Rationale and study protocol for the BRITISH randomized trial (Using cardiovascular magnetic resonance identified scar as the benchmark risk indication tool for implantable cardioverter defibrillators in patients with nonischemic cardiomyopathy and severe systolic heart failure).

BACKGROUND: For patients with nonischemic cardiomyopathy (NICM), current guidelines recommend implantable cardioverter defibrillators (ICD) when left ventricular ejection fraction (LVEF) is ≤35%, but the DANISH trial failed to confirm that ICDs reduced all-cause mortality for such patients. Circumstantial evidence suggests that scar on CMR is predictive of sudden and arrhythmic death in this population. The presence of myocardial scar identified by cardiac magnetic resonance imaging (CMR) in patients with NICM and an LVEF ≤35% might identify patients at higher risk of sudden arrhythmic death, for whom an ICD is more likely to reduce all-cause mortality. METHODS/DESIGN: The BRITISH trial is a prospective, multicenter, randomized controlled trial aiming to enrol 1,252 patients with NICM and an LVEF ≤35%. Patients with a nonischemic scar on CMR will be randomized to either: (1) ICD, with or without cardiac resynchronization (CRT-D), or (2) implantable loop recorder (ILR) or cardiac resynchronization (CRT-P). Patients who are screened for the trial but are found not to be eligible, predominantly due to an absence of scar or those who decline to be randomized will be enrolled in an observational registry. The primary endpoint is all-cause mortality, which we plan to assess at 3 years after the last participant is randomized. Secondary endpoints include clinical outcomes, appropriate and inappropriate device therapies, symptom severity and well-being, device-related complications, and analysis of the primary endpoint by subgroups with other risk markers. CONCLUSION: The BRITISH trial will assess whether the use of CMR-defined scar to direct ICD implantation in patients with NICM and an LVEF ≤35% is associated with a reduction in mortality.

Vascular complications associated with intraaortic balloon pump supported percutaneous coronary intervention (PCI) and clinical outcomes from the British Cardiovascular Intervention Society National PCI Database.

INTRODUCTION: The impact of a vascular complication (VC) in the setting of intraaortic balloon pump (IABP) supported PCI on clinical outcomes is unclear. METHODS: Using data from the BCIS National PCI Database, multivariate logistic regression was used to identify independent predictors of a VC. Propensity scoring was used to quantify the association between a VC and outcomes. RESULTS: Between 2007 and 2014, 9,970 PCIs in England and Wales were supported by IABP (1.6% of total PCI), with 224 femoral VCs (2.3%). Annualized rates of a VC reduced as the use of radial access for PCI increased. The independent predictors of a VC included a procedural complication (odds ratio [OR] 2.9, p < .001), female sex (OR 2.3, p < .001), PCI for stable angina (OR 3.47, p = .028), and use of a glycoprotein inhibitor (OR 1.46 [1.1:2.5], p = .04), with a lower likelihood of a VC when radial access was used for PCI (OR 0.48, p = .008). A VC was associated with a higher likelihood of transfusion (OR 5.7 [3.5:9.2], p < .0001), acute kidney injury (OR 2.6 [1.2:6.1], p = .027), and periprocedural MI (OR 3.2 [1.5:6.7], p = .002) but not with adjusted mortality at discharge (OR 1.2 [0.8:1.7], p = .394) or 12-months (OR 1.1 [0.76:1.56], p = .639). In sensitivity analyses, there was a trend towards higher mortality in patients experiencing a VC who underwent PCI for stable angina (OR 4.1 [1.0:16.4], p value for interaction .069). Discussion and Conclusions Although in-hospital morbidity was observed to be adversely affected by occurrence of a VC during IABP-supported PCI, in-hospital and 1-year survival were similar between groups.

Temporal Changes in Co-Morbidity Burden in Patients Having Percutaneous Coronary Intervention and Impact on Prognosis.

