Outcomes with treatment interventions for clot-in-transit in patients with pulmonary embolism: a meta-analysis.

OBJECTIVES: Clot-in-transit (CIT) in patients with pulmonary embolism (PE) has been associated with a high mortality rate and poor prognosis. The aim of this study was to evaluate the pooled efficacy of each of the 4 interventions (anticoagulation [AC] alone, systemic thrombolytic [ST] therapy, surgical thrombectomy, and catheter-based thrombectomy [CBT]) using mortality as the primary outcome. METHODS: A time limited search until March 28, 2024 was conducted using PubMed (National Institutes of Health) and EMBASE (Elsevier) databases. RESULTS: Thirteen studies (6 retrospective, 4 non-randomized prospective, and 3 pooled studies of case-reports) were included in the calculation of weighted proportion of mortality, including a total of 492 patients with CIT and PE with a mean age of 60.6 years; 50.1% were males. ST was the most frequently used treatment intervention (38.2%), followed by surgical thrombectomy (33.8%), AC alone (22.6%), and CBT (5.9%). The unweighted mortality was highest with AC alone 32.4% (36/111), followed by surgical thrombectomy 23.2% (38/164), CBT 20.7% (6/29), and ST 13.8% (26/188). The weighted mortality for AC alone was 35% (95% CI, 21% to 49%; 12 studies), surgical thrombectomy was 31% (95% CI, 16% to 47%; 12 studies), CBT was 20% (95% CI, 6% to 34%; 3 studies), and ST was 12% (95% CI, 5% to 19%; 12 studies). CONCLUSIONS: In this meta-analysis of patients with CIT and PE, the highest mortality was observed with AC alone, followed by surgical thrombectomy, CBT, and ST therapy. However, there remains a need for randomized clinical trial data to determine the best treatment.

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases: A Systematic Review and Meta-Analysis.

Importance: Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. Objective: To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. Data Sources: PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. Study Selection: This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. Data Extraction and Synthesis: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. Main Outcomes and Measures: Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. Results: The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). Conclusions and Relevance: In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Unfavorable social determinants of health and mortality risk by cardiovascular disease status: Findings from a National Study of United States Adults.

BACKGROUND: The association between cumulative burden of unfavorable social determinants of health (SDoH) and all-cause mortality has not been assessed by atherosclerotic cardiovascular disease (ASCVD) status on a population level in the United States. METHODS: We assessed the association between cumulative social disadvantage and all-cause mortality by ASCVD status in the National Health Interview Survey, linked to the National Death Index. RESULTS: In models adjusted for established clinical risk factors, individuals experiencing the highest level of social disadvantage (SDoH-Q4) had over 1.5 (aHR = 1.55; 95%CI = 1.22, 1.96) and 2-fold (aHR = 2.21; 95% CI = 1.91, 2.56) fold increased risk of mortality relative to those with the most favorable social profile (SDoH-Q1), respectively for adults with and without ASCVD; those experiencing co-occurring ASCVD and high social disadvantage had up to four-fold higher risk of mortality (aHR = 3.81; 95%CI = 3.36, 4.32). CONCLUSIONS: These findings emphasize the importance of a healthcare model that prioritizes efforts to identify and address key social and environmental barriers to health and wellbeing, particularly in individuals experiencing the double jeopardy of clinical and social risk.

Do We Still Need Aspirin in Coronary Artery Disease?

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization.

Treating Iron Deficiency (ID) Anemia in Heart Failure (HF) Patients with IV Iron: A Meta-Analysis.

Findings on the effects of iron on heart failure (HF) hospitalizations and mortality among patients with iron deficiency (ID) and HF remain conflicting across different studies. We performed a meta-analysis of clinical trials assessing the clinical, hematic and cardiovascular benefits of treating ID in HF patients. We completed a systematic search for studies comparing IV iron to placebo in HF patients with ID. The primary outcomes were rates of HF hospitalization and all-cause mortality. Secondary outcomes included change in hematic values, New York Heart Association (NYHA) class and ejection fraction. We applied a random-effects model with planned sensitivity analyses of studies with skewed effect sizes. Nine studies were included with a total of 2,261 patients. Analysis revealed that treatment of HF patients with IV iron replacement significantly reduced the odds of HF hospitalization (odds ratio (OR): 0.44; 95% confidence interval (CI): 0.24 to 0.78; p=0.005, I2=67%),) but did not significantly impact all-cause mortality compared to placebo (OR: 0.89; 95%, CI: 0.67 to 1.19; p=0.44, I2: 0%). Analysis showed that IV iron treatment group had significantly higher serum ferritin, transferrin saturation and hemoglobin (Hb) levels. They also had lower NYHA class -1.90 (95% CI (-2.91 to -0.89); p<0.001, I2:89%) with higher ejection fraction 0.50 (95% CI (0.09 to 0.90) p=0.016, I2:86%). Treatment with IV iron in HF patients with ID is associated with a significant reduction of HF hospitalization but no effects on all-cause mortality. There were also significant increases in hematic values and ejection fraction with a reduction in NYHA class.

