Safety Outcomes Research Articles

Data Quality in State Registry Reports of Medical Cannabis Patients in the United States.

Objectives. To investigate characteristics of data reported in US medical cannabis registries across states. Methods. Data included 2021 medical cannabis registry reports from 34 states, Puerto Rico, and the District of Columbia (hereafter, states) with active medical cannabis programs. The data from the reports were manually coded into domains and subcategories, including information related to patients (e.g., number, demographics), authorizing clinicians, sales (e.g., content, revenue), license tracking, and health and safety outcomes. Results. Among 36 states, 97% reported total patient number and 75% reported number of authorizing clinicians. Least reported subcategories included patient race/ethnicity (8%), adverse events (11%), therapeutic benefits (6%), and product recalls (6%). States that recently legalized medical cannabis (2013-2018) reported a higher number of subcategories overall, with a median of 11 versus 8 for early adopting states (1996-2012). More medical-use states reported data on authorizing clinicians compared with nonmedical adult-use states but were otherwise similar. Conclusions. Medical cannabis state registries generally reported data on consumers, clinicians, and sales rather than health and safety outcomes. More comprehensive and uniform medical cannabis public health surveillance is needed. (Am J Public Health. 2024;114(S8):S685-S693. https://doi.org/10.2105/AJPH.2024.307728).

Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial

Tenecteplase has potential benefits over alteplase, the standard agent for intravenous thrombolysis in acute ischaemic stroke, because it is administered as a single bolus and might have superior efficacy. The ATTEST-2 trial investigated whether tenecteplase was non-inferior or superior to alteplase within 4·5 h of onset. We undertook a prospective, randomised, parallel-group, open-label trial with masked endpoint evaluation in 39 UK stroke centres. Previously independent adults with acute ischaemic stroke, eligible for intravenous thrombolysis less than 4·5 h from last known well, were randomly assigned 1:1 to receive intravenous alteplase 0·9 mg/kg or tenecteplase 0·25 mg/kg, by use of a telephone-based interactive voice response system. The primary endpoint was the distribution of the day 90 modified Rankin Scale (mRS) score and was analysed using ordinal logistic regression in the modified intention-to-treat population. We tested the primary outcome for non-inferiority (odds ratio for tenecteplase vs alteplase non-inferiority limit of 0·75), and for superiority if non-inferiority was confirmed. Safety outcomes were mortality, symptomatic intracranial haemorrhage, radiological intracranial haemorrhage, and major extracranial bleeding. The trial was prospectively registered on ClinicalTrials.gov (NCT02814409). Between Jan 25, 2017, and May 30, 2023, 1858 patients were randomly assigned to a treatment group, of whom 1777 received thrombolytic treatment and were included in the modified intention-to-treat population (n=885 allocated tenecteplase and n=892 allocated alteplase). The mean age of participants was 70·4 (SD 12·9) years and median National Institutes of Health Stroke Scale was 7 (IQR 5-13) at baseline. Tenecteplase was non-inferior to alteplase for mRS score distribution at 90 days, but was not superior (odds ratio 1·07; 95% CI 0·90-1·27; p value for non-inferiority<0·0001; p=0·43 for superiority). 68 (8%) patients in the tenecteplase group compared with 75 (8%) patients in the alteplase group died, symptomatic intracerebral haemorrhage (defined by SITS-MOST criteria) occurred in 20 (2%) versus 15 (2%) patients, parenchymal haematoma type 2 occurred in 37 (4%) versus 26 (3%) patients, post-treatment intracranial bleed occurred in 94 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six (1%) patients, respectively, and angioedema occurred in six (1%) participants in both groups. Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase. The Stroke Association and British Heart Foundation.

Efficacy and Safety of Somapacitan Relative to Somatrogon and Lonapegsomatropin in Pediatric Growth Hormone Deficiency: Systematic Literature Review and Network Meta-analysis.

Since direct comparisons of long-acting growth hormones (LAGHs) are lacking, analyses were performed to indirectly compare the efficacy and safety of somapacitan versus somatrogon and lonapegsomatropin in children with growth hormone deficiency (GHD). A systematic literature review (SLR) identified studies of once-weekly LAGHs for the treatment of pediatric GHD. Indirect comparisons (ICs) using a Bayesian hierarchical network meta-analysis and a random effects model were performed using daily growth hormone (GH) 0.034mg/kg/day (base case) or 0.024-0.034mg/kg/day (alternative analyses) as the common comparator to compare height outcomes to 52weeks [annualized height velocity, height velocity standard deviation score (SDS), and height SDS]. Identified evidence did not allow IC of safety or longer-term efficacy outcomes so these were qualitatively described. The SLR identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only), and one lonapegsomatropin trial comparing the LAGH with daily GH in treatment-naïve pre-pubertal children for IC. ICs revealed no differences at 52weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH, with respect to all growth outcomes considered in children with GHD. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily GH, with the exception of observed injection site pain for somatrogon. No efficacy and safety differences were identified in comparisons of once weekly somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH. All treatments were generally well tolerated, with the exception of observed injection site pain for somatrogon.

