (90%). A quarter of the patients (24%, n = 405) had history of DM, 7% (n = 118) had previously undiagnosed DM, and 38.7% (n = 652) had pre-DM. Mortality was comparable in patients with known DM and newly diagnosed DM both in-hospital (11.1% vs 11.9%, p = 0.87) and at 3-year follow-up (27.3% and 24%). Patients with DM, including those who were newly diagnosed, had higher mortality at 3 years (26.5%) compared to those with pre-DM (12.1%) or no dysglycemia (11.2%, p <0.01). In conclusion, a substantial number of patients with STEMI have previously undiagnosed DM (7%). These patients have similar in-hospital and long-term mortality as those with known DM, and outcomes are inferior to patients without dysglycemia.

Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7·2 [SD 3·4] vs 33·2 [6·0] cells/mm 2, n=4 per group, p<0·02) resulting in greater left-ventricular mass (1·24 [0·29] vs 1·57 [0·27] g) and better cardiac function (shortening fraction 9·2 [4·9] vs 17·2 [4·2]%, n=8 per group, p<0·05). These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is reestablished.

Randomized trials have demonstrated progressive improvements in clinical and angiographic measures of restenosis with technologic iterations from balloon angioplasty to bare-metal stents and subsequently to drug-eluting stents (DES). However, the permanent presence of a metal stent prevents coronary vasomotion, autoregulation, and adaptive coronary remodeling. The limitations imposed by a permanent metal implant may be overcome with a bioresorbable scaffold. ABSORB III is a large-scale, multicenter, randomized trial designed to support US premarket approval of the ABSORB BVS platform and is the first study with sufficient size to allow valid examination of the relative clinical outcomes between metallic DES and bioresorbable scaffold. ABSORB III (ClincalTrials.gov NCT01751906) will register approximately 2,262 patients and includes a lead-in phase (n = 50), the primary randomized analysis group (n = 2,000), an imaging cohort (n = 200), and a pharmacokinetic substudy (n = 12). In the primary analysis group, approximately 2,000 patients with up to 2 de novo native coronary artery lesions in separate epicardial vessels will be prospectively assigned in a 2:1 ratio to ABSORB BVS versus XIENCE everolimus-eluting stents (EES). The primary end point is target lesion failure (the composite of cardiac death, target vessel–related myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year, powered for noninferiority of ABSORB BVS compared to XIENCE EES. Clinical follow-up will continue for 5 years. Enrollment has been completed, and the principal results will be available in the fall of 2015. The large-scale ABSORB III randomized trial will evaluate the safety and effectiveness of ABSORB BVS compared to XIENCE EES in the treatment of patients with coronary artery disease.

In this trial, dabigatran plus a P2Y 12 inhibitor was compared with warfarin plus a P2Y 12 inhibitor and aspirin after PCI in patients with atrial fibrillation. The risk of bleeding was lower with dabigatran therapy; prevention of thromboembolic events was similar with the two strategies.

Bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention after their complete bioresorption. Randomised trials have shown non-inferiority between BVS and metallic drug-eluting stents at 1 year in composite safety and effectiveness outcomes, although some increases in rates of target vessel-related myocardial infarction and device thrombosis were identified. Outcomes of BVS following the first year after implantation are unknown. We sought to ascertain whether BVS are as safe and effective as drug-eluting stents within 2 years after implantation and between 1 and 2 years. We did a systematic review and meta-analysis of randomised trials in which patients were randomly assigned to everolimus-eluting Absorb BVS or metallic everolimus-eluting stents (EES) and followed up for at least 2 years. We searched MEDLINE, the Cochrane database, TCTMD, ClinicalTrials.gov, Clinical Trial Results, CardioSource, and abstracts and presentations from major cardiovascular meetings up to April 1, 2017, to identify relevant studies. The primary efficacy outcome measure was the device-oriented composite endpoint (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation) and the primary safety outcome measure was definite or probable device thrombosis. Individual patient data from the four ABSORB trials were used for landmark and subgroup analysis and multivariable modelling. We identified seven randomised trials in which 5583 patients were randomly assigned to Absorb BVS (n=3261) or metallic EES (n=2322) and followed up for 2 years. BVS had higher 2-year relative risks of the device-oriented composite endpoint than did EES (9·4% [304 of 3217] vs 7·4% [169 of 2299]; relative risk [RR] 1·29 [95% CI 1·08–1·56], p=0·0059). These differences were driven by increased rates of target vessel-related myocardial infarction (5·8% [187 of 3218] vs 3·2% [74 of 2299]; RR 1·68 [95% CI 1·29–2·19], p=0·0003) and ischaemia-driven target lesion revascularisation (5·3% [169 of 3217] vs 3·9% [90 of 2300]; 1·40 [1·09–1·80], p=0·0090) with BVS, with non-significant differences in cardiac mortality. The cumulative 2-year incidence of device thrombosis was higher with BVS than with EES (2·3% [73 of 3187] vs 0·7% [16 of 2281]; RR 3·35 [95% CI 1·96–5·72], p<0·0001). Landmark analysis between 1 and 2 years also showed higher rates of the device-oriented composite endpoint (3·3% [69 of 2100] vs 1·9% [23 of 1193]; RR 1·64 [95% CI 1·03–2·61], p=0·0376) and device thrombosis (0·5% [11 of 2085] vs none [0 of 1183], p<0·0001) in BVS-treated patients than in EES-treated patients. BVS was associated with increased rates of composite device-oriented adverse events and device thrombosis cumulatively at 2 years and between 1 and 2 years of follow-up compared with EES. Abbott Vascular.