This study aims to evaluate the impact of co-morbidity burden on outcomes in patients who undergo percutaneous coronary intervention (PCI). We used the Nationwide Inpatient Sample to identify all PCI procedures undertaken in the United States from 2004 to 2014. We then determined co-morbidity burden for each patient record based on the Charlson Co-morbidity Score. Multivariable logistic regression models were used to examine the association between co-morbidity burden and in-hospital mortality other in-hospital complications. A total of 6,601,526 PCI procedures were included in the analysis. Overall co-morbidity burden increased over time, with severe co-morbidity burden (defined as a CCI score ≥3) increasing from 5.3% in 2004 to 14.2% in 2014 (p <0.0001). After adjustment for confounding factors increasing co-morbidity burden was independently associated with increased odds of in-hospital mortality, complications, length of hospital stay, and total cost of hospitalization post PCI. A CCI score of 1 was independently associated with an increase in the odds of in hospital mortality (odds ratio [OR] 1.19 [95% confidence interval [CI] 1.15 to 1.25]), a score of 2 associated with an almost 1.5-fold increase (OR 1.41 [95% CI 1.34 to 1.48]) and a score of ≥3 a 2-fold increase (OR 1.96 [95% CI 1.86 to 2.07]) compared with no co-morbid burden (CCI score of 0). In conclusion, our results show that co-morbid burden is independently associated with increased risk of in-hospital mortality, in-hospital complications, length of stay, and healthcare costs.

Does the Routine Availability of CT-Derived FFR Influence Management of Patients With Stable Chest Pain Compared to CT Angiography Alone?: The FFRCT RIPCORD Study.

OBJECTIVES: This study sought to determine the effect of adding computed tomography-derived fractional flow reserve (FFRCT) data to computed tomography angiographic (CTA) data alone for assessment of lesion severity and patient management in 200 patients with chest pain. BACKGROUND: Invasive and noninvasive tests used in the assessment of patients with angina all have disadvantages. The ideal screening test for patients presenting for the first time with chest pain would describe both coronary anatomy and the presence of ischemia and would be readily accessible, low cost, and noninvasive. METHODS: Two hundred patients with stable chest pain underwent CTA for clinical reasons, and FFRCT was calculated. Three experienced interventional cardiologists assessed the CTA result for each patient and by consensus developed a management plan (optimal medical therapy, percutaneous coronary intervention, coronary artery bypass graft surgery, or more information required). FFRCT data for each vessel were then revealed, and the interventional cardiologists made a second plan by consensus, using the same 4 options. The primary endpoint for the study was the difference between the 2 strategies. RESULTS: Overall, after disclosure of FFRCT data there was a change in the allocated management category on the basis of CTA alone in 72 cases (36%). This difference is explained by a discordance between the CTA- and FFRCT-derived assessments of lesion severity. For example, FFRCT was >0.80 in 13 of 44 vessels (29.5%) graded as having a stenosis >90%. In contrast, FFRCT was ≤0.80 in 17 of 366 vessels (4.6%) graded as having stenosis ≤50%. CONCLUSIONS: This study demonstrates proof of concept that the availability of FFRCT results has a substantial effect on the labeling of significant coronary artery disease and therefore on the management of patients compared to CTA alone. Further studies are needed to determine whether FFRCT has potential as a noninvasive diagnostic and management screening tool for patients with stable chest pain.

Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study.

AIMS: Randomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety. Here, we report the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation coronary stenting trials with similar methodology: the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study: old, new, and evolving strategies (BBC ONE). METHODS AND RESULTS: Both multicentre randomized trials compared simple (provisional T-stenting) vs. complex (culotte, crush, and T-stenting) techniques, using drug-eluting stents. We analysed all-cause death at 5 years. Data were collected from phone follow-up, hospital records, and national mortality tracking. Follow-up was complete for 890 out of 913 patients (97%). Both Simple and Complex groups were similar in terms of patient and lesion characteristics. Five-year mortality was lower among patients who underwent a simple strategy rather than a complex strategy [17 patients (3.8%) vs. 31 patients (7.0%); P = 0.04]. CONCLUSION: For coronary bifurcation lesions, a provisional single-stent approach appears to be associated with lower long-term mortality than a systematic dual stenting technique.

Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression.

BACKGROUND AND AIMS: n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15-18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time. METHODS: In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study. RESULTS: 92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005-0.020 mm) compared to 0.015 mm (IQR 0.007-0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized ß-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized ß-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized ß-coefficient -0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized ß-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized ß-coefficient -0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18. CONCLUSION: Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.

Predictors of inhospital mortality following out-of-hospital cardiac arrest: Insights from a single-centre consecutive case series.

PURPOSE OF THE STUDY: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis despite bystander resuscitation and rapid transfer to hospital. Optimal management of patients after arrival to hospital continues to be contentious, especially the timing of emergency coronary angiography±revascularisation. Robust predictors of inhospital outcome would be of clinical value for initial decision-making. STUDY DESIGN: A retrospective analysis of consecutive patients who presented to a university hospital following OHCA over a 70-month period (2008-2013). Patients were identified from the emergency department electronic patient registration and coding system. For those patients who underwent emergency percutaneous coronary intervention, details were crosschecked with national databases. RESULTS: We identified 350 consecutive patients who were brought to our hospital following OHCA. Return of spontaneous circulation (ROSC) for >20 min was achieved either before arrival or inhospital in 196 individuals. From the 350 subjects, 114 (32.6%) survived to hospital discharge. When sustained ROSC was achieved, either before or inhospital, survival to discharge was 58.2% (114 of 196). Non-shockable rhythm, absence of bystander cardiopulmonary resuscitation, 'downtime' >15 min and initial pH ≤7.11 were predictors of inhospital death. 12% patients who underwent angiography in the presence of ST elevation had no acute coronary occlusion. 21% patients with acute coronary occlusion at angiography did not have ST elevation. CONCLUSIONS: In our cohort of patients with OHCA, those who achieve ROSC had a survival-to-discharge rate of 58.2%. We identified four predictors of inhospital death, which are readily available at the time of patient presentation. Reliance on ST elevation to decide about coronary angiography and revascularisation may be flawed. More data are required.

Potential eligibility of congenital heart disease patients for subcutaneous implantable cardioverter-defibrillator based on surface electrocardiogram mapping.

AIMS: The eligibility of complex congenital heart disease (C-CHD) patients for subcutaneous implantable cardioverter-defibrillator (S-ICD) has yet to be determined. The aim of this study was to determine in C-CHD patients: (i) the S-ICD eligibility, (ii) the most effective sensing vector, (iii) the impact of posture change on screening eligibility, and (iv) the impact of using two vs. six postures for screening. Adults with structurally normal hearts were used as controls. METHODS AND RESULTS: The Boston Scientific ECG screening tool was used to determine eligibility for S-ICD in two and six different postures in 30 patients with C-CHD and 10 controls. Statistical significance was determined using Fisher's exact test. In total, 1440 bipolar vectors were collected. The mean age was 36.3 years, 57% subjects were men. Over all 86.7% of C-CHD patients and 100% controls (P > 0.05) met S-ICD eligibility. In controls, the primary vector (PV) was the most effective, and the alternate vector (AV) was least effective. In C-CHD patients, the AV was comparable to the PV. Posture change did not significantly affect S-ICD eligibility in C-CHD patients and controls (P > 0.05). Screening with six postures vs. two did not significantly affect S-ICD eligibility of C-CHD patients (83% vs. 87%, P > 0.05) or controls (90% vs. 100% P = >0.05). CONCLUSION: No significant differences were observed between S-ICD eligibility in C-CHD patients and controls. The AV and PV are most suitable in C-CHD patients. No significant impact of postural change was observed for S-ICD eligibility between the two groups. No significant difference was observed in S-ICD eligibility when screening using two or six postures in both groups.