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Management and monitoring of anesthesia during the perioperative period in a Tertiary Hospital in Bangladesh

Background: Anesthesia management is crucial for ensuring patient safety and optimal surgical outcomes during the perioperative period. In Bangladesh, the challenges faced in managing and monitoring anesthesia in tertiary care hospitals necessitate a comprehensive evaluation of current practices. This study aims to assess the anesthetic management protocols and monitoring strategies employed in a tertiary hospital in Bangladesh. Methods: This observational study was conducted in Islami Bank Medical College Hospital, Rajshahi, Bangladesh from July to December 2023. Data were collected from patients undergoing various surgical procedures requiring anesthesia. The anesthetic techniques used, intraoperative monitoring parameters, and any complications encountered were recorded. The study included a review of anesthesia charts, patient records, and interviews with anesthesia providers. Statistical analysis was performed to identify trends and correlations. Results: A total of 200 patients were included in the study. The most commonly used anesthetic technique was general anesthesia (65%), followed by regional anesthesia (30%) and local anesthesia (5%). Intraoperative monitoring parameters included heart rate, blood pressure, oxygen saturation, and end-tidal carbon dioxide levels, which were consistently documented in 95% of cases. Complications occurred in 10% of patients, primarily involving respiratory issues and cardiovascular instability. Proper adherence to monitoring protocols significantly reduced the incidence of complications. Conclusion: Effective management and monitoring of anesthesia during the perioperative period are vital for patient safety in a tertiary hospital setting. The study highlights the importance of standardized protocols and continuous monitoring to minimize complications. Recommendations for improving anesthetic practices include regular training for anesthesia providers and enhancing monitoring infrastructure to ensure optimal patient care.

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.

Comparative Analysis of Safety and Efficacy Between Anterior and Posterior Calyceal Entry in Supine Percutaneous Nephrolithotomy.

Introduction: One advantage of supine percutaneous nephrolithotomy (sPCNL) is the ability to access anterior as well as posterior calyces, but the safety and efficacy of anterior calyceal entry has never been investigated to our knowledge. We prospectively evaluated patients scheduled for sPCNL comparing anterior and posterior calyceal access. Materials and Methods: After Institutional Review Board approval, we prospectively enrolled 100 consecutive patients undergoing sPCNL from February to September 2023. Primary outcomes included intraoperative complications, blood transfusions, 30-day complication rates, and emergency department (ED) visits or readmissions. Secondary outcomes included stone-free rates (SFR). Results: Seventy-six patients had anterior calyceal entry and 24 had posterior. No significant differences were found in terms of baseline demographics (age, body mass index), stone characteristics (location, density, complexity), or intraoperative features (operative time, location of access). Safety outcomes, including intraoperative complications (1% vs 4%), blood transfusions (3% vs 8%), 30-day complication rates (17% vs 21%), and ED visits (1% vs 0) or readmissions (11% vs 21%) were comparable between groups. Overall SFRs were equivalent (86% vs 90%). Conclusion: We found that anterior and posterior accesses in sPCNL offer similar safety and efficacy, with no significant differences in complications or SFRs. Surgeons can select either approach based on patient anatomy and surgical needs without concern for increased complications. Further research is necessary to confirm these findings and guide best practices for calyx selection in sPCNL.

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.

Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials

Abstract Background Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a). Purpose We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia. Methods A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy. Results A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels. Conclusions PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels

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 (&amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;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 &amp;lt;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.

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF &amp;gt;40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of &amp;gt; 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

Safety and mid-term outcomes of impella compared to intra-aortic balloon pumping in patients who required mechanical cardiac support

