Randomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study).

BACKGROUND: First-generation drug-coated balloons (DCBs) have significantly reduced the rate of restenosis compared with balloon angioplasty alone; however, high rates of bailout stenting and dissections persist. The Chocolate Touch DCB is a nitinol constrained balloon designed to reduce acute vessel trauma and inhibit neointima formation and restenosis. METHODS: Patients with claudication or ischemic rest pain (Rutherford class 2-4) and superficial femoral or popliteal disease (≥70% stenosis) were randomized 1:1 to Chocolate Touch or Lutonix DCB at 34 sites in the United States, Europe, and New Zealand. The primary efficacy end point was DCB success, defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of clinically driven bailout stenting). The primary safety end point was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. Both primary end points were tested for noninferiority, and if met, sequential superiority testing for efficacy followed by safety was prespecified. An independent clinical events committee, and angiographic and duplex ultrasound core laboratories blinded to treatment allocation reviewed all end points. RESULTS: A total of 313 patients were randomized to Chocolate Touch (n=152) versus Lutonix DCB (n=161). Follow-up at 1 year was available in 94% of patients. The mean age was 69.4±9.5 years, the average lesion length was 78.1±46.9 mm, and 46.2% had moderate-to-severe calcification. The primary efficacy rates of DCB success at 12 months was 78.8% (108/137) with Chocolate Touch and 67.7% (88/130) with Lutonix DCB (difference, 11.1% [95% CI, 0.6-21.7]), meeting noninferiority (Pnoninferiority<0.0001) and sequential superiority (Psuperiority=0.04). The primary safety event rate was 88.9% (128/144) with Chocolate Touch and 84.6% (126/149) with Lutonix DCB (Pnoninferiority<0.001; Psuperiority=0.27). CONCLUSIONS: In this prospective, multicenter, randomized trial, the second-generation Chocolate Touch DCB met both noninferiority end points for efficacy and safety and was more effective than Lutonix DCB at 12 months for the treatment of femoropopliteal disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924857.

Chocolate Touch Versus Lutonix Drug-Coated Balloon for Femoropopliteal Lesions in Diabetes: The Chocolate Touch Study.

BACKGROUND: The randomized Chocolate Touch Study demonstrated that in patients undergoing treatment of femoropopliteal artery lesions, the Chocolate Touch drug-coated balloon (DCB) was safe and had superior efficacy at 12 months compared with the Lutonix DCB. We report the prespecified diabetes subanalysis comparing outcomes among patients with and without diabetes mellitus (DM). METHODS: Patients with claudication or ischemic rest pain (Rutherford class 2-4) were randomized to Chocolate Touch or Lutonix DCB. The primary efficacy endpoint was DCB success defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of bailout stenting). The primary safety endpoint was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. RESULTS: A total of 313 patients (38% DM [n=119]) were randomized to either Chocolate Touch (n=66/152) or Lutonix DCB (n=53/161). Among patients with DM, DCB success was 77.2% and 60.5% (p=0.08), and in non-DM patients, DCB success was 80% and 71.3% (p=0.2114) for the Chocolate Touch and Lutonix DCB, respectively. The primary safety endpoint was similar for both cohorts regardless of DM status (interaction test, p=0.96). CONCLUSIONS: This randomized trial demonstrated similar safety and efficacy for the treatment of femoropopliteal disease with the Chocolate Touch DCB compared with using the Lutonix DCB regardless of DM status at 12 months. CLINICAL IMPACT: This substudy of the Chocolate Touch Study demonstrated similar safety and efficacy for treatment of femoropopliteal disease of the Chocolate Touch DCB compared with the Lutonix DCB regardless of diabetes (DM) status at 12 months. Endovascular therapy has become the therapy of choice for the treatment of most symptomatic femoropopliteal lesions regardless of DM status. These results give clinicians another option when treating femoropopliteal disease in this high-risk patient population.

Novel Supreme Drug-Eluting Stents With Early Synchronized Antiproliferative Drug Delivery to Inhibit Smooth Muscle Cell Proliferation After Drug-Eluting Stents Implantation in Coronary Artery Disease: Results of the PIONEER III Randomized Clinical Trial.