Detection of regional myocardial ischaemia by a novel 80-electrode body surface Delta map in patients presenting to the emergency department with cardiac-sounding chest pain.

BACKGROUND: Presentation with acute chest pain is common, but the conventional 12-lead ECG has limitations in the detection of regional myocardial ischaemia. The previously described method of the body surface mapping system (BSM) Delta map, derived from an 80-electrode BSM, as well as a novel parameter total ischaemic burden (IB), may offer improved diagnostic sensitivity and specificity in patients with myocardial ischaemia. METHODS: The feasibility of using the novel BSM Delta map technique, and IB, for transient regional myocardial ischaemia was assessed in comparison with 12-lead ECG in 49 patients presenting to the emergency department (ED) with cardiac-sounding chest pain. RESULTS: The sensitivity and specificity of 12-lead ECG for the diagnosis of acute coronary syndrome (ACS) was 67 and 55%, respectively, positive likelihood ratio (+LR) 1.52 [95% confidence interval (CI) 0.86, 2.70] and negative likelihood ratio (-LR) 0.58 [95% CI 0.30, 1.12]. The sensitivity and specificity of the BSM Delta map for the diagnosis of ACS was 71 and 78%, +LR 3.19 [95% CI 1.31, 7.80], -LR 0.37 [95% CI 0.20, 0.68]. There was a significantly positive correlation between peak troponin-I concentration and IB (r=0.437; P<0.002). CONCLUSION: This pilot study confirms the feasibility of using the Delta map for the diagnosis of ACS in patients presenting to the ED with cardiac-sounding chest pain and suggests that it has promising diagnostic accuracy and has superior sensitivity and specificity to the 12-lead ECG. The novel parameter of IB shows a significant correlation with troponin-I and is a promising tool for describing the extent of ischaemia. The use of the BSM Delta map in the ED setting could improve the diagnosis of clinically important ischaemic heart disease and furthermore presents the result in an intuitive manner, requiring little specialist experience. Further larger scale study is now warranted.

Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients with stable coronary artery disease: Results of the SWAP-2 Study (Switching Anti Platelet-2).

OBJECTIVES: The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel. BACKGROUND: Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues. METHODS: After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization. RESULTS: Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups. CONCLUSIONS: Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.

What is the optimum adjunctive reperfusion strategy for primary percutaneous coronary intervention?

Acute ST-segment elevation myocardial infarction (STEMI) is a dynamic, thrombus-driven event. As understanding of its pathophysiology has improved, the central role of platelets in initiation and orchestration of this process has become clear. Key components of STEMI include formation of occlusive thrombus, mediation and ultimately amplification of the local vascular inflammatory response resulting in increased vasoreactivity, oedema formation, and microvascular obstruction. Activation, degranulation, and aggregation of platelets are the platforms from which these components develop. Therefore, prompt, potent, and predictable antithrombotic therapy is needed to optimise clinical outcomes after primary percutaneous coronary intervention. We review present pharmacological and mechanical adjunctive therapies for reperfusion and ask what is the optimum combination when primary percutaneous coronary intervention is used as the mode of revascularisation in patients with STEMI.

Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design.

AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. METHODS AND RESULTS: CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. CONCLUSIONS: The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

Nonalcoholic fatty liver disease and vascular risk.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, which is strongly associated with obesity and diabetes. The risk of cardiovascular disease is increased in NAFLD and represents the main cause of death in these patients. However, given the shared features between NAFLD, the metabolic syndrome and traditional cardiovascular risk factors, uncertainty exists as to whether NAFLD is an independent risk factor for increased cardiovascular disease. RECENT FINDINGS: Multiple epidemiological and case-control studies now demonstrate that NAFLD is associated with increased vascular risk, independently of conventional cardiometabolic risk factors. Evidence also suggests a graded association between NAFLD severity and increased vascular risk. However, given the heterogeneous disease spectrum of NAFLD, these findings have limitations with respect to accuracy of diagnosis and staging of NAFLD in most studies. SUMMARY: Although accumulating evidence points to NAFLD emerging as a novel cardiovascular risk factor, more research is needed to find suitable noninvasive biomarkers of NAFLD severity to allow better risk-stratification based on cardiovascular outcomes. Furthermore, with no established pharmacological treatment option for NAFLD currently available, any potential treatment must show efficacy not only in slowing liver disease progression, but also in ameliorating adverse cardiovascular outcomes.

Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.

Drug eluting stents for the treatment of bare metal in-stent restenosis: long-term outcomes in real world practice.

AIMS: Drug eluting stents (DES) have had a great impact in reducing in-stent restenosis (ISR) in de novo lesions. However, long-term data regarding effectiveness and safety of these stents in treating bare metal stent (BMS) ISR are limited. We report long-term clinical outcomes in a cohort of patients with BMS-ISR treated with DES between April 2002 and December 2003 at our institution. METHODS AND RESULTS: Sixty-nine consecutive patients with significant BMS-ISR were treated with DES implantation. Sirolimus DES were used in 43 patients and paclitaxel DES in 26. All patients were followed up to determine the incidence of major adverse cardiac event (MACE) rates (all-cause death, myocardial infarction, or target vessel revascularisation [TVR]), angina class and the need for clinically driven angiography. The mean age of the cohort was 58.6 ± 10.8 years; 68% were male, 33% were diabetic, 50% had hypertension, 78% were on statin therapy and 59% were current (19%) or previous (41%) smokers. The clinical presentation of ISR was with chronic stable angina in 54 patients, 12 had a non-ST elevation acute coronary syndrome and three presented with ST-elevation myocardial infarction. Multivessel stenting was performed in 21 patients and bifurcation stenting in seven patients. Over a mean follow period of 4.9 years, the first event MACE rate was 20% (17 events in 14 patients - eight deaths of which three were cardiac, two non-fatal myocardial infarctions and seven TVR). Excluding non-cardiac death, the adjusted MACE rate was 14.5% (12 events in 10 patients). At long-term follow-up, mean Canadian angina class decreased from 2.3 ± 0.7 pre-procedure to 1.2 ± 0.4, 65% of patients were angina free and 80% were free of MACE. No differences in long-term outcomes were observed between patients receiving paclitaxel and sirolimus DES. CONCLUSIONS: The use of DES for the treatment of BMS-ISR is safe and effective over a mean follow-up period of nearly five years. To our knowledge, this represents the longest follow-up data of real world patients treated in a single interventional centre.

Simple or complex stenting for bifurcation coronary lesions: a patient-level pooled-analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study.

BACKGROUND: Controversy persists regarding the correct strategy for bifurcation lesions. Therefore, we combined the patient-level data from 2 large trials with similar methodology: the NORDIC Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study (BBC ONE). METHODS AND RESULTS: Both randomized trials compared simple (provisional T-stenting) versus complex techniques, using drug-eluting stents. In the simple group (n=457), 129 patients had final kissing balloon dilatation in addition to main vessel stenting, and 16 had T-stenting. In the complex group (n=456), 272 underwent crush, 118 culotte, and 59 T-stenting techniques. A composite end point at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of the simple versus 17.3% of the complex group (hazard ratio 1.84 [95% confidence interval 1.28 to 2.66], P=0.001). Procedure duration, contrast, and x-ray dose favored the simple approach. Subgroup analysis revealed similar composite end point results for true bifurcations (n=657, simple 9.2% versus complex 17.3%; hazard ratio 1.90 [95% confidence interval 1.22 to 2.94], P=0.004), wide-angled bifurcations >60 to 70° (n=217, simple 9.6% versus complex 15.7%; hazard ratio 1.67 [ 95% confidence interval 0.78 to 3.62], P=0.186), large (≥2.75 mm) diameter side branches (n=281, simple 10.4% versus complex 20.7%; hazard ratio 2.42 [ 95% confidence interval 1.22 to 4.80], P=0.011), longer length (>5 mm) ostial side branch lesions (n=464, simple 12.1% versus complex 19.1%; hazard ratio 1.71 [95% confidence interval 1.05 to 2.77], P=0.029), or equivalent sized vessels (side branch <0.25 mm smaller than main vessel) (n=108, simple 12.0% versus complex 15.5%; hazard ratio 1.35 [95% confidence interval 0.48 to 3.70], P=0.57). CONCLUSIONS: For bifurcation lesions, a provisional single-stent approach is superior to systematic dual stenting techniques in terms of safety and efficacy. A complex approach does not appear to be beneficial in more anatomically complicated lesions.

Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists?

Aspirin is now widely accepted as the first-line antithrombotic platelet therapy for at-risk individuals. During the last decade or so it has also become established that co-administering antagonists of the ADP receptor P2Y(12) with aspirin further reduces the risk of acute thrombotic events. By the nature of its evolution, this therapeutic approach assumes that P2Y(12) receptor antagonists will be added to aspirin, and this therefore dominates the design of clinical trials. This strategy has resulted in the generation of a large body of clinical evidence showing the benefit of aspirin plus P2Y(12) receptor antagonists, largely from studies with clopidogrel and more recently from those with prasugrel and ticagrelor, but with obvious limitations in terms of residual ischaemic event rates and bleeding complications. It is our hypothesis, however, that when administered in the presence of potent P2Y(12) receptor antagonists, aspirin could actually increase total cardiovascular risk, although this has never been tested in large outcome studies. Clearly, this potentially negative interaction could be of relevance to millions of patients.

A novel paclitaxel-eluting stent with an ultrathin abluminal biodegradable polymer 9-month outcomes with the JACTAX HD stent.

OBJECTIVES: The JACTAX HD trial ("JACTAX" Trial Drug Eluting Stent Trial) evaluated the safety and clinical performance of a novel JACTAX HD (Boston Scientific Corporation, Natick, Massachusetts) paclitaxel-eluting stent (PES) in de novo coronary lesions. BACKGROUND: The JACTAX HD (Boston Scientific) stent consists of a pre-crimped bare-metal Liberté (Boston Scientific) stent coated on its abluminal aspect with an ultrathin (<1 microm) 1/1 mixture of biodegradable polylactide polymer and paclitaxel applied as discrete microdots (nominal totals of 9.2 microg each of polymer and paclitaxel per 16-mm stent). METHODS: In this prospective, single-arm, multicenter, first-human-use study (n = 103), the primary end point of 9-month major adverse cardiac events (MACE) (cardiac death, myocardial infarction, ischemia-related target vessel revascularization) was compared with an objective performance criterion (OPC) of 17% (11% MACE based on TAXUS ATLAS [TAXUS Liberté-SR Stent for the Treatment of de Novo Coronary Artery Lesions] trial results plus a pre-specified noninferiority margin of 6%). RESULTS: The composite primary end point occurred in 7.8% of JACTAX HD patients with an upper 1-sided 95% confidence limit of 13.6%, thus meeting the pre-specified criteria for noninferiority. There was no death, Q-wave myocardial infarction, or stent thrombosis through 9 months. In-stent late loss was 0.33 +/- 0.45 mm, with an in-stent binary restenosis of 5.2% and net volume obstruction by intravascular ultrasound of 11.4 +/- 11.2%. CONCLUSIONS: The JACTAX HD stent with an abluminal biodegradable polymer showed 9-month MACE, in-stent late loss, restenosis, and net volume obstruction comparable to that observed with the TAXUS Liberté (Boston Scientific) stent coated with a conformal durable polymer. Further studies are underway to better evaluate the potential of this new PES design, which might allow for more rapid endothelialization and improved vessel healing. ("JACTAX" Trial Drug Eluting Stent Trial; NCT00754728).