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Accepted: 11 September 2022 / Published online: 18 October 2022
© The Author(s) 2022
Abstract
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting approximately 335 million patients worldwide. Comprehensive pharmacological treatment of AF includes medications for rate or rhythm control and anticoagulants to reduce the risk of thromboembolism; yet, these agents have significant limitations. Oral anti-arrhythmic agents have a slow onset of action, and rapid onset formulations require hospitalization for intravenous therapy. Orally administered drugs also require high doses to attain therapeutic levels, and thus dose-related severe adverse effects are often unavoidable. Given the therapeutic benefits of inhaled drug delivery, including rapid onset of action and very low doses to achieve therapeutic efficacy, this review will discuss the benefits of novel pulmonary delivery of drugs for the management of AF.
1Introduction
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and is associated with increased mortality and decreased quality of life through its complications such as heart failure and stroke [1, 2]. It has been reported that more than 335 million people are suffering from AF globally [3]. More importantly, the incidence is rapidly rising owing to changing lifestyles and an increasingly aging global population. AF results from abnormal electrical impulses in the atria, and the passing of these irregular signals to the ventricles results in a rapid and abnormal heartbeat. While the exact cause of AF is uncertain, common risk factors include coronary artery disease, hypertension, cardiomyopathies and valvular heart disease, along with other comorbidities that impact the heart. Contemporary drug management of AF using currently available oral anti-arrhythmic drugs has a relatively slow onset of action, which reduces their effectiveness for management of acute episodes of rapid AF, while rapid-onset intravenous formulations often require hospitalization and intravenous cannulation for drug administration and monitoring of adverse effects. AF can lead to thromboembolic phenomena such as stroke or myocardial infarction [4]. Oral vitamin K antagonist (warfarin) and novel nonvitamin K antagonist oral anticoagulant (NOAC) drugs substantially reduce the risk of thrombus formation and clinical sequalae such as stroke [5-7]. The use of these drugs in clinical practice remains challenging as long-term use of oral anticoagulants has the potential to cause dose-related gastrointestinal bleeding and fatal intracranial hemorrhage. To overcome these limitations...