Efficacy Outcomes Research Articles

Risk-stratified treatment for drug-susceptible pulmonary tuberculosis

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54–0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07–1.91; extensive disease: HR 2.02, 95%CI 1.07–3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

Reporting outcomes of minimally invasive glaucoma surgery.

This review presents guidelines for designing studies and reporting efficacy and safety outcomes in minimally invasive glaucoma surgery (MIGS) research. Adherence to reporting guidelines in MIGS studies is crucial for providers and patients to appraise surgical options. Recent guidelines have outlined appropriate methodology, efficacy outcomes, and safety reporting, so that study results are presented in an interpretable and uniform manner. MIGS are changing the glaucoma treatment paradigm by offering safer, less invasive alternatives to traditional filtering surgery. However, inconsistent reporting of outcomes in MIGS trials hampers comparison and clinical decision-making. Recent guidelines have aimed to highlight appropriate methodology and encourage standardization in reporting outcomes to improve the quality of MIGS literature. Key considerations include defining baseline intraocular pressure, reporting standardized demographic data, using consistent endpoints, presenting standardized figures, evaluating medication use, and documenting adverse events. By adhering to these guidelines, MIGS trials can offer clearer insights into surgical outcomes, aiding both surgeons and patients in treatment decisions.

Risk-Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis.

This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG). Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a≥3- or≥5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA. Efgartigimod IV had the lowest NNT versus placebo for achieving a≥3- and≥5-point reduction in QMG, as well as a≥5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a≥3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors. FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+gMG.

Clinical Investigation of Short-Term Axial Elongation Control After Orthokeratology Lens Correction: Exploring Its Predictive Role in Long-Term Therapeutic Efficacy

Objective: This study was developed with the goal of exploring the efficacy of orthokeratology (OK) as an approach to controlling axial length (AL) growth and identifying factors predictive of the long-term efficacy of this approach. Methods: This was a retrospective study that enrolled 157 myopic children 7 to 15 years of age undergoing OK correction for over 3 years. The short- and long-term effectiveness of this approach at 1 and 3 years post-OK correction, respectively, was assessed. All participants were classified into two groups based on whether they exhibited good or poor long-term efficacy outcomes. Measurements of changes in AL were made at baseline and at 1 and 3 years post-OK. Univariate analyses and binary logistic regression approaches were used to evaluate baseline age, baseline spherical equivalent refraction, baseline keratometry (K) values of flat and steep meridians, and short-term effectiveness with the goal of identifying predictors of long-term efficacy. Results: Univariate analyses led to the identification of significant differences in baseline age, baseline spherical equivalent refraction, baseline AL, and short-term efficacy between these two groups (P<0.05), whereas gender, baseline flat K, and baseline steep K did not differ significantly (P>0.05). In binary logistic regression analyses, baseline AL (P=0.017) and short-term efficacy (P<0.001) were both found to significantly influence long-term efficacy. Receiver operating characteristic curves demonstrated that short-term efficacy offered an area under the curve value >0.8, consistent with its highly accurate performance as a predictor of long-term efficacy. Conclusion: These results suggest that short-term efficacy outcomes can feasibly be used to predict the long-term effectiveness of OK correction in children. In patients exhibiting poor short-term efficacy, timely replacement or the incorporation of additional treatment modalities may aid efforts to better control the progression of myopia.

12-month Safety and Efficacy Outcomes of a Standalone Trabecular Bypass Device

12-month Safety and Efficacy Outcomes of a Standalone Trabecular Bypass Device

Platinum Resistance in Ovarian Cancer: Is This the End of the Line?

