Adrian P. Banning

Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions

Background—Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations. Methods and Results—We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P <0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P <0.0001) and from 20.2% to 4.7% in the MR cohort (P =0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P =0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients. Conclusions—Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions.

Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study).

BACKGROUND Acute coronary, cerebrovascular, and peripheral vascular events have common underlying arterial pathology, risk factors, and preventive treatments, but they are rarely studied concurrently. In the Oxford Vascular Study, we determined the comparative epidemiology of different acute vascular syndromes, their current burdens, and the potential effect of the ageing population on future rates. METHODS We prospectively assessed all individuals presenting with an acute vascular event of any type in any arterial territory irrespective of age in a population of 91 106 in Oxfordshire, UK, in 2002-05. FINDINGS 2024 acute vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618 stroke, 300 transient ischaemic attacks [TIA]); 856 (42%) coronary vascular (159 ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction, 218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43 aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and 62 unclassifiable deaths. Relative incidence of cerebrovascular events compared with coronary events was 1.19 (95% CI 1.06-1.33) overall; 1.40 (1.23-1.59) for non-fatal events; and 1.21 (1.04-1.41) if TIA and unstable angina were further excluded. Event and incidence rates rose steeply with age in all arterial territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%) peripheral vascular events in 12 886 (14%) individuals aged 65 years or older; and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75 years or older. Although case-fatality rates increased with age, 736 (47%) of 1561 non-fatal events occurred at age 75 years or older. INTERPRETATION The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial

BACKGROUND The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING The Health Foundation (UK) and European Society of Vascular Surgery.

Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: insights from cardiovascular magnetic resonance imaging

Background—Although troponin elevation after percutaneous coronary intervention (PCI) is common, uncertainties remain about the mechanisms of its release and its relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of the heart has been shown to reliably quantify areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac troponin release, we studied the incidence and extent of new irreversible injury in patients undergoing PCI and correlated it to postprocedural changes in cardiac troponin I. Methods and Results—Fifty patients undergoing PCI were studied with preprocedural and postprocedural (24 hours) delayed-enhancement MRI for assessment of new irreversible myocardial injury. Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI. Of these 50 patients, 24 underwent a further third MRI scan at a median of 8 months after the procedure. Mean patient age was 64±12 years. After the procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement, with a mean mass of 6.0±5.8 g, or 5.0±4.8% of total left ventricular mass. All of these patients had raised troponin I levels (range 1.0 to 9.4 &mgr;g/L). Thirty-four patients (68%) had no elevated troponin I and no evidence of new myocardial necrosis on MRI. There was a strong correlation between the rise in troponin I measurements at 24 hours and mean mass of new myocardial hyperenhancement, both early (r=0.84; P<0.001) and late (r=0.71; P<0.001) after PCI, although there was a trend for a reduction in the size of PCI-induced myocardial injury in the late follow-up scan (P=0.07). Conclusions—In the setting of PCI, patients demonstrating postprocedural elevation in troponin I have evidence of new irreversible myocardial injury on delayed-enhancement MRI. The magnitude of this injury correlates directly with the extent of troponin elevation.

Clinical Efficacy of Polymer-Based Paclitaxel-Eluting Stents in the Treatment of Complex, Long Coronary Artery Lesions From a Multicenter, Randomized Trial. Support for the Use of Drug-Eluting Stents in Contemporary Clinical Practice

Background— Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking. Methods and Results— TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001). Conclusions— The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.

Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease: Comparison of Outcomes With Cardiac Surgery and Paclitaxel-Eluting Stents

OBJECTIVES This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease. BACKGROUND Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial. METHODS The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG. RESULTS The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001). CONCLUSIONS Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although further study is needed, these exploratory results may extend the evidence for PES use in selected patients with less complex left main and/or 3-vessel lesions. (SYNergy Between PCI With TAXus and Cardiac Surgery [SYNTAX]; NCT00114972).