An Individual Patient-Level Meta-Analysis of Ischemic Versus Nonischemic Cardiomyopathy and Trajectory of Decongestion in Patients With Acute Decompensated Heart Failure.

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.

Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening. METHODS: A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure (BP) parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes. RESULTS: Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory BP parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48-2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12-1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01-5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92-3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01-1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10-1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25 734 patients) were omitted (Pheterogeneity<0.05 for most outcomes), the above effect of evening dosing attenuated with no significant effect on 24/48-hour ambulatory blood pressure, day-time BP, and major adverse cardiac event and smaller reduction in night-time ambulatory SBP and DBP. CONCLUSIONS: Evening dosing of antihypertensive drugs significantly reduced ambulatory BP parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time BP, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects.

Optimal Hemostatic Band Duration After Transradial Angiography or Intervention: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials.

BACKGROUND: The optimal duration of hemostatic compression post transradial access is controversial. Longer duration increases the risk of radial artery occlusion (RAO) while shorter duration increases the risk of access site bleeding or hematoma. As such, a target of 2 hours is typically used. Whether a shorter or longer duration is better is not known. METHODS: A PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials of different duration (<90 minutes, 90 minutes, 2 hours, and 2-4 hours) of hemostasis banding. The efficacy outcome was RAO, primary safety outcome was access site hematoma, and secondary safety outcome was access site rebleeding. Primary analysis compared the effect of various duration in reference to the 2 hours duration using a mixed treatment comparison meta-analysis. RESULTS: Of the 10 randomized clinical trials included with 4911 patients, when compared to the 2-hour reference duration, there was a significantly higher risk of access site hematoma with 90 minutes (odds ratio, 2.39 [95% CI, 1.40-4.06]) and <90 minutes (odds ratio, 3.61 [95% CI, 1.79-7.29]) but not with the 2 to 4 hours duration. When compared with the 2-hour reference, there was no significant difference in access site rebleeding or RAO with shorter or longer duration but the point estimates favored longer duration for access site rebleeding and shorter duration for RAO. Duration of <90 minutes and 90 minutes ranked 1 and duration of 2 hours ranked 2 as the most efficacious duration whereas duration of 2 hours ranked 1 and 2 to 4 hours ranked 2 as the safest duration. CONCLUSIONS: In patients undergoing transradial access for coronary angiography or intervention, a hemostasis duration of 2 hours offers the best balance for efficacy (prevention of RAO) and safety (prevention of access site hematoma/rebleeding).

Trajectory of Decongestion and Mortality in Young Adults with Acute Heart Failure.

Although the prevalence of HF in young adults (age <50 years) is increasing, there are limited data on the trajectory of decongestion and short-term outcomes in young adults with acute heart failure (AHF). We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network (the Diuretic Optimization Strategies trial, the Renal Optimization Strategies Trial, and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The association between young age (<50 years and >50 years) and in-hospital changes in various measures of decongestion as well as short-term outcomes including risk for rehospitalization, and all-cause mortality was evaluated. Of 762 patients, 72 (10.3%) patients were young. Young adults were more likely to be African American (53.8% vs 19.3%), to have a lower rate of ischemic HF etiology (25.6% vs 60.4%, P <0.001), and a lower burden of hypertension, chronic kidney disease and atrial fibrillation. Young adults had a lower left ventricular ejection fraction (median 20% vs 33%, P < 0.001); they had a higher admission weight (median 242.7 lbs vs 201.5 lbs, P < 0.001), but lower NT-pro BNP levels (median 3622 pg/mL vs 4676 pg/mL, P = 0.003). After covariate adjustment, there was no difference in the change in NT-pro BNP (P = 0.25), net fluid loss (P = 0.42), or renal function (P = 0.56) between young and older adults by 72 or 96 hours of randomization. There was no difference in orthodema congestion score or the composite clinical endpoint during the follow-up (all-cause mortality or any rehospitalization) (adjusted odds ratios (95% confidence intervals): 2.51 (0.78-8.01), P = 0.12). In this pooled analysis of 3 clinical trial cohorts, compared with older adults, younger adults had a unique demographic and clinical profile. Despite these differences, there was no difference by age group in in-hospital decongestion or post-discharge readmission or mortality.

