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International Journal of Stroke :... Oct 2023Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of...
Risk of both intracranial hemorrhage and ischemic stroke in elderly individuals with nonvalvular atrial fibrillation taking direct oral anticoagulants compared with warfarin: Analysis of the ANAFIE registry.
BACKGROUND AND AIMS
Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real-world setting. We also determined the baseline characteristics associated with both ICH and ischemic stroke.
METHODS
Patients aged ⩾ 75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and ICH. Secondary endpoints included subtypes of ICH.
RESULTS
Of 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed ICH (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.70-0.97), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23).
CONCLUSION
Patients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage.
DATA ACCESS STATEMENT
The individual de-identified participant data and study protocol will be shared for up to 36 months after the publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to [email protected].
Topics: Aged; Humans; Female; Aged, 80 and over; Warfarin; Atrial Fibrillation; Stroke; Ischemic Stroke; Prospective Studies; Subarachnoid Hemorrhage; Treatment Outcome; Anticoagulants; Intracranial Hemorrhages; Cerebral Hemorrhage; Registries; Administration, Oral
PubMed: 37154598
DOI: 10.1177/17474930231175807 -
Journal of the American Heart... Dec 2023An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety...
BACKGROUND
An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure.
METHODS AND RESULTS
We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow-up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16-0.39] for apixaban, 0.23 [95% CI, 0.14-0.37] for dabigatran, 0.23 [95% CI, 0.09-0.60] for edoxaban, and 0.31 [95% CI, 0.21-0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18-0.35] for apixaban, 0.17 [95% CI, 0.11-0.25] for dabigatran, 0.31 [95% CI, 0.17-0.56] for edoxaban, and 0.31 [95% CI, 0.23-0.41] for rivaroxaban).
CONCLUSIONS
In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.
Topics: Humans; Warfarin; Atrial Fibrillation; Rivaroxaban; Dabigatran; Retrospective Studies; Anticoagulants; Stroke; Ischemic Stroke; Subarachnoid Hemorrhage; Vitamin K; Administration, Oral
PubMed: 38038171
DOI: 10.1161/JAHA.123.029979 -
The European Journal of Contraception &... Dec 2023abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical... (Review)
Review
BACKGROUND
abnormal uterine bleeding is a very frequent reason for referral to gynaecologists and can deeply influence the quality of life. Once organic causes requiring surgical treatment are ruled out, clinicians should be able to manage these patients conservatively in the most effective way.
MATERIALS AND METHODS
a search in PubMed/MEDLINE database was conducted in order to find relevant and recent meaningful sources for this narrative review.
RESULTS
LNG-IUS 52 mg is the first-line treatment for non-organic causes. Nevertheless, it could be contraindicated or declined by the patient. Combined oral contraceptives (COC) and progestin-only pills inhibit the hypothalamic-pituitary-ovarian axis, preventing ovulation, and induce endometrial atrophy. Consequently, they are effective in treating AUB. Moreover, brand new pills containing a combination of oestrogens, progestins and GnRH antagonists are now available for the management of AUB related to uterine fibroids.
CONCLUSIONS
In daily clinical practice, oral hormonal therapies are convenient and reversible tools to manage AUB when LNG-IUS 52 mg is contraindicated or turn down by the patient. Many oral hormonal therapies are prescribed to treat AUB, but only a few have been approved with this specific indication, therefore further large well-designed studies are necessary in order to compare the efficacy of different pills for treating AUB.
Topics: Female; Humans; Quality of Life; Progestins; Menorrhagia; Contraceptives, Oral, Combined; Leiomyoma; Uterine Hemorrhage; Levonorgestrel
PubMed: 37955241
DOI: 10.1080/13625187.2023.2270098 -
Future Cardiology Aug 2023Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding... (Review)
Review
Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding often dictate treatment decisions. Inhibition of the intrinsic coagulation system via factor XIa may allow for selective inhibition of the coagulation cascade without significantly impacting hemostasis after injury. Asundexian is an oral small molecule factor XIa inhibitor that, via this novel mechanism, may prove to be a safe and effective option compared with available anticoagulants. Early clinical data for asundexian was promising as a safer alternative to current therapies and prompted further analysis in certain patient populations at increased thrombotic risk. Currently, studies are ongoing to evaluate the safety and efficacy in stroke prevention in atrial fibrillation and in patients following an acute noncardioembolic ischemic stroke or high-risk transient ischemic attack.
Topics: Humans; Factor XIa; Anticoagulants; Warfarin; Hemorrhage; Thrombosis; Atrial Fibrillation; Stroke; Administration, Oral
PubMed: 37830334
DOI: 10.2217/fca-2023-0051 -
Current Opinion in Anaesthesiology Apr 2024Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. Thus, trauma care providers are facing a steadily raising number... (Review)
Review
PURPOSE OF REVIEW
Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. Thus, trauma care providers are facing a steadily raising number of injured patients on DOACs.
RECENT FINDINGS
Despite a predictable pharmacokinetic profile, the resulting plasma levels of trauma patients upon admission and bleeding risks remain uncertain. Therefore, recent guidelines recommend the measurement of DOAC plasma concentrations in injured patients. Alternatively, DOAC specific visco-elastic tests assays can be applied to identify DOAC patients at bleeding risk.Bleeding complications in trauma patients on DOACs are generally higher compared to nonanticoagulated subjects, but comparable to vitamin K antagonists (VKAs). In particular, a traumatic brain injury does not carry an increased risk of intracranial bleeding due to a DOAK intake compared to VKAs. Current studies demonstrated that up to 14% of patients with a hip fracture are on DOACs prior to surgery. However, the majority can be operated safely within a 24h time window without an increased bleeding rate.Specific antagonists facilitate rapid reversal of patients on DOACs. Idarucizumab for dabigatran, and andexanet alfa for apixaban and rivaroxaban have been approved for life threatening bleeding. Alternatively, prothrombin complex concentrate can be used. Dialysis is a potential treatment option for dabigatran and haemoabsorption with special filters can be applied in patients on FXa-inhibitors.
