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Purpose of Review The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. The outcome trials have yielded highly inconsistent results, perhaps attributable to variations in dosage, formulation, and composition. In particular, CV trials using icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reproducibly reduced CV events and progression of atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence for differences among n3-FAs on the development and manifestations of atherothrombotic disease. Recent Findings Large randomized clinical trials with n3-FAs have produced discordant outcomes despite similar patient profiles, doses, and triglyceride (TG)-lowering effects. A large, randomized trial with IPE, a prescription EPA only formulation, showed robust reduction in CV events in statin treated patients in a manner proportional to achieved blood EPA concentrations. Multiple trials using mixed EPA/DHA formulations have not shown such benefits, despite similar TG lowering. These inconsistencies have inspired investigations into mechanistic differences among n3-FAs, as EPA and DHA have distinct membrane interactions, metabolic products, effects on cholesterol efflux, antioxidant properties, and tissue distribution. EPA maintains normal membrane cholesterol distribution, enhances endothelial function, and in combination with statins improves features implicated in plaque stability and reduces lipid content of plaques. Summary Insights into reductions in residual CV risk have emerged from clinical trials using different formulations of n3-FAs. Among high-risk patients on contemporary care, mixed n3-FA formulations showed no reduction in CV events. The distinct benefits of IPE in multiple trials may arise from pleiotropic actions that correlate with on-treatment EPA levels beyond TG-lowering. These effects include altered platelet function, inflammation, cholesterol distribution, and endothelial dysfunction. Elucidating such mechanisms of vascular protection for EPA may lead to new interventions for atherosclerosis, a disease that continues to expand worldwide.

BACKGROUND: The goal of this work was to investigate trends (2001–2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects. METHODS: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643 800 matched control subjects. Incident outcomes comprised coronary artery disease, acute myocardial infarction, cerebrovascular disease, and heart failure (HF). Trends in time to first event for each outcome were analyzed with Cox regression and standardized incidence rates. In the group with T2D, Cox regression was also used to assess risk factor levels beyond target and outcomes, as well as the relative importance of each risk factor to each model. RESULTS: Among individuals with T2D, incidence rates per 10 000 person-years in 2001 and 2019 were as follows: acute myocardial infarction, 73.9 (95% CI, 65.4–86.8) and 41.0 (95% CI, 39.5–42.6); coronary artery disease, 205.1 (95% CI, 186.8–227.5) and 80.2 (95% CI, 78.2–82.3); cerebrovascular disease, 83.9 (95% CI, 73.6–98.5) and 46.2 (95% CI, 44.9–47.6); and HF, 98.3 (95% CI, 89.4–112.0) and 75.9 (95% CI, 74.4–77.5). The incidence for HF plateaued around 2013, a trend that then persisted. In individuals with T2D, glycated hemoglobin, systolic blood pressure, estimated glomerular filtration rate, and lipids were independently associated with outcomes. Body mass index alone potentially explained >30% of HF risk in T2D. For those with T2D with no risk factor beyond target, there was no excess cardiovascular risk compared with control subjects except for HF, with increased hazard with T2D even when no risk factor was above target (hazard ratio, 1.50 [95% CI, 1.35–1.67]). Risk for coronary artery disease and cerebrovascular disease increased in a stepwise fashion for each risk factor not within target. Glycated hemoglobin was most prognostically important for incident atherosclerotic events, as was body mass index for incident of HF. CONCLUSIONS: Risk and rates for atherosclerotic complications and HF are generally decreasing among individuals with T2D, although HF incidence has notably plateaued in recent years. Modifiable risk factors within target levels were associated with lower risks for outcomes. This was particularly notable for systolic blood pressure and glycated hemoglobin for atherosclerotic outcomes and body mass index for heart failure.

