Abstract:Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant hete… Show more
“…We found that the overall incidence of serious thrombotic/haemorrhagic events (mainly gastrointestinal) for all DOACs was very low compared to findings for warfarin [26,27]. We found no significant difference in the incidence of thrombotic complications between patients with normal/supranormal renal function and those with impaired renal function, nor did we find significant differences for post-dose anti-Xa activity, pre-dose anti-IIa activity, and plasma concentrations of edoxaban for patients with GFR <90 mL/min compared to patients with GFR �90 mL/min.…”
Background and purpose
Renal excretion of direct oral anticoagulants (DOACs) varies depending on the drug. Hypothetically, an increased glomerular filtration rate (GFR) may lead to suboptimal dosing and a higher thromboembolic events incidence. However, real-world patient data do not support the theoretical risk. The aim is to analyse DOAC outcomes in patients with normal and high (≥90 mL/min) GFR, focusing on biological parameters and thrombotic/haemorrhagic events.
Methods
Observational prospective single-centre study and registry of patients on DOACs. Follow-up was 1,343 patient-years. A bivariate analysis was performed of baseline variables according to GFR (<90 mL/min vs ≥90 mL/min). Anti-Xa activity before and after drug intake (HemosIL, Liquid Anti-Xa, Werfen) was measured for edoxaban, apixaban, and rivaroxaban; diluted thrombin time for dabigatran (HEMOCLOT); and additionally, plasma concentrations in edoxaban (HemosIl, Liquid Anti-Xa suitably calibrated).
Results
1,135 patients anticoagulated with DOACs were included and 152 patients with GFR ≥90 mL/min. Of 18 serious thrombotic complications during follow-up, 17 occurred in patients with GFR <90 mL/min, and 1 in a patient with GFR ≥90 mL/min. A higher incidence of complications was observed in patients with normal GFR, but the difference was not statistically significant (p>0.05). No statistically significant differences with clinical relevance were observed between the normal or supranormal groups in anti-Xa activity or in edoxaban plasma concentrations.
Conclusions
There was no increased incidence of thrombotic/haemorrhagic complications in our patients treated with DOACs, including 66% treated with edoxaban, and patients with GFR ≥90 mL/min. Likewise, drug anti-Xa activity and edoxaban plasma concentration did not seem to be influenced by GFR.
“…We found that the overall incidence of serious thrombotic/haemorrhagic events (mainly gastrointestinal) for all DOACs was very low compared to findings for warfarin [26,27]. We found no significant difference in the incidence of thrombotic complications between patients with normal/supranormal renal function and those with impaired renal function, nor did we find significant differences for post-dose anti-Xa activity, pre-dose anti-IIa activity, and plasma concentrations of edoxaban for patients with GFR <90 mL/min compared to patients with GFR �90 mL/min.…”
Background and purpose
Renal excretion of direct oral anticoagulants (DOACs) varies depending on the drug. Hypothetically, an increased glomerular filtration rate (GFR) may lead to suboptimal dosing and a higher thromboembolic events incidence. However, real-world patient data do not support the theoretical risk. The aim is to analyse DOAC outcomes in patients with normal and high (≥90 mL/min) GFR, focusing on biological parameters and thrombotic/haemorrhagic events.
Methods
Observational prospective single-centre study and registry of patients on DOACs. Follow-up was 1,343 patient-years. A bivariate analysis was performed of baseline variables according to GFR (<90 mL/min vs ≥90 mL/min). Anti-Xa activity before and after drug intake (HemosIL, Liquid Anti-Xa, Werfen) was measured for edoxaban, apixaban, and rivaroxaban; diluted thrombin time for dabigatran (HEMOCLOT); and additionally, plasma concentrations in edoxaban (HemosIl, Liquid Anti-Xa suitably calibrated).
Results
1,135 patients anticoagulated with DOACs were included and 152 patients with GFR ≥90 mL/min. Of 18 serious thrombotic complications during follow-up, 17 occurred in patients with GFR <90 mL/min, and 1 in a patient with GFR ≥90 mL/min. A higher incidence of complications was observed in patients with normal GFR, but the difference was not statistically significant (p>0.05). No statistically significant differences with clinical relevance were observed between the normal or supranormal groups in anti-Xa activity or in edoxaban plasma concentrations.
