Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

Diener, Hans Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John W.; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

doi:10.1093/eurheartj/ehv643

Cited by 64 publications

(66 citation statements)

References 76 publications

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“…It has been shown that adding aspirin in addition to oral anticoagulant therapy in patients with AF and stable coronary artery disease or history of stroke/TIA does not provide additional clinical benefit. [13][14][15] This suggests that avoiding unnecessary aspirin could be a strategy to reduce ICH risk. Other risk factors associated with ICH were older age, prior stroke/TIA, and enrollment in Asia or Latin America.…”

Section: Discussionmentioning

confidence: 99%

Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy

Lopes

Guimarães

Kolls

et al. 2017

Blood

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Key Points• Nearly 80% of the warfarintreated patients with ICH had an INR within or below therapeutic range around 2 weeks before the event.• We can reduce ICH by using apixaban rather than warfarin and by avoiding concomitant aspirin, especially in patients with older age.We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received ‡1 dose of the study drug (n 5 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was ‡4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban-and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as

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Section: Discussionmentioning

confidence: 99%

Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy

Lopes

Guimarães

Kolls

et al. 2017

Blood

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“…In a recent consensus document, published on the European Heart Journal [16,17], the Authors give suggestions, based on the results of phase III trials or, if unavailable, on expert opinion, for chosing the drug and/or dose for particular subgroups of patients. In particular, apixaban 5 mg twice daily is recommended as first choice for patients with AF and high risk of gastrointestinal bleeding, chronic kidney failure (creatinine clearance 30-49 ml/min) or older than 75 years .…”

Section: Estimating the Cost-effectiveness Of Treatment For Preventiomentioning

confidence: 99%

Estimating the cost-effectiveness of treatment for prevention of thromboembolic events in at-risk adults with non-valvular atrial fibrillation

Bellone¹,

Pradelli²,

2018

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INTRODUCTION: The direct oral anticoagulants (DOACs) have demonstrated a more predictable effect and a more favorable risk-benefit ratio compared to the standard oral anticoagulant treatment for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF).AIM: To estimate the efficiency of DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban vs. warfarin), in the prevention of clinical events in adult patients with NVAF.METHODS: A deterministic incremental cost-effectiveness analysis was performed to evaluate the avoidance of a clinical event and the incremental cost per avoided clinical event, in a hypothetical population of 100,000 adult patients with NVAF, over 1-year period. In the absence of head-to-head comparison trials between DOACs, relative risks were derived from a network meta-analysis. Clinical events considered include stroke/systemic embolism (SE) and major bleeding. Only direct health costs related to the management of clinical events and drug acquisition costs were considered. Clinical event management costs were derived from literature and from the Diagnosis Related Group (DRG) tariffs. Net annual treatment costs were calculated based on the daily dose reported in the Summary of Product Characteristics (SPCs) and the ex-factory price of each drug.RESULTS: Among DOACs, apixaban was associated with the highest net clinical benefit with 1,064 avoided events over 1 year, compared to warfarin (728 major bleeding events and 336 strokes/SE). Furthermore, apixaban is the most efficient DOAC, with a cost per avoided event equal to € 16,672 vs. warfarin (€ 24,120 for edoxaban 60 mg, € 36,777 for dabigatran 150 mg).CONCLUSION: Apixaban has the highest potential net clinical benefit among DOACs for patients with NVAF and the least incremental cost per avoided event for the Italian National Health Service.

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“…However, prospective data on this subject are not available, which is why the selection of the drug has to be based on the specific features of individual patients (in particular, age, renal function, liver function, pre-existing diseases, concomitant medication, compliance, etc.) [55,56]. A particularly critical question is the optimal time for the start of the treatment after stroke: If treatment is delayed, the patient is unprotected and exposed to a high risk of recurrence, but if the patient is anticoagulated too early, it could increase the risk of bleeding complications, or complicate acute management (e. g., hemicraniectomy in the case of a cerebral infarction).…”

Section: Antithrombotic Therapymentioning

confidence: 99%

Cardiac Arrhythmia following Stroke

Kallmünzer

Schwab

2017

Neurology International Open

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The autonomous innervation of the heart is based on a complex interaction of central and peripheral mechanisms in sympathetic and parasympathetic parts of the autonomic nervous system (▶Fig. 1). An extrinsic cardiac innervation is distinguished from an intrinsic one. Extrinsic systemTo put it simply, a center of the efferent parasympathetic innervation of the heart is found in the nucleus of the medulla oblongata, especially in the nucleus dorsalis [1]. The preganglionic fibers leave the central nervous system along with the vagus nerve and are connected to the second neuron in cardiac ganglion cells. Sympath etic fibers, on the other hand, originate from the nucleus intermediolateralis of the upper thoracic cord [2]. They reach the plexus cardiacus by means of the so-called "cardiac nerves" (usually 4 right-sided and 3 left-sided nervi cardiaci), after interposition in the border ganglia, especially in the ganglion stellatum. For the control of cardiac functions, the profound part of the plexus cardiacus is decisive; it extends between the tracheal bifurcation and the aortic arch, divides into a right and left half and in its further course follows the right or left coronary artery. The function of the efferent limb is modified by afferents from various organ systems, including the gastrointestinal tract or the carotissinus, by means of multisynaptic reflex arcs (e. g., baroreflex) [1]. In addition, in the blood circulating catecholamine, the release of which in the adrenal system is also subject to the autonomic system, mediates beta-adrenergic effects on the myocardium. It is postulated that dysbalances in the extrinsic system, in particular the pathological disinhibition of sympathetic activity, are relevant to the development of cardiac arrhythmias [1,[3][4][5]. For example, extensive brain stem damage can lead to suppression of central parasympathetic functions and overcoming of sympathetic tone [6], thus promoting the occurrence of cardiac arrhythmias. Conversely, blockade of the ganglion stellatum or renal sympathetic denervation should reduce the risk of ventricular arrhythmias in patients with prolonged-QT syndromes [7]. It is noteworthy in this context that extensive cardiac denervation, which may be present after orthotopic heart transplantation, is associated with a lower risk of supra ventricular rhythm disturbances, especially atrial fibrillation [8]. In these cases, the denervation should have protective effects and protect the myocardium from the autonomic imbalances of the extrinsic system before transmission. It should be noted, however, that organ donors are usually much younger and the vascular damage to the donor organs is often less pronounced, which significantly reduces the risk of atrial fibrillation independent of cardiac denervation [9].

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Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

Cited by 64 publications

References 76 publications

Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy

Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy

Estimating the cost-effectiveness of treatment for prevention of thromboembolic events in at-risk adults with non-valvular atrial fibrillation

Cardiac Arrhythmia following Stroke

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