Approximately 80% of females with ovarian cancer are diagnosed with advanced disease, and around 70% of these females relapse within 3 years of first-line treatment. Five-year survival for newly diagnosed advanced ovarian cancer is less than 50%. Platinum-based chemotherapy is the cornerstone of systemic treatment; however, it is not appropriate for patients with relapsed ovarian cancer who had disease progression during previous platinum treatment, early symptomatic progression post-platinum treatment, or who are platinum intolerant. New drugs are needed to address the unmet need in patients with relapsed ovarian cancer who are not eligible for platinum-based chemotherapy. This article presents highlights from a satellite symposium conducted as part of the European Society for Medical Oncology (ESMO) Congress 2024, which took place from 13th–17th September 2024 in Barcelona, Spain. The objectives of the symposium were to improve understanding of the current treatment pathways and unmet needs for patients with ovarian cancer who are ineligible for platinum-based therapies, to raise awareness of the rationale for targeting folate receptor α (FRα) in a variety of novel therapeutics for platinum-resistant ovarian cancer (PROC), and to review the efficacy outcomes and side effects from recent clinical trials involving antibody–drug conjugates (ADC) in PROC. In this symposium, Ana Oaknin, Vall d’Hebron University Hospital, Barcelona, Spain, described the current landscape in advanced ovarian cancer and the unmet need in relapsed disease; Philipp Harter, Evangelische Kliniken Essen-Mitte, Germany, explored FRα-targeted therapeutics in PROC; and Kathleen Moore, Stephenson Cancer Center, University of Oklahoma, Norman, USA, discussed ADC development beyond FRα in PROC. The symposium concluded with a lively discussion, including questions from the audience, key examples of which are included in this article.

Optimal anticoagulant strategy for periprocedural management of atrial fibrillation ablation: a systematic review and network meta-analysis

Abstract Background This network meta-analysis was performed to rank the safety and efficacy of periprocedural anticoagulant strategies in patients undergoing atrial fibrillation ablation. Methods MEDLINE, EMBASE, CENTRAL, and Web of Science were searched to identify randomized controlled trials comparing anticoagulant regimens in patients undergoing atrial fibrillation ablation up to July 1, 2021. The primary efficacy and safety outcomes were thromboembolic and major bleeding events, respectively, and the net clinical benefit was investigated as the primary-outcome composite. Results Seventeen studies were included (n = 6950). The mean age ranged from 59 to 70 years; 74% of patients were men and 55% had paroxysmal atrial fibrillation. Compared with the uninterrupted vitamin-K antagonist strategy, the odds ratios for the composite of primary safety and efficacy outcomes were 0.61 (95%CI: 0.31–1.17) with uninterrupted direct oral anticoagulants, 0.63 (95%CI: 0.26–1.54) with interrupted direct oral anticoagulants, and 8.02 (95%CI: 2.35–27.45) with interrupted vitamin-K antagonists. Uninterrupted dabigatran significantly reduced the risk of the composite of primary safety and efficacy outcomes (odds ratio, 0.21; 95%CI, 0.08–0.55). Conclusion Uninterrupted direct oral anticoagulants are preferred alternatives to uninterrupted vitamin-K antagonists. Interrupted direct oral anticoagulants may be feasible as alternatives. Our results support the use of uninterrupted direct oral anticoagulants as the optimal periprocedural anticoagulant strategy for patients undergoing atrial fibrillation ablation.

Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2

Comparative analysis of vitamin K antagonists and direct oral anticoagulants for left ventricular thrombus management: a retrospective study utilising TriNetX

Abstract Introduction Despite progress in cardiovascular medicine, guidelines for addressing left ventricular thrombus (LVT) remain limited. Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction (MI) adds complexity to treatment decisions. While conventional guidance favors vitamin K antagonists (VKAs), emerging evidence suggests favorable outcomes with direct oral anticoagulants (DOACs). Purpose This study aims to assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). Methods This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity matching (PSM) for age, gender, ethnicities, medical and drug history. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. Results Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group and 24,162 in the non-ACS group. DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p<0.05) compared to VKA in the overall cohort (Table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p<0.05) but not bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p<0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in overall all causes of mortalities. Conclusion DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. Interestingly, DOACs utilisation within the ACS context resulted in a diminished risk of embolic complications without the benefit of reduced bleeding risk seen in patients without ACS, suggesting potential implications of triple therapy within first month of ACS treatment, removing the bleeding risk reduction of DOACs. This shows a fundamental difference in LVT between the 2 groups of patients so future studies should aim to differentiate between the 2.

