Carotid Artery Stenting Using a Novel Self-Expanding Braided Nickel–Titanium Stent: Feasibility and Safety Porcine Trial

We studied the deliverability and safety of a braided, self-expanding, closed-cell nickel–titanium (NiTi) stent (E-volution, Jotec GmbH, Hechingen, Germany) especially designed for the endovascular treatment of carotid artery bifurcation stenosis with special regard to in-stent stenosis and thrombosis compared with a laser-cut reference nitinol stent in a porcine model of percutaneous vascular interventions. We aimed to assess histopathologic response in minipig carotid and subclavian arteries. Eight minipigs received a total of 42 stents: 14 reference stents and 28 E-volution stents. Eleven of the E-volution stents were additionally coated with heparin. Control angiography was obtained immediately before and after vascular intervention as well as 4 weeks after the procedure. Primary endpoints were 28 days of angiographic analyses as well as histomorphometric analysis, including injury score, inflammation score, luminal diameter, vessel diameter, maximal neointimal thickness, and area of in-stent stenosis. Secondary end points were procedural success, 28-day mortality, and stent thrombosis. All stents could be delivered successfully without procedural complications, morbidity, or mortality during our observation time. As confirmed by histology, no in-stent thrombosis was observed. Compared with common carotid arteries, subclavian arteries are significantly more vulnerable to developing in-stent stenosis caused by neointima proliferation (p < 0.05). Compared with the use of 1 single stent/artery, serial application of two stents leads to a more excessive but not significantly different neointimal proliferation (p > 0.05). The E-volution stent, especially when heparin coated, is in line with the comparison to the laser-cut reference stent displaying similar results of angiographic, histologic, and histomorphometric analyses (p > 0.05). Compared with the reference laser-cut stent, the self-expanding nitinol stent (E-volution) with its advanced braiding technology is feasible and safe. In our opinion, the high radial resistive force and the advanced braided design with tight stent-strut interstices may be beneficial in terms of plaque stabilization. Further studies are necessary and warranted

Insights into the pathogenesis of vein graft disease: lessons from intravascular ultrasound

The success of coronary artery bypass grafting (CABG) is limited by poor long-term graft patency. Saphenous vein is used in the vast majority of CABG operations, although 15% are occluded at one year with as many as 50% occluded at 10 years due to progressive graft atherosclerosis. Intravascular ultrasound (IVUS) has greatly increased our understanding of this process. IVUS studies have shown that early wall thickening and adaptive remodeling of vein grafts occurs within the first few weeks post implantation, with these changes stabilising in angiographically normal vein grafts after six months. Early changes predispose to later atherosclerosis with occlusive plaque detectable in vein grafts within the first year. Both expansive and constrictive remodelling is present in diseased vein grafts, where the latter contributes significantly to occlusive disease. These findings correlate closely with experimental and clinicopathological studies and help define the windows for prevention, intervention or plaque stabilisation strategies. IVUS is also the natural tool for evaluating the effectiveness of pharmacological and other treatments that may prevent or slow the progression of vein graft disease in clinical trials

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Author Manuscript: 2011 April 14Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.National Institutes of Health (U.S.) (GM 49039

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Several clinical studies have identified a strong correlation between neointimal hyperplasia following coronary stent deployment and both stent-induced arterial injury and altered vessel hemodynamics. As such, the sequential structural and fluid dynamics analysis of balloon-expandable stent deployment should provide a comprehensive indication of stent performance. Despite this observation, very few numerical studies of balloon-expandable coronary stents have considered both the mechanical and hemodynamic impact of stent deployment. Furthermore, in the few studies that have considered both phenomena, only a small number of stents have been considered. In this study, a sequential structural and fluid dynamics analysis methodology was employed to compare both the mechanical and hemodynamic impact of six balloon-expandable coronary stents. To investigate the relationship between stent design and performance, several common stent design properties were then identified and the dependence between these properties and both the mechanical and hemodynamic variables of interest was evaluated using statistical measures of correlation. Following the completion of the numerical analyses, stent strut thickness was identified as the only common design property that demonstrated a strong dependence with either the mean equivalent stress predicted in the artery wall or the mean relative residence time predicted on the luminal surface of the artery. These results corroborate the findings of the large-scale ISAR-STEREO clinical studies and highlight the crucial role of strut thickness in coronary stent design. The sequential structural and fluid dynamics analysis methodology and the multivariable statistical treatment of the results described in this study should prove useful in the design of future balloon-expandable coronary stents

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402