Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias.

BACKGROUND: The management of anticoagulation therapy around the time of catheter ablation (CA) procedure for adults with arrhythmia is critical and yet is variable in clinical practice. The ideal approach for safe and effective perioperative management should balance the risk of bleeding during uninterrupted anticoagulation while minimising the risk of thromboembolic events with interrupted therapy. OBJECTIVES: To compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and SCI-Expanded on the Web of Science for randomised controlled trials on 5 January 2021. We also searched three registers on 29 May 2021 to identify ongoing or unpublished trials. We performed backward and forward searches on reference lists of included trials and other systematic reviews and contacted experts in the field. We applied no restrictions on language or publication status. SELECTION CRITERIA: We included randomised controlled trials comparing uninterrupted anticoagulation with any modality of interruption with or without heparin bridging for CA in adults aged 18 years or older with arrhythmia. DATA COLLECTION AND ANALYSIS: Two review authors conducted independent screening, data extraction, and assessment of risk of bias. A third review author resolved disagreements. We extracted data on study population, interruption strategy, ablation procedure, thromboembolic events (stroke or systemic embolism), major and minor bleeding, asymptomatic thromboembolic events, cardiovascular and all-cause mortality, quality of life (QoL), length of hospital stay, cost, and source of funding. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: We identified 12 studies (4714 participants) that compared uninterrupted periprocedural anticoagulation with interrupted anticoagulation. Studies performed an interruption strategy by either a complete interruption (one study) or by a minimal interruption (11 studies), of which a single-dose skipped strategy was used (nine studies) or two-dose skipped strategy (two studies), with or without heparin bridging. Studies included participants with a mean age of 65 years or greater, with only two studies conducted in relatively younger individuals (mean age less than 60 years). Paroxysmal atrial fibrillation (AF) was the primary type of AF in all studies, and seven studies included other types of AF (persistent and long-standing persistent). Most participants had CHADS2 or CHADS2-VASc demonstrating a low-moderate risk of stroke, with almost all participants having normal or mildly reduced renal function. Ablation source using radiofrequency energy was the most common (seven studies). Ten studies (2835 participants) were conducted in East Asian countries (Japan, China, and South Korea), while the remaining two studies were conducted in the USA. Eight studies were conducted in a single centre. Postablation follow-up was variable among studies at less than 30 days (three studies), 30 days (six studies), and more than 30 days postablation (three studies). Overall, the meta-analysis showed high uncertainty of the effect between the interrupted strategy compared to uninterrupted strategy on the primary outcomes of thromboembolic events (risk ratio (RR) 1.76, 95% confidence interval (CI) 0.33 to 9.46; I2 = 59%; 6 studies, 3468 participants; very low-certainty evidence). However, subgroup analysis showed that uninterrupted vitamin A antagonist (VKA) is associated with a lower risk of thromboembolic events without increasing the risk of bleeding. There is also uncertainty on the outcome of major bleeding events (RR 1.10, 95% CI 0.59 to 2.05; I2 = 6%; 10 studies, 4584 participants; low-certainty evidence). The uncertainty was also evident for the secondary outcomes of minor bleeding (RR 1.01, 95% CI 0.46 to 2.22; I2 = 87%; 9 studies, 3843 participants; very low-certainty evidence), all-cause mortality (RR 0.34, 95% CI 0.01 to 8.21; 442 participants; low-certainty evidence) and asymptomatic thromboembolic events (RR 1.45, 95% CI 0.85 to 2.47; I2 = 56%; 6 studies, 1268 participants; very low-certainty evidence). There was a lower risk of the composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality) in the interrupted compared to uninterrupted arm (RR 0.23, 95% CI 0.07 to 0.81; 1 study, 442 participants; low-certainty evidence). In general, the low event rates, different comparator anticoagulants, and use of different ablation procedures may be the cause of imprecision and heterogeneity observed. AUTHORS' CONCLUSIONS: This meta-analysis showed that the evidence is uncertain to inform the decision to either interrupt or continue anticoagulation therapy around CA procedure in adults with arrhythmia on outcomes of thromboembolic events, major and minor bleeding, all-cause mortality, asymptomatic thromboembolic events, and a composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality).  Most studies in the review adopted a minimal interruption strategy which has the advantage of reducing the risk of bleeding while maintaining a lower level of anticoagulation to prevent periprocedural thromboembolism, hence low event rates on the primary outcomes of thromboembolism and bleeding. The one study that adopted a complete interruption of VKA showed that uninterrupted VKA reduces the risk of thromboembolism without increasing the risk of bleeding. Hence, future trials with larger samples, tailored to a more generalisable population and using homogeneous periprocedural anticoagulant therapy and ablation source are required to address the safety and efficacy of the optimal management of anticoagulant therapy prior to ablation.