Posterior wall isolation for persistent atrial fibrillation catheter ablation: an updated systematic review and meta-analysis

Abstract Background The ability of catheter ablation (CA) to prevent arrhythmic recurrences in patients with persistent atrial fibrillation (PeAF) remains suboptimal. In this context, the results of studies conducted with both thermal and non-thermal technologies, that evaluated the effect of adding electrical isolation of the posterior wall of the left atrium (PWI) to isolation of the pulmonary veins alone (PVI) have provided conflicting data. Purpose To compare the efficacy and safety of an ablative strategy with the addition of PWI to PVI versus PVI alone in patients with PeAF undergoing a first ablation procedure. Methods We searched electronic databases for observational studies and randomized controlled trials (RCTs) comparing PVI+PWI versus PVI alone as first CA procedure for PeAF, regardless of the technologies used. The efficacy outcomes were recurrence of any atrial tachyarrhythmias lasting more than 30 seconds, recurrence of atrial fibrillation (AF) and atrial flutter/atrial tachycardia (AFlu/AT). The safety outcome was relevant procedural complications defined as a composite of vascular complications, pericardial effusion or tamponade, phrenic nerve palsy, stroke, atrio-esophageal fistula, and death. The procedural time was compared between the ablation strategies studied. The software RevMan 5.4 was used to estimate the risk ratio (RR) and mean difference (MD) with the relative confidence intervals (CI), using a random-effect model. Results Thirteen studies (8 RCTs and 5 observational studies) counting a total of 2994 PeAF patients (1304 treated with PVI+PWI and 1690 with PVI alone; 1847 RF, 600 cryo and 547 PFA) were included in the analysis. Mean age was 65.2±4.1 years, and 26% were female. Mean follow-up period was 14.5±4.8 years. There were no significant differences in the risk of recurrence of any atrial tachyarrhythmias (RR 0.88; 95% CI 0.68-1.14) between the ablation strategies studied. Patients treated with PWI+PVI experienced a reduced risk of recurrence of AF (RR 0.67; 95% CI 0.48-0.94; p = 0.02) balanced by a trend towards increased risk of AFlu/AT (RR 1.74; 95% CI 0.99-3.06; p = 0.06) as compared with PVI alone strategy. No statistically significant differences in the risk of relevant procedural complication were identified between the studied groups (RR 0.94; 95% CI 0.50-1.78 – Fig. 2A). Procedural time was longer in the PWI+PVI group as compared with PVI alone (MD 30.63 min; 95% CI 8.60-52.65 min; p=0.006 – Fig. 2B). Conclusions Our metanalysis shows that, in patients with PeAF treated for the first time with CA, PWI+PVI versus PVI alone was not associated with a reduction of atrial tachyarrhythmias recurrence and required longer procedural times. Nonetheless, a reduction in the risk of AF recurrence and a trend towards an increased risk of AFlu/AT were identified. No differences in the risk of relevant procedural complications were found between the ablation strategies studied.Figure 2

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (<25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value <0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI <25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI <25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI <25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Heparin reversal for coronary artery perforation

Abstract Background/Introduction In the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI), heparin reversal can provide hemostatic effects but raises concerns about potential coronary thrombosis if an intracoronary artery guidewire or balloon is in place. Purpose We aimed to evaluate the safety and efficacy of heparin reversal during device insertion for CAP. We also aimed to determine the optimal target activated clotting time (ACT) to maintain when performing heparin reversal. Methods We analyzed cases of CAP which occurred during PCI procedures in a single center from January 2006 to October 2023. Patients were assigned to two groups according to whether they received heparin reversal with a device in place. The safety outcome was the periprocedural myocardial infarction (creatine kinase-MB >5 times the upper normal limit), and the efficacy outcome was successful hemostasis at the end of the procedures (complete absence of CAP on angiography). Results Among the 22,368 cases, 368 (1.6%) developed CAP, consisting of main vessels 45%, distal vessels 43%, and collateral vessels 12%. Heparin reversal with a device in place was implemented in 211 (57%) cases. Of these, 16 (7.6%) experienced coronary thrombosis. After adjusting covariates by the multivariable logistic regression model, heparin reversal with a device in place was significantly associated with a higher incidence of periprocedural myocardial infarction (11% vs 4.5%; adjusted OR: 3.11; 95% CI: 1.24–7.78; P = 0.015) and a higher rate of successful hemostasis (91% vs 73%; adjusted OR: 2.78; 95% CI: 1.27–6.09; P = 0.011). In the analysis of cases where minimum ACT value was available (n = 251), this value was significantly correlated with coronary thrombosis (r = −0.16, P = 0.012). When the cutoff values of minimum ACT were set at 200, 150, and 120 seconds as a binomial variable, the correlation coefficient was r = −0.08 (P = 0.158), r = −0.16 (P = 0.009), r = −0.20 (P = 0.001), respectively. Conclusions Heparin reversal after CAP with an intracoronary artery device in place was significantly associated with a higher incidence of periprocedural MI but also a higher rate of successful hemostasis. A minimum ACT value <150 seconds was significantly correlated with coronary thrombosis. These results propose a novel algorithm for CAP management strategies.Management algorithm for CAP

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.

Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment. This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction. In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity). A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity. This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.

Direct oral anticoagulants exhibit lower risks of mortality and bleeding compared to vitamin-k antagonists in atrial fibrillation patients on chronic hemodialysis: a meta-analysis

Abstract Background Atrial fibrillation (AF) is a common arrhythmia in patients with chronic kidney disease (CKD). Although direct oral anticoagulants (DOACs) are equally or more effective than vitamin K antagonists (VKAs) in patients with moderate CKD, evidence claiming the benefits of DOACs over VKAs in patients on hemodialysis (HD) is scarce. Purpose This meta-analysis aimed to assess the outcomes of patients with AF on chronic HD by comparing the clinical outcomes of DOACs versus VKAs. Methods A systematic literature search was conducted across various databases to retrieve studies focusing on efficacy and safety outcomes in patients with AF on chronic hemodialysis comparing DOACs and VKAs. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel random-effects model in Review Manager 5.4. Statistical significance was set at p <0.05. Results Nine studies with 39, 831 patients were included. The risk of all-cause mortality [RR: 0.73; 95% CI: 0.60, 0.88; p=0.001], major bleeding [RR: 0.63; 95% CI: 0.52, 0.76; p<0.00001], gastrointestinal bleeding [RR: 0.67; 95% CI: 0.53, 0.85; p=0.0009], intracranial hemorrhage [RR: 0.57; 95% CI: 0.38, 0.84; p=0.004], all-cause stroke [RR: 0.64; 95% CI: 0.51, 0.81; p=0.0001], and ischemic stroke [RR: 0.53; 95% CI: 0.29, 0.96; p=0.04] were lower in the DOAC group than in the VKA group. The risk of cardiovascular-related death [RR: 1.34; 95% CI: 0.69, 2.60; p=0.39], and clinically relevant non-major bleeding [RR: 0.90; 95% CI: 0.75, 1.08; p=0.26] showed no significant differences. Conclusion The risks of all-cause stroke, ischemic stroke, all-cause mortality, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage in the patients with AF undergoing chronic HD were lower in the DOAC group than in the VKA group. Further large-scale RCTs are needed to generate more robust evidence through adequately powered studies, leading to conclusive results that are applicable to real-world scenarios.

The impact of exercise training in Fontan procedure patients: a systematic review and meta-analysis

Abstract Background Patients undergoing the Fontan procedure experience long-term complications related to decreased exercise capacity. Exercise training(ET) has emerged as a non-pharmacological solution for increasing cardiorespiratory fitness. However, the effect and safety of exercise training in patients following the Fontan procedure are still unclear. Objectives We aimed to perform a meta-analysis comparing ET versus no exercise intervention for patients following Fontan operation in efficacy and safety outcomes. Methods We systematically searched PubMed, Embase, and Cochrane databases on November 23, 2023, for randomized controlled trials (RCTs) comparing ET, including aerobic, endurance, or inspiratory muscle training, versus no exercise intervention in patients following Fontan operation. We computed mean differences (MD) with a 95% confidence interval (CI) for continuous endpoints. The primary endpoint was (1) peak O2 consumption. Our study also included the secondary endpoints of: (2) maximum workload; (3) peak heart rate(HR); and (4) peak saturation of O2. We performed a subgroup analysis between different exercise therapies. Results This meta-analysis included five RCTs and 154 patients. Follow-up ranged from 3 to 6 months. Regarding ET, two studies used aerobics, one used endurance, and three used inspiratory muscle therapy as exercise therapy for patients with Fontan operations. Our findings on the maximum workload endpoint were more significant for exercise therapy (MD 20.98W; 95% CI 5.32 to 36.65; p<0.01; Fig. 1A) compared to no intervention group. However, there was no significant difference in peak oxygen (MD 2.03 ml/kg/min; 95% CI -0.29 to 4.35; p=0.095; Fig. 1B), peak HR (MD 1.10 bpm; 95% CI -4.07 to 6.27; p=0.68); and peak saturation of O2 (MD 0.39%; 95% CI -1.93 to 2.72; p=0.74). A subgroup analysis between different ET types (aerobic vs. endurance vs. inspiratory muscle training) showed no significant subgroup interaction(p=0.91; Fig. 1B). Conclusion In this meta-analysis, ET is associated with a slight increase in maximum workload in patients following the Fontan procedure. Further multicenter RCTs are warranted to assess the efficacy of comparing different types of ET and their impact on peak oxygen consumption.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p <0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable

Torsemide versus furosemide in patients with heart failure: a systematic review and meta-analysis

Abstract Introduction Loop diuretics are essential agents in the management of fluid overload conditions, heart failure and renal dysfunction. Despite their widespread use, there is ongoing debate regarding the relative efficacy, safety, and clinical outcomes associated with furosemide and torsemide. By systematically analyzing existing literature, this study seeks to provide a comprehensive evaluation of the comparative effectiveness and safety profiles of these two medications , Helping to inform clinical decision-making and contribute to the optimization of diuretic therapy in patients with heart and kidney diseases. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies comparing the torsemide and furosemide in Heart failure patients. Outcomes of interest were all-cause mortality, cardiovascular mortality, all-cause hospitalization, hospitalization for HF, and improvement of ≥ 1 in NYHA functional class. Results 16 studies were included in this meta-analysis with a total of 12545 patients, There were no significant results between the two drugs in all-cause mortality, cardiovascular mortality or all-cause hospitalization, torsemide showed a reduction in hospitalization from heart failure (RR 0.85, 95% CI [0.71 to 1.02]), torsemide showed a significant improvement of ≥ 1 in NYHA functional class (OR 1.60, 95% CI [1.18, 2.17]). Conclusion There was no difference between torsemide and furosemide when it comes to all-cause and cardiovascular mortality, but torsemide showed better results in reducing hospitalization rates and and improving quality of life.Hospitalization from heart failureImprovement ≥ 1 in NYHA class

Long-term efficacy and safety of ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) but data on safety and long-term outcomes after catheter ablation for AF in HCM are scarce. Purpose To investigate safety, long-term efficacy and clinical outcomes following AF ablation in patients with HCM and in matched controls. Methods Patients with HCM (n=76) undergoing a first catheter ablation for AF or atrial flutter between 1999 and 2022 at a University Hospital in Sweden were included (age 64±12 years, 43% female). Diagnosis of HCM was based on the European Society of Cardiology definition (left ventricular wall thickness ≥15 mm or ≥13 mm not solely explained by abnormal loading conditions, and combined with family history, genetic components and/or electrocardiogram abnormalities). Patients with HCM were matched with controls (n=152) based on age, gender, ablation type and intervention-year. Patients were followed for a mean of 5 years and study endpoints included heart failure hospitalization (HFH), stroke and mortality. Cox regression analyses were performed for the association between HCM and the endpoints. Results Among the overall population, 121 (53%) underwent pulmonary vein isolation (PVI), 62 (27%) isthmus ablation and 45 (20%) His-Bundle ablation. Patients with HCM had a shorter mean duration of AF before ablation (48 months vs. 66 months; p=0.047) and more severe symptoms as indicated by a higher EHRA class (EHRA class IV: 30% vs. 10%; p<0.01). Procedural success rate of PVI and isthmus ablation was lower in patients with versus without HCM (88% vs. 97%; p=0.02). Procedure related complications (vascular complications, tamponade) were overall similar in both groups (9% in HCM vs. 5% in controls, p=0.17) except for higher rates of pulmonary oedema in patients with HCM (7% vs 1%, p=0.03). There was a nearly two-fold increase in risk of AF recurrence after PVI or isthmus ablation in patients with HCM compared to controls (OR 1.95; 95% CI 1.06-3.58; p=0.03). During follow-up, patients with HCM had an increased risk of HFH (HR 2.55, 95% CI 1.21-5.36, p=0.01) but not of stroke or mortality (Figure 1). Conclusion AF ablation was overall safe in patients with HCM but less effective. Patients with HCM had an increased risk of the individual endpoint of HFH after AF ablation but not stroke or mortality during long-term follow-up.

