Efficacy of Pemafibrate Versus Fenofibrate Administration on Serum Lipid Levels in Patients with Dyslipidemia: Network Meta-Analysis and Systematic Review.

BACKGROUND: Pemafibrate is a novel fibrate class drug that is a highly potent and selective agonist of peroxisome proliferator-activated receptor α (PPARα). We performed the first ever network meta-analysis containing the largest ever group of patients to test the efficacy of pemafibrate in improving lipid levels compared with fenofibrate and placebo in patients with dyslipidemia. METHODS: Potentially relevant clinical trials were identified in Medline, PubMed, Embase, clinicaltrials.gov, and Cochrane Controlled Trials registry. Nine randomized controlled trials met the inclusion criteria out of 40 potentially available articles. The primary effect outcome was a change in the levels of triglycerides (TG), high-density lipoproteins (HDL), or low-density lipoproteins (LDL) before and after the treatment. RESULTS: A total of 12,359 subjects were included. The mean patient age was 54.73 (years), the mean ratio for female patients was 18.75%, and the mean examination period was 14.22 weeks. The dose for pemafibrate included in our study was 0.1, 0.2, or 0.4 mg twice daily, whereas the dose for fenofibrate was 100 mg/day. Data showed a significant reduction in TG and a mild increase in HDL levels across the pemafibrate group at different doses and fenofibrate 100 mg group (with greatest effect observed with pemafibrate 0.1 mg twice daily). A mild increase in LDL was also observed in all groups, but the increase in LDL in the 0.1 mg twice daily dose group was statistically insignificant. CONCLUSION: Pemafibrate 0.1 mg twice daily dose led to highest reduction in TG levels and the highest increase in HDL levels compared with other doses of pemafibrate, fenofibrate, and placebo.

Cardiovascular Outcomes of Older versus Newer Generation Transcatheter Aortic Valve Replacement Recipients: A Systematic Review & Meta-analysis.

Newer generation transcatheter heart valves (THV) are presumed to yield better clinical efficacy and postprocedural complication profile as compared to transcatheter aortic valve replacement (TAVR) using older generation THVs. The real impact of newer generation valves on TAVR outcomes is not well known. Studies comparing older and newer generation THVs were identified from online databases including PubMed, EMBASE, Cochrane, and ClinicalTrials.gov from inception until August 2020. The primary outcome of the study was to compare mortality. Secondary outcomes included cerebrovascular events, myocardial infarction, major vascular complications, major bleeding, acute kidney injury, paravalvular leak, and post-procedural pacemaker implantation. Statistical analysis was performed using the Mantel-Haenszel random effect model with an odds ratio (OR), 95% confidence interval (CI), and p-value significance ≤0.05. A total of 14 studies were included with a combined patient population of 5697 patients (older generation n=1996; newer generation n=3701). Newer generation valves showed statistically significant results favoring lower major vascular complications (OR=2.05; 95% CI, 1.33-3.18; P = 0.00), major bleeding (OR=1.99; 95% CI, 1.35-2.93; P = 0.00), acute kidney injury (OR=1.71; 95% CI, 1.13-2.59; P = 0.01), paravalvular leak (OR=2.41; 95% CI, 1.11-5.28; P = 0.03) and mortality (OR=1.50; 95% CI, 1.10-2.06; P = 0.01) as compared to older generation valves. Cerebrovascular events, myocardial infarction, and pacemaker placement rates were found to be similar between older and newer generation valves. TAVR outcomes using newer generation valves are superior to those of older generation valves in terms of major vascular complications, acute kidney injury, paravalvular leak, and mortality.

Comparison of In-Hospital Outcomes After Insertion of Watchman Device in Men Versus Women (from the National Inpatient Data).