BACKGROUND: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known. METHODS: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure-a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776). RESULTS: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, -1.87 to 2.5]; Pnoninferiority=0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46-1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non-clinically driven target lesion revascularization at 12 months were higher with Supreme DES. CONCLUSIONS: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

A prospective randomized evaluation of the TriGuard™ HDH embolic DEFLECTion device during transcatheter aortic valve implantation: results from the DEFLECT III trial.

AIMS: To evaluate the safety, efficacy, and performance of the TriGuard™ HDH Embolic Deflection Device (TriGuard) compared with no cerebral protection in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: From February 2014 to March 2015, 85 subjects undergoing TAVI at 13 centres in Europe and Israel were randomized to TriGuard protection vs. no protection. Subjects underwent neurologic and cognitive evaluation at baseline, pre-discharge and 30 days; cerebral diffusion-weighted magnetic resonance imaging was performed at 4 ± 2 days post-procedure and at 30 days. Technical success, which included complete 3-vessel cerebral coverage, was achieved in 88.9% (40/45) of cases. The primary in-hospital procedural safety endpoint (death, stroke, life-threatening or disabling bleeding, stage 2 or 3 acute kidney injury, or major vascular complications) occurred in 21.7% of TriGuard and 30.8% of control subjects (P = 0.34). In the Per Treatment population (subjects with complete three-vessel cerebral coverage), TriGuard use was associated with greater freedom from new ischaemic brain lesions (26.9 vs. 11.5%), fewer new neurologic deficits detected by the National Institutes of Health Stroke Scale (3.1 vs. 15.4%), improved Montreal Cognitive Assessment (MoCA) scores, better performance on a delayed memory task (P = 0.028) at discharge, and a >2-fold increase in recovery of normal cognitive function (MoCA score >26) at 30 days. CONCLUSION: TriGuard cerebral protection during TAVI is safe and complete cerebral vessel coverage was achieved in 89% of subjects. In this exploratory study, subjects undergoing protected TAVI had more freedom from ischaemic brain lesions, fewer neurologic deficits, and improved cognitive function in some domains at discharge and 30 days compared with controls.

Local delivery of paclitaxel in the treatment of peripheral arterial disease.

BACKGROUND: Despite advancements from balloon angioplasty to drug-eluting stents, primary patency rates after endovascular revascularization of peripheral artery disease have remained inferior compared to surgery. Endovascular revascularization has been limited by restenosis and mechanical stent failure. Thus, there is increased research into other nonstent-based local drug delivery modalities, which can provide an active drug to inhibit restenosis focally and avoid the risk of systemic adverse effects. METHODS: This review will summarize the unique properties of paclitaxel and studies on paclitaxel local delivery for the treatment of peripheral artery disease. A MEDLINE search for relevant peer-reviewed scientific literature published in English was conducted. Search terms included but were not limited to paclitaxel pharmacodynamics, paclitaxel local drug delivery, and drug eluting balloons, with a focus on the use of paclitaxel in the context of coronary and peripheral vascular disease. RESULTS: The primary search produced 182 results of which 51 papers were relevant. Of the 51 relevant papers, 27 were original research papers and 24 were either review papers, commentary or opinion papers. CONCLUSIONS: Paclitaxel has several chemical properties, which make it ideal for local drug delivery including its hydrophobicity, ability to concentrate into the arterial intima layer and prolonged effect on cells even after brief exposure periods. Local delivery of paclitaxel via injection catheters, balloon catheters and coated balloons has shown encouraging results in terms of efficacy and safety in small-scale animal and clinical studies. Additional preclinical and clinical studies are needed to determine the long-term efficacy and safety of these treatments in humans.

Clinical Significance of Diffusion-Weighted Brain MRI Lesions After TAVR: Results of a Patient-Level Pooled Analysis.