Introduction: An increasing number of patients with acute ischemic stroke (AIS) have recently used non-vitamin K antagonist oral anticoagulants (NOACs). However, there are limited data on safety of endovascular therapy (EVT) in these patients. Methods: We performed a retrospective, observational, cohort study of patients treated with EVT within 6 hours of symptom onset in the American Heart Association’s “Get With The Guideline-Stroke Program” between October 2015 and March 2020 to compare safety and functional outcomes in patients who were or were not taking NOACs in the 7 days prior to stroke. Results: Of 33,355 patients (median age 72 years (60,81); 50.8% female), 3,727 (11.2%) were taking NOACs, and 29,628 (88.8%) were not taking any oral anticoagulants (OAC) prior to stroke. Compared with those not on OAC, patients taking NOACs were older (median age 75 vs. 71 years) and had a higher prevalence of comorbidities including cardiovascular risk factors, although stroke severity was similar between the groups (median NIHSS 18 vs. 17). After adjusting for baseline clinical factors including intravenous alteplase, patients taking NOACs were not at a significantly higher risk of sICH compared with patients not taking anticoagulants (4.9% vs 6.4%; aOR, 0.93 [95% CI, 0.75-1.14]) or in-hospital mortality (14.1% vs 13.1%; aOR, 0.90 [95% CI, 0.78-1.02]). Of the secondary discharge outcomes, 3 of 7 showed significant differences in favor of the NOAC group including ambulating independently (33.7% vs 38.7%; aOR, 1.15 [95% CI, 1.02-1.30]) and freedom from disability (modified Rankin Scale [mRS] 0-1, 13.0% vs 16.2%; aOR, 1.23 [95% CI, 1.04-1.46]) at discharge. In a subset of patients with documented time of last NOACs dose (n=213), sICH rate was 3.1% (6/196) with last dose ≤2 days and 0% (0/17) with >2 days. Conclusions: Among patients with acute ischemic stroke treated with EVT within 6 hours, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of adverse events and was associated with better functional outcomes at discharge.

Introduction: Emergent endovascular thrombectomy (EVT) is effective in improving outcomes in patients with stroke caused by large vessel occlusion. However, there are limited data on the use of EVT in patients taking an oral vitamin K antagonist (VKA), constraining guideline development around EVT use in this vulnerable population. Methods: To address this knowledge gap, we performed a retrospective, observational, cohort study based on a population-based sample of stroke admissions in the US (the AHAs “Get With The Guidelines-Stroke" Program) between October 2015 and March 2020. We aimed to determine whether use of VKA was associated with the risk of symptomatic intracranial hemorrhage (sICH) and functional outcomes in patients undergoing EVT within 6 hours of time last known well after adjusting for pre-specified confounders. Results: Of 32,715 patients (median age 72 years; 50.7% female), 3,087 were taking a VKA and 29,628 were not on an OAC prior to stroke. Patients taking VKAs were older (median age 78 vs. 71 years) but stroke severity was similar between the groups (median NIHSS 18 vs. 17). Of patients taking a VKA, 211 (6.8%) suffered a sICH whereas 1,904 (6.4%) patients not on OAC developed a sICH. VKA was not associated with sICH (adjusted odds ratio 1.20, 95% CI: 0.96-1.49). VKA use was associated with a higher risk of life-threatening systemic hemorrhage (1.2% vs. 1.02%; aOR 1.93 (1.17-3.19)) but not with mortality/discharge to hospice (27.1% vs. 20.6%; aOR 1.02 (0.90-1.14)). Patients taking a VKA prior to EVT were more likely to be able to be ambulatory at discharge (aOR 1.24 [1.11-1.39]) and to have an mRS of 0-2 (aOR 1.23 [1.07-1.42]). Conclusions: Among patients with acute ischemic stroke on VKA, EVT appears to be well tolerated without prohibitive risks of sICH. Our results provide support for the deployment of this critical, disability-reducing therapy in this population of patients with a large vessel occlusion presenting within 6 hours of time last known well.

Aims Cigarette smoking is among the most well-established risk factors for adverse cardiovascular outcomes. We sought to determine whether icosapent ethyl (IPE), a highly purified form of eicosapentaenoic acid with antiatherothrombotic properties, may reduce the excessive risk of cardiovascular disease (CVD) attributable to smoking. Methods and results Reduction of Cardiovascular Events with Icosapent Ethyl Trial (REDUCE-IT) was a multinational, double-blind trial that randomized 8179 statin-treated patients with elevated triglycerides and CV risk to IPE or placebo, with a median follow-up period of 4.9 years. Icosapent ethyl reduced the primary composite endpoint [CV death, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, or hospitalization for unstable angina] by 25% (P Conclusion In REDUCE-IT, IPE treatment was associated with a reduced risk of CV events in current and former smokers to levels observed in never smokers. While smoking cessation should always be recommended, these data raise the possibility that IPE treatment may attenuate CV hazards attributable to smoking.