Left atrial appendage occlusion with the Watchman device is approved to manage nonvalvular atrial fibrillation and prevent stroke in patients with contraindications to anticoagulation. This study aimed to analyze the National Inpatient Sample (NIS) data to evaluate gender disparities and further assess its impact on medical decision-making. The NIS data for 16,505 patients who underwent left atrial appendage occlusion with the Watchman device from 2016 to 2017 was used to perform a cross-sectional analysis. The primary end point was risk-adjusted in-hospital mortality. The study included 9,825 men and 6,680 women. Male patients were younger than female patients (mean age of 75.3 years vs 76.3 years, p <0.001). The observed in-hospital mortality was higher in female patients (0.3% vs 0.1%, p = 0.003). This remained significant after adjustment for baseline confounders (adjusted odds ratio 2.9, 95% confidence interval 1.4 to 6.3, p = 0.005). In conclusion, analysis of the large pool of NIS data reveals that female patients have relatively worse in-hospital outcomes in terms of mortality, length of stay, and total hospitalization cost than male patients who underwent Watchman device implantation. However, these disparities are not enough to impact the medical decision-making process and to defer the use of the Watchman device in female patients.

Clinical characteristics and outcomes of patients with Corona Virus Disease 2019 (COVID-19) at Mercy Health Hospitals, Toledo, Ohio.

IMPORTANCE: The ongoing pandemic of the novel Corona Virus Disease 2019 (COVID-19) is an unprecedented challenge to global health, never experienced before. OBJECTIVE: This study aims to describe the clinical characteristics and outcomes of patients with COVID-19 admitted to Mercy Hospitals. DESIGN AND METHODS: Retrospective, observational cohort study designed to include every COVID-19 subject aged 18 years or older admitted to Mercy Saint (St) Vincent, Mercy St Charles, and Mercy St Anne's hospital in Toledo, Ohio from January 1, 2020 through June 15th, 2020. Primary Outcome Measure was mortality in the emergency department or as an in-patient. RESULTS: 470 subjects including 224 males and 246 females met the inclusion criteria for the study. Subjects with the following characteristics had higher odds (OR) of death: Older age [OR 8.3 (95% CI 1.1-63.1, p = 0.04)] for subjects age 70 or more compared to subjects age 18-29); Hypertension [OR 3.6 (95% CI 1.6-7.8, p = 0.001)]; Diabetes [OR 3.1 (95% CI 1.7-5.6, p<0.001)]; COPD [OR 3.4 (95% CI 1.8-6.3, p<0.001)] and CKD stage 2 or greater [OR 2.5 (95% CI 1.3-4.9, p = 0.006)]. Combining all age groups, subjects with hypertension had significantly greater odds of the following adverse outcomes: requiring hospital admission (OR 2.2, 95% CI 1.4-3.4, p<0.001); needing respiratory support in 24 hours (OR 2.5, 95% CI: 1.7-3.7, p<0.001); ICU admission (OR 2.7, 95% CI 1.7-4.4, p<0.001); and death (OR 3.6, 95% CI 1.6-7.8, p = 0.001). Hypertension was not associated with needing vent in 24 hours (p = 0.07). CONCLUSION: Age and hypertension were associated with significant comorbidity and mortality in Covid-19 Positive patients. Furthermore, people who were older than 70, and had hypertension, diabetes, COPD, or CKD had higher odds of dying from the disease as compared to patients who hadn't. Subjects with hypertension also had significantly greater odds of other adverse outcomes.

Does Pulmonary Embolism in Critically Ill COVID-19 Patients Worsen the In-Hospital Mortality: A Meta-Analysis.

BACKGROUND: Mortality in critically ill COVID (coronavirus disease) patients secondary to pulmonary embolism (PE) has conflicting data. We aim to evaluate the mortality outcomes of critically ill patients with and without PE (WPE). METHODS: Three studies were identified after a digital database search on PE in ICU (intensive care unit) patients until September 2020. The primary outcome was mortality. Outcomes were compared using a random method odds ratio and confidence interval of 95%. RESULTS: A total of 439 patients were included in the study. Diabetes, hypertension, and renal replacement requirement had no statistically significant association between PE and WPE, p = 0.39, p = 0.23, and p = 0.29 respectively. The study revealed that males have higher odds of PE, OR-1.98, 95%CI-1.01-3.89; p = 0.05. In-hospital mortality results were comparable between PE and WPE after subgroup analysis and correction of heterogeneity, p = 0.25. CONCLUSION: PE in critically ill COVID patients had similar in-hospital mortality outcomes as WPE patients. The findings are only hypotheses generated from observational studies and need future randomized, prospective clinical trials for a definitive conclusion.

Medical therapy vs early revascularization in diabetics with chronic total occlusions: A meta-analysis and systematic review.