Sex differences in outcomes of transvenous lead extraction: insights from National Readmission Database.

BACKGROUND: With the growing use of implantable cardiac devices, the need for transvenous lead extraction has increased, which translates to increased procedural volumes. Sex differences in lead extraction outcomes are not well studied. OBJECTIVE: The present study aims at evaluating the impact of sex on outcomes of lead extraction. METHODS: We identified 71,754 patients who presented between 2016 and 2019 and underwent transvenous lead extraction. Their clinical data were retrospectively accrued from the National Readmission Database (NRD) using the corresponding diagnosis codes. We compared clinical outcomes between male and female patients. Odds ratios (ORs) for the primary and secondary outcomes were calculated, and multivariable regression analysis was utilized to adjust for confounding variables. RESULTS: Compared to male patients, female patients had higher in-hospital complications including pneumothorax (OR 1.26, 95% CI (1.07-1.4), P < 0.01), hemopericardium (OR 1.39, 95% CI (1.02-1.88), P = 0.036), injury to superior vena cava and innominate vein requiring repair (OR 1.88, 95% CI (1.14-3.1), P = 0.014; OR 3.4, 95% CI (1.8-6.5), P < 0.01), need for blood transfusion (OR 1.28, 95% CI (1.18-1.38), P < 0.01), and pericardiocentesis (OR 1.6, 95% CI (1.3-2), P < 0.01). Thirty-day readmission was also significantly higher in female patients (OR 1.09, 95% CI (1.02-1.17), P < 0.01). There was no significant difference regarding in-hospital mortality (OR 0.99, 95% CI (0.87-1.14), P = 0.95). CONCLUSION: In female patients, lead extraction is associated with worse clinical outcomes and higher 30-day readmission rate.

Role of adjunct anticoagulant or thrombolytic therapy in cardiac arrest without ST-segment-elevation or percutaneous coronary intervention: A systematic review and meta-analysis.

This study sought to compare the impact of additional anticoagulation or thrombolytic therapy in patients with cardiac arrest without ST-segment-elevation on electrocardiography and not receiving percutaneous coronary intervention. Three studies (two randomized controlled studies and one observational study) were included, which demonstrated that use of anticoagulation or thrombolytic therapy was associated with higher risk of bleeding, without improvements in time to return of spontaneous circulation or in-hospital mortality.

Meta-Analysis on Invasive Versus Conservative Strategy in Patients Older Than Seventy Years With Non-ST Elevation Myocardial Infarction.

Management of non-ST elevation myocardial infarction (NSTEMI) has evolved over the years, but most published data are from younger patients. Data on the NSTEMI management in older patients remain limited. We performed a meta-analysis of randomized controlled trials to evaluate the long-term outcomes of invasive versus conservative strategies in older patients (>70 years old) with NSTEMI. Of 1,550 reports searched, 4 randomized controlled trials (1,126 patients) were included in the analysis, with a median follow-up of 1.25 years (range: 1 to 2.5 years). The median age of included patients was 83.6 (interquartile range: 2.8 years). The invasive strategy was associated with significantly lower risk of major adverse cardiac and cerebrovascular event (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.40 to 0.91, I2 = 54%; 3 trials] and unplanned revascularization (OR 0.31, 95% CI 0.15 to 0.64, I2 = 1.7%; 3 trials] than was the conservative strategy. There was no difference in all-cause mortality (OR 0.88, 95% CI 0.65 to 1.18, I2 = 0%; 4 trials], myocardial infarction (OR 0.70, 95% CI 0.42 to 1.19, I2 = 54.7%; 4 trials], or bleeding (OR 0.87, 95% CI 0.39 to 1.93, I2 = 0%; 3 trials] between the strategies. In conclusion, the use of initial invasive strategy in older patients presenting with NSTEMI was associated with a significantly lower risk of major adverse cardiac and cerebrovascular event and unplanned revascularization than that of the initial conservative strategy without increased bleeding.

Cumulative Social Disadvantage and All-Cause Mortality in the United States: Findings from a National Study.