BACKGROUND: Acute brain infarction detected by diffusion-weighted magnetic resonance imaging (DW-MRI) is common after transcatheter aortic valve replacement (TAVR), but its clinical relevance is uncertain. OBJECTIVES: The authors investigated the relationship between DW-MRI total lesion number (TLN), individual lesion volume (ILV), and total lesion volume (TLV) and clinical stroke outcomes after TAVR. METHODS: Patient-level data were pooled from 4 prospective TAVR embolic protection studies, with consistent predischarge DW-MRI acquisition and core laboratory analysis. C-statistic was used to determine the best DW-MRI measure associated with clinical stroke. RESULTS: A total of 495 of 603 patients undergoing TAVR completed the predischarge DW-MRI. At 30 days, the rate of clinical ischemic stroke was 6.9%. Acute ischemic brain injury was seen in 85% of patients with 5.5 ± 7.3 discrete lesions per patient, mean ILV of 78.2 ± 257.1 mm3, and mean TLV of 555 ± 1,039 mm3. The C-statistic was 0.84 for TLV, 0.81 for number of lesions, and 0.82 for maximum ILV in predicting ischemic stroke. On the basis of the TLV cutpoint as defined by receiver operating characteristic (ROC), patients with a TLV >500 mm3 (vs TLV ≤500 mm3) had more ischemic stroke (18.2% vs 2.3%; P < 0.0001), more disabling strokes (8.8% vs 0.9%; P < 0.0001), and less complete stroke recovery (44% vs 62.5%; P = 0.001) at 30 days. CONCLUSIONS: Our study confirms that the number, size, and total volume of acute brain infarction defined by DW-MRI are each associated with clinical ischemic strokes, disabling strokes, and worse stroke recovery in patients undergoing TAVR and may have value as surrogate outcomes in stroke prevention trials. (A Prospective, Randomized Evaluation of the TriGuard™ HDH Embolic Deflection Device During TAVI [DEFLECT III]; NCT02070731) (A Study to Evaluate the Neuro-embolic Consequences of TAVR [NeuroTAVR]; NCT02073864) (The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation [REFLECT I]; NCT02536196) (The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation [REFLECT II]; NCT02536196).

Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry.

Background: Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. Methods: The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. Conclusions: DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.

Cerebral Embolic Risk in Coronary and Structural Heart Interventions: Clinical Evidence.

Surgical and endovascular procedures for coronary and structural heart interventions carry a meaningful risk of acute stroke with greatly increased likelihood of disability and long-term neurocognitive sequelae. In the last decade, transcatheter aortic valve replacement procedures have focused our attention on a spectrum of procedure-related neurologic injuries that have led to various efforts to prevent ischemic injury with the use of embolic protection devices. As the number of patients undergoing surgical and transcatheter cardiac procedures in the United States continues to increase, the risk of iatrogenic brain injury is concerning, particularly in patient populations already at increased risk of thromboembolism and cognitive decline. In this study, we reviewed the current estimates of the incidence of iatrogenic cerebral embolization and ischemic infarction after surgical and percutaneous transcatheter interventions for coronary artery disease, stenotic aortic and mitral valves, atrial fibrillation, left atrial appendage and patent foramen ovale closure. Our findings show that every year in the United States, nearly 2 million patients undergo coronary and structural heart interventions, with approximately 8000 at risk of experiencing a symptomatic stroke and 330,225 (95% CI, 249,948-430,377) at the risk of ischemic brain injury after the procedure. Given the increased use of surgical and endovascular cardiac procedures in clinical practice, the risk of iatrogenic cerebral embolism is significant and demands careful consideration through neurologic and cognitive assessments and appropriate risk mitigation.

The Supreme Biodegradable Polymer DES in Acute and Chronic Coronary Syndromes: A PIONEER III Substudy.