BACKGROUND: Management of chronic total occlusions (CTO) in diabetics is challenging, with a recent trend towards early revascularization [ER: Percutaneous coronary intervention (PCI) and bypass grafting] instead of optimal medical therapy (OMT). We hypothesize that ER improves morbidity and mortality outcomes in diabetic patients with CTOs as compared to OMT. AIM: To determine the long term clinical outcomes and to compare morbidity and mortality between OMT and ER in diabetic patients with CTOs. METHODS: Potentially relevant published clinical trials were identified in Medline, Embase, chemical abstracts and Biosis (from start of the databases till date) and pooled hazard ratios (HR) computed using a random effects model, with significant P value < 0.05. Primary outcome of interest was all-cause death. Secondary outcomes included cardiac death, prompt revascularization (ER) or repeat myocardial infarction (MI). Due to scarcity of data, both Randomized control trials and observational studies were included. 4 eligible articles, containing 2248 patients were identified (1252 in OMT and 1196 in ER). Mean follow-up was 45-60 mo. RESULTS: OMT was associated with a higher all-cause mortality [HR: 1.70, 95% confidence interval (CI): 0.80-3.26, P = 0.11] and cardiac mortality (HR: 1.68, 95%CI: 0.96-2.96, P = 0.07). Results were close to significance. The risk of repeat MI was almost the same in both groups (HR: 0.97, 95%CI: 0.61-1.54, P = 0.90). Similarly, patients assigned to OMT had a higher risk of repeat revascularization (HR: 1.62, 95%CI: 1.36-1.94, P < 0.00001). Sub-group analysis of OMT vs PCI demonstrated higher all-cause (HR: 1.98, 95%CI: 1.36-2.87, P = 0.0003) and cardiac mortality (HR: 1.87, 95%CI: 0.96-3.62, P = 0.06) in the OMT group. The risk of repeat MI was low in the OMT group vs PCI (HR: 0.53, 95%CI: 0.31-0.91, P = 0.02). Data on repeat revascularization revealed no difference between the two (HR: 1.00, 95%CI: 0.52-1.93, P = 1.00). CONCLUSION: In diabetic patients with CTO, there was a trend for improved outcomes with ER regarding all-cause and cardiac death as compared to OMT. These findings were reinforced with statistical significance on subgroup analysis of OMT vs PCI.

Early intervention or watchful waiting for asymptomatic severe aortic valve stenosis: a systematic review and meta-analysis.

BACKGROUND: The management of patients with severe but asymptomatic aortic stenosis is challenging. Evidence on early aortic valve replacement (AVR) versus symptom-driven intervention in these patients is unknown. METHODS: Electronic databases were searched, articles comparing early-AVR with conservative management for severe aortic stenosis were identified. Pooled adjusted odds ratio (OR) was computed using a random-effect model to determine all-cause and cardiovascular mortality. RESULTS: A total of eight studies consisting of 2201 patients were identified. Early-AVR was associated with lower all-cause mortality [OR 0.24, 95% confidence interval (CI) 0.13-0.45, P ≤ 0.00001] and cardiovascular mortality (OR 0.21, 95% CI 0.06-0.70, P = 0.01) compared with conservative management. The number needed to treat to prevent 1 all-cause and cardiovascular mortality was 4 and 9, respectively. The odds of all-cause mortality in a selected patient population undergoing surgical AVR (SAVR) (OR 0.16, 95% CI 0.09-0.29, P ≤ 0.00001) and SAVR or transcatheter AVR (TAVR) (OR 0.53, 95% CI 0.35-0.81, P = 0.003) were significantly lower compared with patients who are managed conservatively. A subgroup sensitivity analysis based on severe aortic stenosis (OR 0.24, 95% CI 0.11-0.52, P = 0.0004) versus very severe aortic stenosis (OR 0.20, 95% CI 0.08-0.51, P = 0.0008) also mirrored the findings of overall results. CONCLUSION: Patients with asymptomatic aortic valve stenosis have lower odds of all-cause and cardiovascular mortality when managed with early-AVR compared with conservative management. However, because of significant heterogeneity in the classification of asymptomatic patients, large scale studies are required.

Takotsubo syndrome vs anterior STEMI electrocardiography; a meta-analysis and systematic review.