SUMMARY
Current guidelines recommend the measurement of DOAC plasma levels in trauma patients. Compared to VKAs, DOACs do not carry a higher bleeding risk. DOAC specific antagonists facilitate the individual bleeding management.
Topics: Humans; Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Rivaroxaban; Thromboembolism; Wounds and Injuries
PubMed: 38390987
DOI: 10.1097/ACO.0000000000001356 -
European Heart Journal. Cardiovascular... May 2024
Topics: Humans; Platelet Aggregation Inhibitors; Anticoagulants; Administration, Oral; Treatment Outcome; Hemorrhage; Risk Factors; Risk Assessment
PubMed: 38563454
DOI: 10.1093/ehjcvp/pvae021 -
Journal of Diabetes and Its... Aug 2023Diabetes represents a pro-thrombotic condition.
BACKGROUND
Diabetes represents a pro-thrombotic condition.
OBJECTIVES
The primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding.
METHODS
We enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding.
RESULTS
We did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients.
CONCLUSION
DOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus; Hemorrhage; Rivaroxaban; Stroke
PubMed: 37390799
DOI: 10.1016/j.jdiacomp.2023.108512 -
International Urology and Nephrology Jul 2023Thromboembolism (TE) is a common and serious complication of nephrotic syndrome (NS). NS is associated with hypercoagulability, which may be induced by changes in... (Review)
Review
Thromboembolism (TE) is a common and serious complication of nephrotic syndrome (NS). NS is associated with hypercoagulability, which may be induced by changes in coagulation, anticoagulant, and fibrinolytic factors. Moreover, accumulating evidence supports the hypothesis that the complex interactions between genetic and acquired risk factors in TE should be considered and that genetic susceptibility should not be ignored. Extracellular vesicles (EVs) also play unique roles. Further research on EVs may provide new insights into the discovery and treatment of TE associated with NS. The occurrence of NS accompanied by TE may be associated with various risk factors. Preventive anticoagulant therapy can not only reduce the risk of TE in patients but also aggravate the risk of bleeding. Heparin and vitamin K antagonists (VKAs), traditional anticoagulant drugs, have been extensively applied in the prevention and treatment of thromboembolic diseases, and emerging direct oral anticoagulants (DOACs) also provide an alternative choice. Owing to the particularity of NS, the safe application of DOACs still needs to be addressed. This review aimed to comprehensively describe the pathophysiology of TE in NS, as well as analyze the associated risk factors, the opportunity for preventive anticoagulation, and current anticoagulant information.
Topics: Humans; Nephrotic Syndrome; Thromboembolism; Anticoagulants; Hemorrhage; Heparin; Venous Thromboembolism; Administration, Oral; Vitamin K
PubMed: 36757656
DOI: 10.1007/s11255-023-03474-8 -
European Journal of Internal Medicine Oct 2023Direct oral anticoagulants (DOACs) are currently the first-choice therapy for the prevention of cardioembolic events in patients with atrial fibrillation and for the... (Review)
Review
Direct oral anticoagulants (DOACs) are currently the first-choice therapy for the prevention of cardioembolic events in patients with atrial fibrillation and for the treatment of venous thromboembolism (VTE) due to their more favorable efficacy to safety profile in comparison to vitamin K antagonists (VKA). DOACs did not show a clinical benefit when used for in stroke prevention in patients with mechanic or rheumatic valves or in those who underwent transcatheter aortic valve implantation (TAVI), in the treatment of VTE in patients with antiphospholipid antibody syndrome and in prevention of VTE in medically ill patients. There are some concerns for bleeding excess at the gastrointestinal site for some, but not all, DOACs. In recent years, in order to overcome the limitations of the available DOACs and to explore the advantages of anticoagulation in additional clinical settings, the development of factor XI and factor XII inhibitors as anticoagulant agents has been proposed. Emerging data show that factor XI has a minor role in the physiological process of hemostasis and an important role in the development of thrombosis. Bleeding has been viewed for several years as an unavoidable side effect of anticoagulant therapy. The aim of factor XI inhibitors is to challenge this dogma by favoring the uncoupling between hemostasis and thrombosis. This paper provides an update on the rationale for the use of factor XI inhibitors, their pharmacological properties and the preliminary clinical findings.
Topics: Humans; Factor XI; Venous Thromboembolism; Anticoagulants; Hemorrhage; Thrombosis; Administration, Oral
PubMed: 37544845
DOI: 10.1016/j.ejim.2023.08.001 -
The Journal of the American Academy of... Aug 2023There is wide variability in the management of patients on antithrombotic therapy requiring surgery of the hand and wrist. There are no specific guidelines regarding... (Review)
Review
There is wide variability in the management of patients on antithrombotic therapy requiring surgery of the hand and wrist. There are no specific guidelines regarding whether to temporarily cease or continue oral anticoagulants and antiplatelet agents. Discontinuation of these medications before surgery can lead to perioperative thromboembolic or ischemic events. On the other hand, continuation can lead to intraoperative or postoperative bleeding complications. This review discusses various anticoagulants and antiplatelet agents with special considerations for their management, analyzes the current literature, summarizes current recommendations, and provides direction for additional research.
Topics: Humans; Platelet Aggregation Inhibitors; Wrist; Anticoagulants; Postoperative Hemorrhage; Postoperative Complications
PubMed: 37478048
DOI: 10.5435/JAAOS-D-22-00751