Background: The Reduction of Cardiovascular Events with Icosapent Ethyl (IE)-Intervention Trial (REDUCE-IT) demonstrated the efficacy of IE among patients with elevated triglyceride levels despite the use of statins. This study aimed to examine the cost-effectiveness (CE) of IE among US adults using both in-trial and lifetime time horizons. Methods: US patients in REDUCE-IT were included in the in-trial analysis. We included all cardiovascular and serious adverse events from the REDUCE-IT database where rates differed between the study arms; we used patient-level data from REDUCE-IT USA based on 2019 US costs and $4.16/day for IE. The lifetime analysis used a microsimulation Markov model. Both analyses considered value from a US health sector perspective. The primary result is the incremental CE ratio (ICER), measured as incremental costs divided by incremental quality-adjusted life-years (QALY) of IE compared with placebo. We performed univariate and probabilistic sensitivity analyses (PSA) to capture the uncertainties involved in the estimation of costs and QALYs. Results: Based on 3146 REDUCE-IT USA participants, there was an incremental gain in QALYs with IE compared with placebo using in-trial (3.28 vs. 3.13) and lifetime (10.36 vs. 9.83) time horizons. Total healthcare costs were lower with IE compared with placebo for both in-trial ($20,221 vs. $20,357) and lifetime ($201,842 vs. $204,701). IE was a dominant strategy compared to placebo using a lifetime time horizon with a 74.8% probability of being more effective and costing less and had a 99.6% probability of costing below $50,000 per QALY. The lifetime PSA showed that IE was a dominant strategy in 65.6% of simulations and cost-effective in 98.8%, 99.6%, and 99.9% of simulations at the $50,000, $100,000, and $150,000 per QALY gained thresholds, respectively. Conclusions: The REDUCE-IT USA cost-effectiveness analysis has shown that IE provides better outcomes with lower costs, dominant both in-trial and lifetime as well in the majority of sensitivity analyses and subgroups, both in primary and secondary prevention. These results, with the clinical evidence of efficacy, suggest that at $4.16 per day, IE therapy should be strongly considered in patients similar to those enrolled in REDUCE-IT USA.

Dietary interventions may best be delivered at grocery stores, which offer convenience, accessibility, full food inventories, and increasingly, in-store registered dietitians, online shopping, and delivery services. In collaboration with a large supermarket chain, we conducted a multisite, randomized, controlled trial (N = 247) of two individualized, in-person, dietitian-led, purchasing data-guided, education interventions focused on increasing Dietary Approaches to Stop Hypertension (DASH) score (a measure of DASH dietary pattern adherence). At both 3 and 6 months, all study groups had greater DASH adherence. At 3 months, the interventions increased DASH score by 4.7 (95% CI, 0.9, 8.5; p = 0.02), compared with the enhanced control group. In addition, the intervention that included online enhancements (e.g. online shopping, nutrition applications) increased DASH score by 3.8 (95% CI, 0.8, 6.9; p = 0.01) compared to the one without them. This trial demonstrates the efficacy of store-based, dietary interventions as well as modern online shopping tools in increasing DASH adherence.

Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after 1 January 2010 and were active during the period from 1 January 2015 to 31 December 2020. The effect of the pandemic period on non-COVID-19 trials was determined by piece-wise regression models using 11 March 2020 as the start of the pandemic and by time series analysis (models fitted using 2015–2018 data and forecasted for 2019–2020). The study endpoints were early trial stoppage, normal trial completion, and trial activation. There were 161,377 non-COVID-19 trials analyzed. The number of active trials increased annually through 2019 but decreased in 2020. According to the piece-wise regression models, trial completion was not affected by the pandemic (p = 0.56) whereas trial stoppage increased (p = 0.001). There was a pronounced decrease in trial activation early during the pandemic (p < 0.001) which then recovered. The findings from the time series models were consistent comparing forecasted and observed results (trial completion p = 0.22; trial stoppage p < 0.01; trial activation, p = 0.01). During the pandemic, there was an increase in non-COVID-19 RCTs stoppage without changes in RCT completion. There was a sharp decline in new RCTs at the beginning of the pandemic, which later recovered.

Introduction: Endoscopic Vein Harvesting (EVH) provides comparable rates in major adverse cardiac events to Open Vein Harvest (OVH) based on the intermediate-term results of the REGROUP Trial. Value based purchasing places more pressure to examine whether minimally invasive techniques, e.g., EVH, yield intended or unintended economic effects. The objective of this study was to compare health care costs between participants randomized to EVH or OVH during coronary artery bypass graft (CABG) surgery in the REGROUP trial. Hypothesis: We hypothesized that EVH would result in lower discharge and follow-up costs compared to the traditional OVH. Methods: Department of Veterans Affairs Cooperative Studies Program #588 (Clinicaltrials.gov NCT01850082) randomized 1150 participants (574 OVH, 576 EVH) at 16 VA medical centers. We linked participants to VA administrative data in VA’s Corporate Data Warehouse and extracted activity-based cost data starting with the index surgery. We analyzed discharge costs for the index surgery as well as follow-up costs in 30-day periods for EVH vs. OVH, comparing results from different statistical models to test for robustness. All costs were standardized to 2020 US dollars. Results: The unadjusted average cost for CABG patients with EVH and OVH was $76,607 (SD $43,883) and $75,368 (SD $45,900), respectively; the costs include both facility and provider costs. Despite the skewed variation in costs, there were no significant differences in discharge costs and high-cost patients were equally likely in both groups. We also found no significant differences in follow-up costs; the average follow-up period was 33 months (maximum follow-up was 85 months). The results were highly robust to the statistical model. Conclusions: Endoscopic harvesting was not associated with a reduction in costs for the index CABG surgery or follow-up care, nor was it associated with increased costs through unintended events. Therefore, the choice to provide endoscopic harvesting should be based on surgeon and patient preferences.