Abstract Background Impella (Abiomed USA) is a promising alternative to improve prognosis in patients with cardiogenic shock requiring mechanical cardiac support (MCS). Despite of its advanced hemodynamic profile, its superiority regarding prognosis has not been established yet. Aims The aims of this study were to investigate safety and mid-term outcomes of Impella compared to IABP in patients who required MCS. Methods In this single-center study, consecutive 205 patients who required IABP or Impella from January 2017 to June 2023 were evaluated retrospectively. The primary outcome was 180-day mortality. Secondary outcomes were the rate of complications including hemolysis, thrombocytopenia, bleeding, limb ischemia, acute kidney impairment and stroke. Major complication was defined as major bleeding (BARC 3-5), limb ischemia and stroke. Results Of all patients, 62 (30.2%) received Impella and 143 (69.8%) IABP. The rate of patients required extracorporeal membrane oxygenation (ECMO) support was not significantly different between two groups (31.4 % vs 38.7%; p=0.34. There were no significant differences in 180-day mortality between two groups (36.2% vs 31.1%; p=0.55). Further investigation according to SCAI classification demonstrated that the mortality rate in SCAI C group was significantly lower in Impella than IABP group (34.1% vs 6.7%; p=0.02), whereas there were not significant differences in mortality between two groups in SCAI D and E groups (54.8% vs 61.4%; p=0.71). The rate of major complications was significantly higher in Impella group (54.4% vs 72.1%; p=0.02). The rate of hemolysis (19.6% vs. 58.1%, p&amp;lt;0.01), thrombocytopenia (19.6% vs. 58.1%, p&amp;lt;0.01), limb ischemia (4.3% vs. 17.7%, p&amp;lt;0.01), acute kidney impairment (37.7% vs 64.5%, p&amp;lt;0.01) and initiation of renal replacement therapy (13.8% vs 29%, p=0.02) were significantly higher in Impella group. Multivariate analysis adjusting for Impella use, out of hospital cardiopulmonary arrest (OHCPA), initial lactate ≥60 md/dL and major complication, revealed that age ≥70 (hazard ratio (HR): 3.1, 95%CI: 1.73-5.61) and use of ECMO (HR: 4.3, 95%CI: 2.54-7.31) were independent predictor of mortality. The mortality rate arose up to 83.3% in patients with age ≥70, OHCPA and use of ECMO (HR: 9.7, 95%CI: 4.07-23.02). Conclusion The mortality rate did not differ between Impella and IABP, however Impella was associated with improved mortality in patients with SCAI C group. The complications were high likely seen in patients with Impella compared to IABP. Our findings indicate that Impella results in better outcomes with careful selection of patients, defining its indication and appropriate care. A further investigation would be of value to elucidate whether Impella improve prognosis.

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&amp;lt;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.

Vericiguat in heart failure patients: analyzing safety, tolerability, and quality of life via meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) poses a significant burden on global healthcare systems, necessitating effective therapeutic interventions. Vericiguat, a novel agent targeting soluble guanylate cyclase, has emerged as a potential treatment for HF. Purpose To understand its impact on patient outcomes, including safety, tolerability, and quality of life (QoL). Methods A comprehensive meta-analysis was conducted, encompassing four randomized controlled trials (RCTs) identified through Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science databases up to December 1, 2023. The primary efficacy outcome, Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS), and the primary safety outcome, drug-related serious adverse events (AEs), were analyzed. Pooled mean differences (MD) and risk ratios (RR) were calculated using inverse variance common-effect model. Results The meta-analysis encompassed 5947 patients across the four RCTs. Our findings indicated that vericiguat did not demonstrate a significant beneficial effect on KCCQ-OSS (MD -0.13, 95% CI -1.32 to 1.05), suggesting no substantial impact on overall QoL, despite a statistically significant improvement in the KCCQ-Physical Limitation Score (PLS) (MD 3.74, 95% CI 0.24 to 7.24) compared to placebo. Notably, vericiguat exhibited a favorable safety and tolerability profile, with comparable risk for AEs leading to death (RR 1.32, 95%CI, 0.58 to 3.03), withdrawal due to AEs (RR 1.08, 95% CI 0.88 to 1.32) or serious AEs (RR 1,18, 95%CI, 0,50; 2,80), renal and urinary disorders (RR 0.99, 95% CI 0.88 to 1.11), symptomatic hypotension (RR 1.17, 95% CI 0.98 to 1.40), and acute kidney injury (RR 1.04, 95% CI 0.83 to 1.31) compared to placebo. Conclusion Vericiguat demonstrates promising safety and tolerability profiles in patients with HF. While our analysis reveals significant improvement in KCCQ-PLS, indicating enhanced physical limitation scores, the lack of statistically significant impact on overall QoL raises questions about its comprehensive efficacy. These findings underscore the need for further research to elucidate the holistic impact of vericiguat on patient-reported outcomes in heart failure management.Forest plot of quality of life outcomesForest plot of safety outcomes

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 &amp;lt;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&amp;lt;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.