Background: The PIONEER III trial demonstrated noninferiority of 12-month target lesion failure (TLF) with the Supreme DES (Sinomed), a thin-strut cobalt-chromium, biodegradable polymer, sirolimus-eluting stent, compared with a durable polymer, everolimus-eluting (XIENCE/PROMUS) stent (DP-EES). The relative safety and effectiveness of the Supreme DES in patients with acute coronary syndromes (ACS) and those with chronic coronary syndromes (CCS) is not known. Methods: PIONEER III was a prospective, multicenter, international, 2:1 randomized trial stratified by clinical presentation. The primary end point was TLF at 12 months (a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization). Results: A total of 1628 patients were enrolled, including 41% of patients with ACS (unstable angina and non-ST-elevation myocardial infarction) randomized to Supreme DES (n = 441) versus DP-EES (n = 232) and 59% of patients with CCS randomized to Supreme DES (n = 645) versus DP-EES (n = 310). Patients with ACS were younger, fewer presented with less diabetes, hypertension, and previous revascularization, but more were current smokers. The primary end point of TLF (6.4% vs 4.4%; P = .1), major adverse cardiac events (8.5% vs 6.5%; P = .16), and stent thrombosis (0.4% vs 0.9%; P = .25) at 12 months were similar in the ACS and CCS groups. There was no difference in TLF at 12 months between Supreme DES and DP-EES among patients with ACS (6.6% vs 6.0%; P = .89) and those with CCS (4.5% vs 4.3%; P = .83); interaction P = .51 for TLF by clinical presentation. Conclusions: Compared with the DP-EES, the Supreme DES seemed safe and effective with a similar TLF at 12 months in both patients with ACS and those with CCS.

Geographic Variations on the Safety and Efficacy of the Supreme Biodegradable Polymer DES: Results From PIONEER III.

Background: The PIONEER III trial showed the 12-month safety and efficacy of the Supreme drug-eluting stent (DES) vs the durable polymer everolimus-eluting stent. We sought to assess whether the characteristics and clinical outcomes of the Supreme DES in PIONEER III were consistent among patients by enrollment location. Methods: This subgroup analysis of the PIONEER III trial compared the characteristics and outcomes of patients recruited from North America, Europe, and Japan and the relative differences in patient outcomes according to the site recruitment volume. Results: From October 2017 to July 2019, 1629 patients were recruited in North America (816, 50.1%), Europe (650, 39.9%), and Japan (163, 10%). Procedural success was achieved in 1556 of 1611 procedures (96.6%), with no difference by the geographic location. Target lesion failure at 12 months for combined groups was observed in 84 of 1629 patients (5.2%), with no significant geographic differences (4.7%, 6.5%, and 2.5%, respectively; P =.08), with similar results in the Supreme DES group alone (4.4%, 6.8%, and 3.7%, respectively, P =.20). Cardiac death at 12 months occurred in 0.4%, 0.2%, and 0.0% (P =.79), target vessel-related myocardial infarction occurred in 2.2%, 4.7%, and 3.7%, (P =.10), and clinically driven target lesion revascularization was required in 2.1%, 3.1%, and 0%, respectively (P =.15). Compared with those from high-recruiting sites, results from low-recruiting sites were similar for target lesion failure, major adverse cardiac events, stent thrombosis, and mortality, with a nonsignificant trend for higher rates of myocardial infarction. Conclusions: Despite regional differences in patient characteristics, the clinical outcomes between Supreme DES and durable polymer everolimus-eluting stent in the PIONEER III trial were not different, supporting the generalizability and robustness of the findings from this multicenter controlled trial.

Impella Versus Intra-Aortic Balloon Pump for High-Risk PCI: A Propensity-Adjusted Large-Scale Claims Dataset Analysis.

Impella was approved by the Food and Drug Administration in 2015 for use during high-risk percutaneous coronary interventions (PCIs); however, its safety and efficacy compared with intra-aortic balloon pump (IABP) has not been evaluated in contemporary practice and remains debated. We aimed to compare postapproval outcomes and costs of Impella versus IABP support for high-risk PCI in real-world practice across hospitals in the United States. We identified patients from the Premier Healthcare Database undergoing nonemergent Impella- or IABP-supported high-risk PCI. We used propensity adjustment to control baseline, procedure, and post-PCI medical treatment differences between treatment groups. We included patients undergoing nonemergent single-PCI procedures with either Impella or IABP support and excluded patients presenting with acute ST-elevation myocardial infarction or cardiogenic shock or requiring >1 mechanical support devices during index hospitalization. Outcomes included in-hospital survival, myocardial infarction (MI), cardiogenic shock, stroke, bleeding requiring transfusion, acute kidney injury, index hospitalization length of stay, and costs. From April 2016 to June 2019, a total of 48,179 patients were treated with Impella or IABP mechanical circulatory support at 304 hospitals in the United States. Among these, we identified 2,156 patients undergoing nonemergent high-risk PCI treated with Impella (n = 1,447) or IABP (n = 709). After propensity adjustment, Impella use was associated with improved survival (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.02 to 2.36) and less MI (OR 0.29, 95% CI 0.18 to 0.46) and cardiogenic shock (OR 0.54, 95% CI 0.39 to 0.74). Stroke, bleeding requiring transfusion, and acute kidney injury were similar between groups. In conclusion, this Premier Healthcare Database propensity-adjusted analysis, Impella use during nonemergent high-risk PCI was associated with improved survival and reduced in-hospital MI and cardiogenic shock compared with IABP.

