Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known <i>consequence</i> of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known 'risk factors' for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.
Banerjee M, Pal R, Maisnam I, et al. <b>Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: a meta-analysis and meta-regression of randomized controlled trials.</b> Diabetes Obes Metab. 2023;25:2697-2703. 37334516.
Source Citation Major Extremity Trauma Research Consortium (METRC); O’Toole RV, Stein DM, O’Hara NN, et al. Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture. N Engl J Med. 2023;388:203-213. 36652352
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Abstract Background Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program. Methods Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation. Results Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02). Conclusion In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence. Acknowledgement/Funding The GLORIA-AF Registry program was funded by Boehringer-Ingelheim
Personalized management, identification of risk factors and shared-decision making are crucial in improving the best medical therapy for patients with PAD. Further studies are needed to assess the long-term safety and efficacy of novel strategies in real-world patients.