Decision-analytic modelling of costs & benefits of adding sigmoidoscopy to CRC screening in Germany

Abstract Background In Germany, a colorectal cancer (CRC) screening programme is in place that entitles individuals to a stool test or colonoscopy. However, less than half of those eligible participate. The inclusion of an additional screening option, such as the evidence-based sigmoidoscopy, could lead to a higher overall participation rate, but also to individuals preferring the additional option to the more effective colonoscopy. The objective of this modelling study is to estimate the impact of offering sigmoidoscopy as an additional option for CRC screening in Germany. Methods A life-time mathematical model (Markov model) is developed to analyse the long-term effects of the additional offer of sigmoidoscopy on benefits (prevalence, mortality, health-related quality of life (HRQoL)), costs, and cost-effectiveness. The model is based on systematic literature reviews and real-world healthcare data. It incorporates disease development, sensitivity and specificity of the options, compliance rates, survival probabilities and background mortality. A discrete choice experiment (DCE) was conducted to estimate the future uptake of the options (stool test, colonoscopy, sigmoidoscopy, no screening) based on stated preferences of n = 666 individuals. Results Adding sigmoidoscopy leads to greater effectiveness of the CRC screening programme in terms of increased screening participation, increased adenoma detection, decreased disease-specific mortality, and improved discounted HRQoL. However, it also incurs higher costs. The incremental cost-effectiveness ratios (ICER) for men and women are €507 per quality-adjusted life year gained (QALYg) and €74 per QALYg, respectively. Conclusions The results indicate that the inclusion of sigmoidoscopy in the German CRC screening programme would be cost-effective and that sigmoidoscopy should be piloted in practice. The expanded programme has the potential to enhance the program’s effectiveness, improve health outcomes, and reduce the burden of CRC. Key messages • Expanding the CRC screening programme may increase overall participation, resulting in higher costs, but also greater effectiveness in detecting more adenomas, reducing mortality, improving HRQoL. • Introducing sigmoidoscopy in Germany appears cost-effective and justifies practical piloting to enhance CRC screening efficacy and health outcomes.

Right ventricular-pulmonary artery coupling and clinical outcomes after mitral transcatheter edge-to-edge repair: A meta-analysis

Abstract Introduction Mitral transcatheter edge-to-edge repair (TEER) has gained prominence in the realm of cardiovascular care, as it has been proven to improve patient prognosis and quality of life. While the primary focus of such interventions is the mitral valve itself, understanding the broader impact of right ventricular function and pulmonary artery dynamics is crucial for a comprehensive assessment of clinical efficacy and patient outcomes. A newly recognized index, right ventricular-pulmonary artery (RV-PA) coupling, reflects the RV's ability to handle pulmonary afterload and is associated with adverse outcomes. Purpose This meta-analysis consolidates findings from diverse studies to systematically evaluate the association between RV-PA coupling parameters and the success of mitral TEER. Methods We conducted a systematic literature search for studies assessing RV-PA coupling indices at baseline in patients undergoing mitral TEER. We recorded the year of publication, method of RV-PA assessment, and the proposed cutoffs. The primary outcome of interest was the combined primary endpoint of included studies at maximal follow-up and the adjusted hazard ratios of RV-PA uncoupling were extracted if they were available. Secondary outcomes included mortality and post-operative mitral regurgitation at follow-up. Pooling of the hazard ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being significant. Results We identified a total of 316 studies, of which 8 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All but one study utilized the Tricuspid Annular Plane Systolic Excursion/Pulmonary artery systolic pressure (TAPSE/PASP) as the method of RV-PA assessment. According to the results of the meta-analysis, the presence of baseline RV-PA uncoupling was associated with a 2.3-fold increased risk of facing the combined primary endpoint at maximal follow-up (Figure, Panel A). All-cause mortality was also approximately 2.2-fold higher in cases of RV-PA uncoupling (Figure, Panel B). Finally, post-operative MR was 1.4-fold higher in cases of RV-PA uncoupling (Figure, Panel C). Significant between-study heterogeneity was detected in all the examined endpoints. Conclusion: This meta-analysis indicates that RV-PA uncoupling at baseline represents an important prognostic marker in patients undergoing mitral TEER.Figure