Outcomes of the Novel Supreme Drug-Eluting Stent in Complex Coronary Lesions: A PIONEER III Substudy.

Background: The Supreme healing-targeted drug-eluting stent (DES) is designed to promote endothelial healing to reduce stent-related adverse events. This may be particularly relevant among complex lesions that have a higher rate of adverse events. We sought to compare 1-year outcomes of percutaneous coronary intervention in complex lesions between the Supreme DES and contemporary durable-polymer, everolimus-eluting stents (DP-EES). Methods: PIONEER III was a multicenter, prospective, single-blind clinical trial, randomizing 1629 patients with either an acute or chronic coronary syndrome in a 2:1 ratio to the Supreme DES or DP-EES. Complex lesions (American College of Cardiology/American Heart Association type B2/C) were found in 1137 patients. Outcomes were also compared for specific parameters of lesion complexity: severe calcification, long length (>20 â€‹mm), and severe tortuosity. The primary end point was target lesion failure at 1 â€‹year. Results: At 1 â€‹year, there was no difference in target lesion failure between the Supreme DES and DP-EES: (5.7% vs 5.6%; hazard ratio 1.00, 95% confidence interval 0.59-1.68, P = .99). Similarly, there were no differences in the secondary end points of lesion success (99.7% vs 99.4%, P = .41), device success (97.0% vs 98.5%, P = .14), target vessel failure (6.5% vs 7.4%, P = .50), major adverse cardiac events (7.8% vs 8.5%, P = .64), or stent thrombosis (0.7% vs 1.1%, P = .48). A trend was observed toward a higher rate of target lesion revascularization with the Supreme DES (2.5% vs 0.9%, P = .06). Conclusions: This study suggests that the Supreme DES is as effective and safe at 1 â€‹year compared with the standard DP-EES across a broad spectrum of lesion complexity.

Safety and Efficacy of the Supreme Biodegradable Polymer Sirolimus-Eluting Stent in Patients With Diabetes Mellitus.

Background: Patients with diabetes mellitus (DM) have worse outcomes following percutaneous coronary intervention than nondiabetic patients. The novel Supreme DES is a biodegradable polymer sirolimus-eluting stent designed to synchronize early drug delivery, limiting the potential for long-term inflammatory response. The purpose of this study was to evaluate the safety and efficacy of the Supreme DES in patients with DM. Methods: This is a prespecified analysis of the diabetic subgroup from the PIONEER III randomized (2:1), controlled trial, comparing the Supreme DES with a durable polymer everolimus-eluting stent (DP-EES). The primary safety and efficacy composite endpoint was target lesion failure at 1 year, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Results: The PIONEER III trial randomized 1629 patients, of which 494 (30.3%) had DM with 331 (398 lesions) randomly assigned to Supreme DES and 163 (208 lesions) to DP-EES. Among patients with DM, target lesion failure at 1 year was 6.1% (20/331) with Supreme DES vs 3.7% (6/163) with DP-EES (hazard ratio = 1.65; 95% confidence interval = 0.66-4.10, P = .28). The composite of cardiac death or target vessel myocardial infarction was 3.3% (11/331) with Supreme DES and 3.7% (6/163) with DP-EES (hazard ratio = 0.90; 95% confidence interval = 0.33-2.44, P = .83). There were no significant differences in other secondary endpoints. Conclusions: This prespecified substudy of the PIONEER III trial demonstrated the relative safety and efficacy of the novel Supreme DES when compared with commercially available DP-EES in diabetics at 1 year. Longer term follow-up will be required to ensure continued safety and efficacy of the Supreme DES.