BACKGROUND: Takotsubo syndrome (TTS) and its differentiation from anterior wall ST-elevation myocardial infarction on electrocardiography (ECG) has been a debate. METHODS: Six studies comparing ECG changes in TTS and AW-STEMI were identified. The primary endpoint was reciprocal changes, presence of Q-waves, and QT-interval. An unadjusted odds ratio (OR) with a 95% confidence interval (CI) was calculated using Review Manager (RevMan) 5.3. RESULTS: Six studies consisting of 1090 patients (TTS = 220, AW-STEMI = 870) were included. Reciprocal changes on ECG were less commonly associated with TTS than AW STEMI with OR of 0.05 and 95%CI- 0.02-0.11 (P-<0.00001). Q-wave presence on ECG was comparable between the groups with OR-0.68, 95%CI-0.08-5.63 (p-0.72). QT interval on ECG was comparable between the two groups with OR-1.09, 95%CI-0.63-1.54 (p-<0.00001). There was minimal publication bias among the studies. CONCLUSION: AW STEMI is associated with reciprocal changes. Q-waves and QT interval has no differentiating significance between AW STEMI and TTS.

Comparing Transcatheter Aortic Valve Replacement (AVR) With Surgical AVR in Lower Risk Patients: A Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Transcutaneous aortic valve replacement (TAVR) is a novel percutaneous procedure for severe aortic stenosis and has been recently approved by Food and Drug Administration in lower risk patients. We performed the first ever meta-analysis and literature review of clinical trials comparing both 30-day and 1-year outcomes in lower risk patients undergoing TAVR vs. surgical aortic valve replacement (SAVR, having Society of Thoracic Surgeons score < 4% or equivalent). METHODS: Using predefined selection criteria as above, 68 articles were identified. Seven eligible articles were selected after extensive review. Primary effect outcomes were 30-day and 1-year all-cause mortality using risk ratio (RR) with significant P value of < 0.05. RESULTS: A total of 4,859 subjects were included. Risk of 30-day all-cause mortality was 40.1% less in TAVR group, RR 0.59 (95% confidence interval (CI): 0.38 - 0.92, P = 0.02) with no significant heterogeneity. Six studies except Schymik et al also reported 1-year risk. This was, however, not statistically significant with a 21% decrease in the TAVR group, RR 0.79 (95% CI: 0.57 - 1.09, P = 0.15). Six studies reported 30-day risk of secondary outcomes. The risk of 30-day stroke was 36% less in TAVR group, although this was not statistically significant, RR 0.64 (95% CI: 0.38 - 1.9, P = 0.10). The risk of acute kidney injury (AKI) stage 2 and above was 56% less in post-TAVR patients, RR 0.43 (95% CI: 0.35 - 0.54, P < 0.001) with no heterogeneity. For vascular complications, RR was high in TAVR group 4.62 (95% CI: 1.42-15.18, P = 0.01). Significant heterogeneity was demonstrated though (I2 = 81). The risks for permanent pacemaker (PPM) were also higher in the TAVR group, RR 3.30 (95% CI: 2.04 - 5.33, P < 0.001) and significant heterogeneity was observed. After removing Thyregod et al and Partner 3 trial from the analysis, heterogeneity was removed, but the RR was still high 3.21 (95% CI: 2.54 - 4.068, P < 0.001). Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. The 30-day risk for infective endocarditis was RR 0.67 (95% CI: 0.13 - 3.48, P = 0.63). The 1-year risk was similarly low but not significant, RR 0.73 (95% CI: 0.28 - 1.92, P = 0.53). CONCLUSIONS: Among low risk patients, TAVR was found to be superior in short-term all-cause mortality and 1-year stroke, a result that was statistically significant for TAVR and close to significance for stroke. TAVR patients were also less likely to have post-operative bleeding and AKI stage 2 and beyond. Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. However, the rates of PPM and vascular complications are higher in TAVR patients. The results of TAVR in low risk population are thus extremely encouraging. However, the issue of long-term valve durability in this group needs further studies. Also, caution needs to be exercised while extending the indications to extremely young patients due to lack of enough studies.

Prosthetic Valve Endocarditis in Patients Undergoing TAVR Compared to SAVR: A Systematic Review and Meta-Analysis.

