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Bisphosphonates and atrial fibrillation: revisiting the controversy.

08:00 EDT 24th March 2020 | BioPortfolio

Summary of "Bisphosphonates and atrial fibrillation: revisiting the controversy."

Bisphosphonates (BPs) are widely prescribed drugs used to treat osteoporosis, commonly arising in postmenopausal women and in chronic glucocorticoid use. Their mechanism of action is through inhibiting osteoclast-induced bone remodeling, and they also possess calcium sequestering properties. Common side effects involve the gastrointestinal system and rare but serious side effects, including osteonecrosis of the jaw. However, a link between BPs and atrial fibrillation (AF) has been proposed, with early clinical trials, such as the Fracture Intervention Trial and the HORIZON Pivotal Fracture Trial, reporting that BPs are associated with increased risk of AF. Nevertheless, subsequent studies have reported contrasting results, ranging from no effect of BPs to antiarrhythmic effects of BPs. Preclinical and electrophysiological studies on any proarrhythmic effect of BPs are limited in scope and number, but suggest possible mechanisms that include antiangionesis-related myocardial remodeling, calcium handling abnormalities, and inflammatory changes. Contrastingly, some studies indicate that BPs are antiarrhythmic by inhibiting fibrotic myocardial remodeling. In order to continue established clinical prescribing of BPs within absolute margins of safety, it will be necessary to systematically rule in/rule out these mechanisms. Thus, we discuss these studies and examine in detail the potential mechanistic links, with the aim of suggesting further avenues for research.

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This article was published in the following journal.

Name: Annals of the New York Academy of Sciences
ISSN: 1749-6632
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Medical and Biotech [MESH] Definitions

Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).

Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)

Impaired or delayed impulse conduction between the right and left HEART ATRIA. Advanced interatrial blocks are often associated with arrhythmias (e.g., ATRIAL FLUTTER; and ATRIAL FIBRILLATION), direct conduction block via the Bachmann's bundle and concomitant left atrial enlargement. Syndrome of advanced interatrial block associated with SUPRAVENTRICULAR TACHYCARDIA is referred to as Bayes syndrome.

The process of bargaining in order to arrive at an agreement or compromise on a matter of importance to the parties involved. It also applies to the hearing and determination of a case by a third party chosen by the parties in controversy, as well as the interposing of a third party to reconcile the parties in controversy.

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