In a randomized trial involving 2008 patients with coronary disease, an everolimus-eluting bioresorbable scaffold was noninferior to an everolimus-eluting cobalt–chromium stent with respect to target-lesion failure at 1 year. Contemporary drug-eluting coronary stents have been associated with better clinical outcomes than have either bare-metal stents or first-generation drug-eluting stents, but ongoing risks of stent thrombosis and restenosis limit their long-term safety and efficacy. 1 – 4 The development of late adverse events with permanent metallic stents may be related to persistent inflammation, loss of normal vessel curvature, impaired vasomotion, strut fracture, ongoing tissue growth within the stent frame, and neoatherosclerosis. 5 , 6 Furthermore, 20 to 30% of patients have recurrent angina during the first year after implantation of a drug-eluting stent. 7 – 9 In this context, stents that are fully bioresorbable have been . . .

Background Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD). A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. Results Microarray analysis of RNA samples from a 195 patient Duke CATHGEN registry case:control cohort yielded 2,438 genes with significant CAD association (p < 0.05), and identified the clinical/demographic factors with the largest effects on gene expression as age, sex, and diabetic status. RT-PCR analysis of 88 CAD classifier genes confirmed that diabetic status was the largest clinical factor affecting CAD associated gene expression changes. A second microarray cohort analysis limited to non-diabetics from the multi-center PREDICT study (198 patients; 99 case: control pairs matched for age and sex) evaluated gene expression, clinical, and cell population predictors of CAD and yielded 5,935 CAD genes (p < 0.05) with an intersection of 655 genes with the CATHGEN results. Biological pathway (gene ontology and literature) and statistical analyses (hierarchical clustering and logistic regression) were used in combination to select 113 genes for RT-PCR analysis including CAD classifiers, cell-type specific markers, and normalization genes. RT-PCR analysis of these 113 genes in a PREDICT cohort of 640 non-diabetic subject samples was used for algorithm development. Gene expression correlations identified clusters of CAD classifier genes which were reduced to meta-genes using LASSO. The final classifier for assessment of obstructive CAD was derived by Ridge Regression and contained sex-specific age functions and 6 meta-gene terms, comprising 23 genes. This algorithm showed a cross-validated estimated AUC = 0.77 (95% CI 0.73-0.81) in ROC analysis. Conclusions We have developed a whole blood classifier based on gene expression, age and sex for the assessment of obstructive CAD in non-diabetic patients from a combination of microarray and RT-PCR data derived from studies of patients clinically indicated for invasive angiography. Clinical trial registration information PREDICT, P ersonalized R isk E valuation and D iagnosis i n the C oronary T ree, http://www.clinicaltrials.gov , NCT00500617

Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided pnon-inferiority=0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided pnon-inferiority=0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 459 (36·8%) patients assigned to BVS and 494 (39·1%) patients assigned to EES (difference –2·3%, 95% CI –6·1% to 1·5%; one-sided pnon-inferiority=0·0001; two-sided psuperiority=0·2404). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586). Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. Abbott Vascular.