BACKGROUND: The risk of prosthetic valve endocarditis (PVE) in patients who underwent transcatheter aortic valve replacement (TAVR) is presumed to be high. METHODS: Electronic databases were searched to identify articles comparing the rate of PVE in post-TAVR and post-surgical aortic valve replacement (SAVR) patients. Pooled adjusted odds ratio (OR) was computed using a random-effects model. RESULTS: A total of 19 studies consisting of 84,288 patients, were identified. There was no significant difference in the odds of PVE between patients undergoing TAVR and SAVR, at 30-day (OR 0.62, 95% confidence interval (CI) 0.20-1.92, p = 0.41), 1-year (OR 0.99 95% CI 0.89-1.11, p = 0.84), 2-year (OR 1.02 95% CI 0.68-1.54, p = 0.92) and 5-year (OR 1.03 95% CI 0.80-1.33, p = 0.81). A subgroup sensitivity analysis also showed no significant inter-group differences in the rate of PVE at all time points, when stratified by the study design (clinical trial vs. observational), type of TAVR valves used (self-expanding bioprosthetic valves vs. balloon expanded bioprosthetic valves) and surgical risk of patients (high vs. intermediate vs. low). There was no heterogeneity (I2 = 0%) in the outcomes of the included studies at 30-day, 1-year and 2-year, while the heterogeneity in studies at 5-year was minimal (I2 = 22%). CONCLUSIONS: In comparison to SAVR, both short and long-term risk of prosthetic valve endocarditis appears to be identical in patients undergoing TAVR. This risk is unaffected by the type of valve, duration of follow-up, study design and surgical risk of the patients.

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis.

Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. Results: The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month follow-up visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL (p = 0.037) and 6.2 mg/dL (p = 0.008), respectively, from baseline values. Conclusion: PCSK-9 inhibitors should be used cautiously with a follow-up liver function test.

Curcumin Preparations Can Improve Flow-Mediated Dilation and Endothelial Function: A Meta-Analysis.

INTRODUCTION: Endothelial dysfunction is an early marker of atherosclerosis. Flow-mediated dilation (FMD), measured by ultrasonography, is used to noninvasively assess endothelial dysfunction. Preparations of curcumin, a naturally occurring pigment found in turmeric, may improve FMD and thus endothelial dysfunction. We did a systematic review and meta-analysis to analyze the effect of curcumin preparations on endothelial dysfunction. METHODS: Five randomized clinical trials met the inclusion criteria for meta-analysis. The primary outcome was an improvement in FMD, as measured at brachial artery, after supplementations with curcumin preparations compared to the control group. Standardized mean difference and Hedges' g were used for effect size (ES) measurement. An ES of 0.2-0.5 is considered small, 0.5-0.8 is medium, and more than 0.8 is large. Publication bias was studied too. RESULTS: We found supplementation with curcumin preparations had an overall ES (standard difference in means) of 1.379 (95% CI 0.485-2.274, p = 0.003) on FMD. The overall Hedges' g was 1.353 (95% CI 0.47-2.235, p = 0.03). This analysis suggests a positive and large ES of curcumin preparations on FMD using a random effect model. Smokers had a smaller increase in FMD compared to nonsmokers (ES 0.379 vs. 1.639, p = 0.034). CONCLUSION: This meta-analysis of 5 randomized clinical trials indicates a significant effect of curcumin preparations to increase the FMD compared to placebo and thus endothelial function. This effect is not strongly noticed in smokers.

Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis.

OBJECTIVES: The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials. METHODS: A systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy. RESULTS: WB-MRI at 1.5T or 3.0T is feasible for image acquisition. Short tau inversion recovery (STIR) sequence is used in all investigations to date, suggesting consensus about the utility of this sequence for detection of WB tumor burden in people with NF. There are insufficient data to support a consensus statement about the optimal imaging planes (axial vs coronal) or 2D vs 3D approaches. Functional imaging, although used in some NF studies, has not been systematically applied or evaluated. There are no comparative studies between regional vs WB-MRI or evaluations of WB-MRI reproducibility. CONCLUSIONS: WB-MRI is feasible for identifying tumors using both 1.5T and 3.0T systems. The STIR sequence is a core sequence. Additional investigation is needed to define the optimal approach for volumetric analysis, the reproducibility of WB-MRI in NF, and the diagnostic performance of WB-MRI vs regional MRI.