Comparison between ticlopidine and clopidogrel in patients undergoing primary stenting in acute myocardial infarction: results from the CADILLAC trial.

OBJECTIVE: The aim of this article is to examine whether clopidogrel and ticlopidine treatments produce similar clinical outcomes for patients receiving primary stenting for acute myocardial infarction (AMI). BACKGROUND: Prior studies have yielded conflicting results on the relative safety and efficacy of clopidogrel and ticlopidine after stent implantation, warranting an evaluation in primary stenting for AMI. METHODS: In the multicenter, prospective CADILLAC trial, patients undergoing primary infarct stenting were treated at operator discretion with either ticlopidine (931 patients) or clopidogrel (163 patients) and then followed for 1 year. Baseline clinical and angiographic characteristics were comparable except for baseline TIMI 0/1 flow (72.5% clopidogrel vs. 63.9% ticlopidine, P = 0.04). RESULTS: Patients receiving clopidogrel had more recurrent ischemia in hospital (6.1 vs. 2.8%, P = 0.02) and at 30 days (10.5 vs. 5.8%, P = 0.02), more moderate and severe bleeding at 30 days (7.4 vs. 2.7%, P = 0.002), and similar rates of stent thrombosis out to 1 year (P = 0.11). By multivariable analysis, clopidogrel use was an independent predictor for recurrent ischemia in hospital (P = 0.0002), and at 30 days (P = 0.012); and of moderate and severe bleeding in hospital (P = 0.002), and at 30 days (P = 0.001). CONCLUSIONS: Despite thienopyridines similarities, their efficacy may be different within the first 30 days of primary stenting for AMI. A prospective, randomized trial is required to confirm these findings.

Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

BACKGROUND: Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown. METHODS AND RESULTS: In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P<0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P=0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P<0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (P=0.01) and in ischemic TVR from 20.4% to 10.8% (P=0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. CONCLUSIONS: The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.

Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professionals from the American Heart Association.

More than 1.2 million percutaneous coronary interventions are performed annually in the United States, with only an estimated 33% performed in women, despite the established benefits of percutaneous coronary intervention and adjunctive pharmacotherapy in reducing fatal and nonfatal ischemic complications in acute myocardial infarction and high-risk acute coronary syndromes. This statement reviews sex-specific data on the safety and efficacy of contemporary interventional therapies in women.

Treatment of coronary artery perforations complicating percutaneous coronary intervention with a polytetrafluoroethylene-covered stent graft.

Coronary artery perforation is a rare, but dreaded, complication of percutaneous coronary intervention. Conventional treatment, including reversal of anticoagulation and prolonged balloon inflation, is associated with a high incidence of death, Q-wave myocardial infarction, and emergency coronary bypass surgery. Although a number of case reports have demonstrated the feasibility of sealing coronary perforations with synthetic material-covered stent grafts, the efficacy of this treatment has not been reported in a large, multicenter series. We used a retrospective international registry to examine the outcomes of the polytetrafluoroethylene-coated JOSTENT coronary stent graft (CSG) in 41 cases of coronary perforations. Perforations were relatively severe: 16.7% Ellis grade 1, 54.2% grade 2, and 29.1% grade 3. Of the 41 patients, > 1/3 (n = 14) experienced life-threatening complications before stent graft implantation, including pericardial tamponade (12.2%), cardiogenic shock (9.8%), and cardiac arrest (2.4%). A total of 52 CSGs were used to treat the 41 perforations (mean 1.3 per lesion). All CSGs were placed successfully, with 92.9% of the perforations sealed completely and 7.1% partially. One patient developed abrupt vessel closure after CSG deployment, resulting in an overall procedure success rate of 96.4%. No in-hospital Q-wave myocardial infarctions, emergency coronary bypass surgeries, or deaths resulted. The CSG may be a reliable and highly effective treatment option for sealing coronary perforations complicating percutaneous coronary interventions.