Treatment of complex coronary artery disease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial

OBJECTIVES This prespecified subgroup analysis examined the effect of diabetes on left main coronary disease (LM) and/or three-vessel disease (3VD) in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the SYNTAX trial. METHODS Patients (n = 1800) with LM and/or 3VD were randomized to receive either PCI with TAXUS Express paclitaxel-eluting stents or CABG. Five-year outcomes in subgroups with (n = 452) or without (n = 1348) diabetes were examined: major adverse cardiac or cerebrovascular events (MACCE), the composite safety end-point of all-cause death/stroke/myocardial infarction (MI) and individual MACCE components death, stroke, MI and repeat revascularization. Event rates were estimated with Kaplan-Meier analyses. RESULTS In diabetic patients, 5-year rates were significantly higher for PCI vs CABG for MACCE (PCI: 46.5% vs CABG: 29.0%; P < 0.001) and repeat revascularization (PCI: 35.3% vs CABG: 14.6%; P < 0.001). There was no difference in the composite of all-cause death/stroke/MI (PCI: 23.9% vs CABG: 19.1%; P = 0.26) or individual components all-cause death (PCI: 19.5% vs CABG: 12.9%; P = 0.065), stroke (PCI: 3.0% vs CABG: 4.7%; P = 0.34) or MI (PCI: 9.0% vs CABG: 5.4%; P = 0.20). In non-diabetic patients, rates with PCI were also higher for MACCE (PCI: 34.1% vs CABG: 26.3%; P = 0.002) and repeat revascularization (PCI: 22.8% vs CABG: 13.4%; P < 0.001), but not for the composite end-point of all-cause death/stroke/MI (PCI: 19.8% vs CABG: 15.9%; P = 0.069). There were no differences in all-cause death (PCI: 12.0% vs CABG: 10.9%; P = 0.48) or stroke (PCI: 2.2% vs CABG: 3.5%; P = 0.15), but rates of MI (PCI: 9.9% vs CABG: 3.4%; P < 0.001) were significantly increased in the PCI arm in non-diabetic patients. CONCLUSIONS In both diabetic and non-diabetic patients, PCI resulted in higher rates of MACCE and repeat revascularization at 5 years. Although PCI is a potential treatment option in patients with less-complex lesions, CABG should be the revascularization option of choice for patients with more-complex anatomic disease, especially with concurrent diabetes.

Incomplete Stent Apposition After Implantation of Paclitaxel-Eluting Stents or Bare Metal Stents Insights From the Randomized TAXUS II Trial

Background—The clinical impact of late incomplete stent apposition (ISA) for drug-eluting stents is unknown. We sought to prospectively investigate the incidence and extent of ISA after the procedure and at 6-month follow-up of paclitaxel-eluting stents in comparison with bare metal stents (BMS) and survey the clinical significance of ISA over a period of 12 months. Methods and Results—TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This intravascular ultrasound (IVUS) substudy included patients who underwent serial IVUS examination after the procedure and at 6 months (BMS, 240 patients; SR, 113; MR, 116). The qualitative and quantitative analyses of ISA were performed by an independent, blinded core laboratory. More than half of the instances of ISA observed after the procedure resolved at 6 months in all groups. No difference in the incidence of late-acquired ISA was observed among the 3 groups (BMS, 5.4%; SR, 8.0%; MR, 9.5%; P=0.306), with a similar ISA volume (BMS, 11.4 mm3; SR, 21.7 mm3; MR, 8.5 mm3; P=0.18). Late-acquired ISA was the result of an increase of vessel area without change in plaque behind the stent. Predictive factors of late-acquired ISA were lesion length, unstable angina, and absence of diabetes. No stent thrombosis occurred in the patients diagnosed with ISA over a period of 12 months. Conclusions—The incidence and extent of late-acquired ISA are comparable in paclitaxel-eluting stents and BMS. ISA is a pure IVUS finding without clinical repercussions.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

BACKGROUND Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING Biosensors, Aarhus University Hospital, and participating sites.