Comparative outcomes of drug-coated balloon angioplasty versus second-generation drug-eluting stent for in-stent restenosis: a real-world data analysis

Abstract Background Coronary in-stent restenosis (ISR) poses a significant challenge in interventional cardiology, with optimal treatment strategies being the subject of ongoing debate. Current clinical guidelines offer a choice between drug-coated balloon angioplasty (DCB) and repeat stenting with second-generation drug-eluting stents (DES), each with distinct implications for long-term patient outcomes. Purpose The aim of this study is to compare 1-year outcomes between DCB angioplasty and second-generation DES in the treatment of ISR. Longitudinal real-world data are used from the OBSERVABLE database, which comprises German health claims data between 2012 and 2021. Methods A total of 10,440 ISR individuals undergoing DCB or DES intervention were identified. After exclusion of bare-metal stents, first generation stents and non-DCBs, 3,810 propensity score-matched individuals remained. The primary outcome was the composite of all-cause mortality and myocardial infraction (MI). Secondary outcomes included all-cause death, MI, and bleeding as a safety outcome. Results At 1-year follow-up, the primary outcome of all-cause mortality and MI was observed in 246 individuals (12.9%) in the DES group, compared with 201 individuals (10.6%) in the DCB group (HR, 1.27; 95% CI, 1.06-1.53). Sensitivity analysis confirmed the robustness of these findings. Secondary outcomes revealed higher all-cause mortality in the DES group (7.9%) compared to the DCB group (6.3%) (HR, 1.31; 95% CI, 1.03-1.66), with no difference in MI. Bleeding events were comparable between the two treatments, with 244 individuals (12.8%) in the DES group and 206 individuals (10.8%) in the DCB group (HR, 1.17; 95% CI, 0.89-1.53). Conclusion This real-world data analysis demonstrated a higher incidence of the primary composite endpoint of all-cause mortality and MI within one year, after treatment with DES compared to DCB. Our results support prior findings about the safety profile of repeated DES implantation and strengthen DCB as a potential superior alternative to DES in ISR management.

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&amp;lt;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.

Complication comparison in intermediate-to-high risk venous thromboembolism patients, treated with high vs standard dose apixaban and rivaroxaban after low molecular weight heparin

Abstract Background In patients with intermediate-to-high risk venous thromboembolism (VTE), current guidelines recommend initial treatment with low molecular weight heparin (LMWH), followed by an oral anticoagulant. However, the studies supporting these guidelines have only focused on the use of Edoxaban and Dabigatran after 5 days of LMWH treatment. To date there are no studies supporting similarly implemented guidelines for Apixaban and Rivaroxaban. Purpose To investigate the incidence of bleeding complications and thrombosis in intermediate-to-high risk VTE patients, when treated with either lead-in high or standard dose Rivaroxaban or Apixaban, following initial LMWH treatment. Methods Through a real-life retrospective study of 844 intermediate-to-high risk VTE patients, 584 were initially treated with LMWH and subsequently Apixaban or Rivaroxaban and divided into two groups. The first group of 514 patients, received high dose Apixaban or Rivaroxaban (10mg x 2 for 7 days and 15mg x 2 for 21 days respectively) before being reduced to their standard doses. The remaining 70 patients, instead transitioned directly to the standard doses (5mg x 2 and 20mg x 1 respectively) from LMWH. All patients started treatment between 2018 and 2023, and all complications were recorded until one year following initiation of treatment. Treatment complications include recurrent VTE, separated into deep vein thrombosis and pulmonary embolism, and bleeding complications in the form of fatal, non-fatal, minor and a drop in haemoglobin. The recurrence of VTE and incidence of bleeding complications were evaluated as the primary efficacy outcome and safety outcome respectively. Results Overall, 4.7% of patients treated with initial high dose Apixaban or Rivaroxaban suffered major bleeding complications as opposed to 2.9% treated with the standard dose (p=&amp;lt;0.05). Out of all complications, 5 were fatal, all of which were part of the high dose group and included 3 cerebral and 2 gastrointestinal bleeds. However, minor bleeding complications were more frequent in the standard dose group, presenting in 26.1% of patients, while, paradoxically, the high dose group had similar complications in only 15.8% of patients (p=&amp;lt;0.05). Although treated with a higher dose, 6/478 (1,26%) incurred a recurrent thrombus within a year of treatment, while the standard dose group had no cases of recurrence, though this was not a statistically significant result. Conclusion Directly transitioning from LMWH to standard dose Apixaban/Rivaroxaban in intermediate-to-high risk VTE, leads to a statistically significant reduced incidence of major bleeding complications, without an increased risk of recurrent thrombosis.

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

Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design

Abstract Introduction Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health. Purpose To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF. Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025. Conclusions The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design