Conclusions
There was no increased incidence of thrombotic/haemorrhagic complications in our patients treated with DOACs, including 66% treated with edoxaban, and patients with GFR ≥90 mL/min. Likewise, drug anti-Xa activity and edoxaban plasma concentration did not seem to be influenced by GFR.
“…The thrombin inhibitor dabigatran was the DOAC with the strongest reduction in intracranial bleeding compared with warfarin (HR = 0.40 [0.27–0.60], P < 0.001) (Connolly et al, 2009), followed by the Factor Xa inhibitors apixaban (HR = 0.42 [0.30–0.58], P < 0.001) (Granger et al, 2011), edoxaban (HR = 0.47 [0.34–0.63], P < 0.001) (Giugliano et al, 2013) and rivaroxaban (HR = 0.67 [0.47–0.93], P = 0.02) (Patel et al, 2011). Interestingly, a recent meta‐analysis in anticoagulated octogenarians with non‐valvular AF showed that, besides the significant reduction in all‐cause mortality in those treated with DOACs compared with those treated with warfarin, there was also a 43% reduction of intracranial bleeding (Bonanad et al, 2021), pointing to DOACs as a safe and effective alternative for the elderly. Additionally, the most widely used DOACs ‐ dabigatran, apixaban and rivaroxaban ‐ already have antidotes available, in case severe or life‐threatening bleeding occurs and anticoagulation needs to be reversed immediately (White et al, 2022).…”
Section: Is An Anticoagulant Therapy Plausible For Ad?mentioning
confidence: 99%
“…Interestingly, a recent meta-analysis in anticoagulated octogenarians with non-valvular AF showed that, besides the significant reduction in all-cause mortality in those treated with DOACs compared with those treated with warfarin, there was also a 43% reduction of intracranial bleeding (Bonanad et al, 2021), pointing to DOACs as a safe and effective alternative for the elderly. Additionally, the most widely used DOACs -dabigatran, apixaban and rivaroxaban -already have antidotes available, in case severe or life-threatening bleeding occurs and anticoagulation needs to be reversed immediately (White et al, 2022).…”
Section: Is An Anticoagulant Therapy Plausible For Ad?mentioning
Alzheimer's disease (AD) and cardiovascular disease (CVD) are strongly associated. Both are multifactorial disorders with long asymptomatic phases and similar risk factors. Indeed, CVD signatures such as cerebral microbleeds, micro‐infarcts, atherosclerosis, cerebral amyloid angiopathy and a procoagulant state are highly associated with AD. However, AD and CVD co‐development and the molecular mechanisms underlying such associations are not understood. Here, we review the evidence regarding the vascular component of AD and clinical studies using anticoagulants that specifically evaluated the development of AD and other dementias. Most studies reported a markedly decreased incidence of composite dementia in anticoagulated patients with atrial fibrillation, with the highest benefit for direct oral anticoagulants. However, sub‐analyses by differential dementia diagnosis were scarce and inconclusive. We finally discuss whether anticoagulation could be a plausible preventive/therapeutic approach for AD and, if so, which would be the best drug and strategy to maximize clinical benefit and minimize potential risks.
“…Además, en estos ensayos clínicos los pacientes ancianos suelen ser un grupo muy seleccionado, con poca representación de pacientes geriátricos frágiles y con riesgo de caídas. Un metanálisis de la evidencia actualmente disponible del subanálisis de ensayos clínicos y cohortes del mundo real refrendó la eficacia y seguridad de ACOD frente a AVK en octogenarios con FA, y asoció reducciones significativas en ACV, mortalidad por cualquier causa y hemorragia intracraneal 29 . Figura 1 Tratamiento anticoagulante en pacientes ancianos con fibrilación auricular.…”
Section: Fibrilación Auricular En El Paciente Ancianounclassified
Los fármacos antitrombóticos son un pilar fundamental en el tratamiento y prevención de las enfermedades cardiovasculares. A pesar de la amplia experiencia previa, en los últimos años se han producido importantes novedades en la práctica clínica que han modificado estrategias terapéuticas en diferentes escenarios como en el campo de la fibrilación auricular, la cardiopatía isquémica o el intervencionismo coronario percutáneo. A todo esto se debe que añadir el papel fundamental del tratamiento antitrombótico durante la reciente pandemia de COVID-19 y sus implicaciones dado el estado protrombótico que produce la infección por el virus SARS-CoV-2. Desde el Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología, se ha sintetizado la evidencia científica reciente en el presente documento.
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