The extent to which cumulative social disadvantage-defined as aggregate social risk resulting from multiple co-occurring adverse social determinants of health (SDOH)-affects the risk of all-cause mortality, independent of demographic and clinical risk factors, is not well understood. The objective of this study was to examine the association between cumulative social disadvantage, measured using a comprehensive 47-factor SDOH framework, and mortality in a nationally representative sample of adults in the United States. The authors conducted secondary analysis of pooled data for 63,540 adult participants of the 2013-2015 National Death Index-linked National Health Interview Survey. Age-adjusted mortality rates (AAMRs) were reported by quintiles of aggregate SDOH burden, with higher quintiles denoting greater social disadvantage. Cox proportional hazards models were used to examine the association between cumulative social disadvantage and risk of all-cause mortality. AAMR increased significantly with greater SDOH burden, ranging from 631 per 100,000 person-years (PYs) for participants in SDOH-Q1 to 1490 per 100,000 PYs for those in SDOH-Q5. In regression models adjusted for demographics, being in SDOH-Q5 was associated with 2.5-fold higher risk of mortality, relative to Q1 (adjusted hazard ratio [aHR] = 2.57 [95% confidence interval, CI = 1.94-3.41]); the observed association persisted after adjusting for comorbidities, with over 2-fold increased risk of mortality for SDOH-Q5 versus Q1 (aHR = 2.02 [95% CI = 1.52-2.67]). These findings indicate that cumulative social disadvantage is associated with increased risk of all-cause mortality, independent of demographic and clinical factors. Population level interventions focused on improving individuals' social, economic, and environmental conditions may help reduce the burden of mortality and mitigate persistent disparities.

Impact of concomitant aortic stenosis on the management and outcomes of acute myocardial infarction hospitalizations in the United States.

Objective: To evaluate the prevalence, management and outcomes of concomitant aortic stenosis (AS) in admissions with acute myocardial infarction (AMI). Methods: We used the HCUP-NIS database (2000-2017) to identify adult AMI admissions with concomitant AS. Outcomes of interest included prevalence of AS, in-hospital mortality, use of cardiac procedures, hospitalization costs, length of stay, and discharge disposition. Results: Among a total of 11,622,528 AMI admissions, 513,688 (4.4 %) were identified with concomitant AS. Adjusted temporal trends revealed an increase in STEMI and NSTEMI hospitalizations with concomitant AS. Compared to admissions without AS, those with AS were on average older, of female sex, had higher comorbidity, higher rates of NSTEMI (78.9 % vs 62.1 %), acute non-cardiac organ failure, and cardiogenic shock. Concomitant AS was associated with significantly lower use of coronary angiography (45.5 % vs 64.4 %), percutaneous coronary intervention (20.1 % vs 42.5 %), coronary atherectomy (1.7 % vs. 2.8 %) and mechanical circulatory support (3.5 % vs 4.8 %) (all p < 0.001). Admissions with AS had higher rates of coronary artery bypass surgery and surgical aortic valve replacement (5.9 % vs 0.1 %) compared to those without AS. Admissions with AMI and AS had higher in-hospital mortality (9.2 % vs. 6.0 %; adjusted OR 1.12 [95 % CI 1.10-1.13]; p <0.001). Concomitant AS was associated with longer hospital stay, more frequent palliative care consultations and less frequent discharges to home. Conclusions: In this 18-year study, an increase in prevalence of AS in AMI hospitalization was noted. Concomitant AS was associated with lower use of guideline-directed therapies and worse clinical outcomes among AMI admissions.

Impact of Chronic Obstructive Pulmonary Disease on Atrial Fibrillation Ablation Outcomes According to the National Readmission Database.

Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of atrial fibrillation (AF). There is a paucity of contemporary data studying the association between COPD and outcomes of AF ablation. The objective of this study was to investigate the impact of COPD on AF ablation outcomes using a large nationwide database. This study was a retrospective analysis of the National Readmission Database for the years 2016-2018 and included patients admitted with a diagnosis of AF who underwent catheter ablation. Admissions were stratified according to COPD diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariate, linear, Cox, and logistic regressions were performed to study the impact of COPD on AF ablation. A total of 18,224 admissions (mean age, 68 years; standard deviation, 10 years) were included, of whom 3,494 (19%) had a diagnosis of COPD. The COPD group was older (72 ± 8 vs. 67 ± 11 years, P < .001) and more likely to have congestive heart failure (73% vs. 44%, P < .001) and renal failure (31% vs. 17%, P < .001). COPD was associated with an increased risk of readmission (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [CI], 1.26-1.56; P < .001) and all-cause in-hospital mortality (adjusted odds ratio, 2.83; 95% CI, 1.74-4.60; P < .001). However, COPD was not associated with an increased risk of readmission due to recurrent AF (aHR, 0.97; 95% CI, 0.75-1.27; P = .844) or the need for re-ablation (aHR, 0.85; 95% CI, 0.44-1.65; P = .639), respectively. In conclusion, COPD was not associated with an increased risk of recurrent AF after ablation despite higher periprocedural risks. The present study contributes to a better understanding of this high-risk subgroup of patients undergoing AF ablation.

Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: Janus kinase (JAK) inhibition effectively treats immune-mediated inflammatory diseases (IMIDs); however, concern over the risk of major adverse cardiac events (MACE) and venous thromboembolism (VTE) remains. We aimed to evaluate the safety (VTE and MACE outcomes) of JAK inhibitors in the treatment of IMIDs. METHODS: A search in PubMed, Embase, and ClinicalTrials.gov databases was conducted for randomized clinical trials (RCTs) of JAK inhibitors across IMIDs. Primary outcomes were VTE and MACE with JAK inhibitors compared with placebo and active comparator arms stratified by follow-up time. RESULTS: Sixty-six RCTs enrolled 38,574 patients with a mean age of 48.8 years and a mean follow-up of 10.5 months. JAK inhibitors had a numerically higher rate of VTE when compared with controls (odds ratio [OR] 1.65; 95% confidence interval [CI]: 0.97-2.79), driven by trials with a follow-up duration of 12 or more months (OR 2.17; 95% CI: 1.16-4.05; Pinteraction = 0.05). When compared with active comparators, JAK inhibitors increased VTE in clinical trials with 12 or more months' versus less than 12 months' follow-up time (OR 2.38 [95% CI: 1.24-4.57] vs 0.30 [95% CI: 0.07-1.26], respectively; Pinteraction = 0.01). No increased risk of VTE was seen when comparing JAK inhibitors with placebo arms. For the outcome of MACE, the results were largely similar but did not reach statistical significance (OR 1.19; 95% CI: 0.86-1.64). CONCLUSION: JAK inhibitors when compared with active comparator arms increased the risk of VTE, which was dependent on duration of exposure. Future clinical trials with extended follow-up are needed to clarify the safety profiles of JAK inhibitors.

Non-Alcoholic Fatty Liver Disease, Heart Failure, and Long-Term Mortality: Insights From the National Health and Nutrition Examination Survey.

To evaluate the association between non-alcoholic fatty liver disease (NAFLD), heart failure (HF), and all-cause mortality. Both NAFLD and HF are increasing in prevalence due to shared risk factors. We used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 to identify non-pregnant individuals aged ≥20 years with HF and NAFLD and linked with the cause of death data from the National Center for Health Statistics. The associations between NAFLD, HF, and all-cause mortality were assessed using logistic regression and Cox proportional hazard modeling as appropriate. There were 82,358,893 weighted eligible participants of whom 3,833,667 (4.7%) had NAFLD. The mean (SE) age was 51.5 (0.35) years, 45.1% women, 63.0% Non-Hispanic White and 11.8% Non-Hispanic Black. Cardiovascular comorbidities were more common in participants with NAFLD; they were more likely to have hypertension (81.7% vs 53.5%), diabetes (65.1% vs 17.1%), stroke (7.3% vs 4.1%), coronary artery disease (14.9% vs 8.4%), or HF (10.5% v s 3.5%) compared with participants without NAFLD. In multivariate logistic regression models adjusting for age, race/ethnicity and sex, participants with NAFLD were 3.5 times more likely to have HF [aOR, 95% CI: 3.47 (1.98-6.06)]. Older age, male sex, presence of diabetes and coronary artery disease were associated with higher odds of HF in participants with established NAFLD. At the end of the follow-up period, participants with NAFLD had higher all-cause mortality compared with participants without NAFLD (HR [95% CI]: 1.93 [1.24-2.99], P < 0.001). In this analysis of US adults, ambulatory participants with NAFLD were ∼3.5 times more likely to have HF, and twice as likely to experience mortality compared with participants without NAFLD. Further studies are needed to identify the possible linkage between NAFLD and HF beyond the shared risk factor pathogenesis.