Tracheal access, accidental deccannulation, peristomal granulation, stenosis and difficult weaning are the laryngologist’s dilemma, wherever tracheostomy has been resorted to, in the paediatric age group. These major problems necessitate a modification in the procedure of tracheostomy where ‘stay’ and ‘maturation’ sutures are utilized. The stay sutures facilitate a quick midline tracheotomy and the maturation ones minimise parastomal granulation and easy tracheal recannulation.

The aim of this study was to examine real-world experience with repeat transcatheter aortic valve replacement (TAVR) in a population-based national database.Repeat TAVR is a growing option in patients requiring reintervention for TAVR. However, large-scale studies with longitudinal follow-up are limited.All Medicare beneficiaries who underwent TAVR from 2012 to 2017 were included. Outcomes included 30-day and longitudinal mortality and major adverse cardiovascular events, defined as death, stroke, pacemaker insertion, major bleeding, acute kidney injury, or cardiac arrest. Outcomes of repeat TAVR were compared with surgical explantation after TAVR (TAVR explantation) in a matched analysis.Of 133,250 patients who underwent TAVR, 617 (0.46%) underwent subsequent repeat TAVR at a median interval of 154 days (interquartile range: 58-537 days). Mortality at 30 days and 1 year was 6.0% and 22.0%, respectively. Rates of 30-day stroke and pacemaker insertion were 1.8% and 4.2%. Mortality at 30 days was lower in those who underwent their first TAVR during the later era (2015-2017) compared with earlier years (2012-2014) (4.6% vs 8.7%; P = 0.049). Repeat TAVR was associated with lower 30-day mortality compared with a matched group undergoing TAVR explantation (6.2% vs 12.3%; P = 0.05), although 1-year mortality was similar (21.0% vs 20.8%; P = 1.000). The incidence of 30-day major adverse cardiovascular events was higher with TAVR explantation compared with repeat TAVR (risk ratio: 2.92; 95% CI: 1.88-4.99; P ≤ 0.001).Repeat TAVR was performed with acceptable 30-day mortality in this high-risk population. Short-term outcomes were superior to surgical explantation, but 1-year outcomes were similar. Repeat TAVR will likely be an important option for aortic valve reintervention after TAVR.

The great toll the COVID-19 pandemic had on healthcare workers highlights the need to improve the working environment in hospitals. This is especially true in procedure rooms such as operating and delivery rooms, which inherently require extended exposure to the virus, allow no social distancing, and generate aerosolized virus through the equipment. Therefore, strategies must be created to address these issues. Such a strategy includes calculating and implementing air exchanges per hour with the use of Heating, Ventilation, and Air Conditioning Systems (HVAC). HVAC allows the exchange of air within the procedure room, reducing the amount of exposure to viruses, and resulting in safer working environments for healthcare workers.8,9 Though HVAC creates a safer working environment, there remains a need to create a more cost-effective, efficient system. However, it is imperative to continue improving this system because there will be more pandemics where such a system will save many lives.

Purpose: To identify changes in superficial retinal capillary microvasculature before and after cataract surgery using optical coherence tomography angiography (OCTA). Setting: Rajan eye care, Tertiary care center in Chennai, India. Design: Prospective observational study. Methods: Patients above 40 years who underwent uncomplicated cataract surgery had 6 × 6 mm OCTA foveacentered scans using Zeiss Angioplex 5000 OCTA before and 4 weeks postoperatively. Signal strength and automated values obtained for perfusion density (PD) and vascular density (VD) were recorded. Results: Fifty-eight eyes of 33 patients aged 67 ± 5 years were enrolled. Signal strength (3.9 ± 2.3 vs. 5.7 ± 2.1, p

Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events.We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06).Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).