Knowledge, Attitude, and Practice Towards COVID-19 Among Pharmacists: A Cross-Sectional Study.

PURPOSE: The COVID-19 outbreak has caused governments to put pandemic-related guidelines requiring compliance and understanding by healthcare professionals to mitigate its spread uncontrollably. We studied pharmacists' knowledge, attitude, and practice towards the COVD-19 outbreak compared with other healthcare workers during the pandemic in Saudi Arabia. METHODS: We surveyed pharmacists' socio-demographics (n=50) compared with other healthcare professionals (n=378) during lockdown starting in June 2020. We measured respondents' level of knowledge (n=10 questions, maximum score of 10), attitude (n=17 questions, maximum score of 80), and their practices (n=16 questions, maximum score of 80) towards COVID-19 infection. RESULTS: Median knowledge score was 8 (25th-75th percentiles: 7-9), attitude score 76 (70-80) and practice score 74 (68-78). Good knowledge predictors were >20 years working experience [OR: 2.05 (95% CI: 1.03-4.06); P=0.04] and >50% working in clinical practice [OR: 1.72 (95% CI: 1.12-2.66); P=0.01], in inverse relationship with paramedical professions [OR: 0.45 (95% CI: 0.45 (0.28-0.72)); P=0.001] and working in a university hospital [OR: 0.51 (95% CI: 0.33. 0.81); P=0.004]. Availability of pharmaceutical information and treatment options was associated with good attitude [OR: 2.19 (95% CI: 1.04-4.59); P=0.039] and acquaintance as primary information sources negatively associated with good attitude [OR: 0.34 (95% CI: 0.15-0.8); P=0.013]. Good practice predictors were female gender [OR: 3.84 (95% CI: 2.37-6.24); P<0.001], military hospital employment [OR: 2.32 (95% CI: 1.25-4.31); P=0.008], USA [OR: 3.41 (95% CI: 1.03-11.22); P=0.044] or UK [OR: 8.86 (95% CI: 1.91-41.07); P=0.005] qualifications, and information on supportive measures [OR: 2.2 (95% CI: 1.36-3.56); P=0.001]. CONCLUSION: Health workers displayed good knowledge about COVID-19, while profession and working experience predicted adequate knowledge, positive attitude, or practice towards disease management.

Modulation of Circulating Trimethylamine N-Oxide Concentrations by Dietary Supplements and Pharmacological Agents: A Systematic Review.

Discovery of the association of plasma/serum trimethylamine N-oxide (TMAO) concentrations with atherosclerosis has sparked immense interest in exploring TMAO as a predictor of cardiovascular disease risk. A spectrum of antibiotics and other therapeutic strategies have been employed to test their potential to modulate TMAO concentrations, assuming the gut microbiome to be the key source of TMAO. The aim of this systematic review was to determine whether dietary supplements or pharmacological agents affect TMAO concentrations in adults. Six databases were searched (Medline, EMBASE, CINAHL, Scopus, ProQuest, and PubMed) for randomized and nonrandomized controlled trials. Searches were limited to the English language and to studies in adults. Thirteen eligible trials were identified, including 6 studies on dietary supplements and 7 on pharmacological agents. Whereas intervention studies involving dietary supplements were mostly randomized controlled trials, those involving pharmacological agents appeared opportunistic and varied greatly in study design and duration. Different interventional products were tested, and the studies lacked the consistency to reliably synthesize any evidence for the modifiability of TMAO concentrations by dietary supplements or pharmacological agents. Choline and l-carnitine are conditionally essential nutrients, and carefully designed placebo-controlled randomized trials specifically aimed at reducing the synthesis of microflora-dependent TMAO production from choline-containing precursors by pro- and/or prebiotics, antibiotics, or other pharmaceutical agents may be the way forward for future research.