The European Heart Rhythm Association Practical Compendium of Anti-arrhythmic Drugs (AADs) offers advice on these drugs, focusing on their clinical use and the global impact of cardiac arrhythmias. This document aims to provide practical instructions to clinicians in arrhythmia management through pharmacological strategies. The compendium highlights persistent challenges in arrhythmia treatment, including clinical constraints, procedural risks, and the complexity of certain arrhythmias. Notably, atrial fibrillation is highly prevalent, and the demand for invasive treatment often surpasses the capacity of existing healthcare systems. As a result, pharmacological management remains essential. This is particularly relevant for patients with cardiac implantable electronic devices or channelopathies, where ablation is often not a suitable option. Anti-arrhythmic drugs play a pivotal role in these scenarios. The compendium introduces the ABC framework for AAD therapy: A (Appropriate therapy), for patients in whom AADs are the best therapeutic option; B (Backup therapy), as adjunctive treatment to invasive procedures, such as catheter ablation; and C (Complementary therapy), in combination with other therapies. The document provides detailed insights into the mechanisms of action, efficacy, safety profiles, and drug interactions of each class of AADs. Additionally, the compendium covers practical considerations, including initiation, combination strategies, monitoring, follow-up, special populations, and adverse effect management, with an emphasis on pro-arrhythmia risk mitigation. It also explores the integration of AADs with other therapeutic modalities, promoting a synergistic approach to optimize patient outcomes. In summary, this compendium serves as an indispensable resource for clinicians, offering practical advice and evidence-based insights to navigate the complexities of arrhythmia management effectively.

There are sex-related differences (SRDs) in body composition, physiology, pharmacokinetics, efficacy, safety, and in dosage of some cardiovascular drugs. Thus, men and women may respond differently to certain drugs. However, information on SRDs in efficacy, safety, and dosage of cardiovascular drugs is scarce and their clinical relevance remains uncertain for two main reasons the traditional under-representation of women and drug efficacy and safety is not reported in a sex-disaggregated manner in randomized clinical trials (RCT). Thus, many RCTs were underpowered to analyse and detect SRDs, even if they do exist, and clinical practice guidelines (CPG) based on these RCTs recommend (with few exceptions) to treat women like men. Furthermore, women are less likely to receive CPG-recommended cardiovascular drugs (CPGRDs), present more adverse drug reactions, and may require lower doses of some drugs than men. In the era of 'precision medicine', this limited information should stimulate basic and clinical research to better understand the mechanisms underlying these SRDs in the efficacy and safety of CPGRDs because this represents the first step to develop a personalized pharmacotherapy. The aim of this narrative review is to analyse the reasons and consequences of the limited information on SRDs in efficacy, safety, and dosage of CPGRDs, to analyse whether the recommended doses are appropriate for women, to analyse the differences in the use of CPGRDs, and finally, to formulate recommendations to close our gaps in knowledge about SRDs and reverse the current situation to improve CVD prevention and treatment from a sex-specific perspective.

Antithrombotic therapy is essential after coronary artery bypass graft surgery to reduce ischaemic events and prevent graft occlusion. Although aspirin remains the most commonly used agent, in higher-risk patients, dual antiplatelet therapy or combining antiplatelet therapy with oral anticoagulation may be beneficial, but this increases bleeding risk. The choice of antithrombotic therapy should be tailored to each patient, based on their ischaemic and bleeding risks, and regularly reassessed. Here, the scientific evidence underlying the key aspects of the choice of antithrombotic therapy after coronary artery bypass grafting is reviewed. Consensus statements for best clinical practice are provided and areas requiring further research are highlighted.

Despite substantial advances in cardiovascular pharmacotherapy and devices in recent years, prevention and treatment of many cardiovascular diseases (CVDs) remain limited, thus reflecting the need for more effective and safer pharmacological strategies. In this review, we summarize the most relevant studies in cardiovascular pharmacotherapy in 2024, including the approval of first-in-class drugs for the treatment of resistant hypertension and pulmonary arterial hypertension, label expansions for bempedoic acid and semaglutide, and the results of major randomized clinical trials (RCTs) that have met the pre-specified primary endpoints, thereby filling some gaps in knowledge and opening new perspectives in the management of CVD, and those RCTs whose results did not confirm the proposed research hypotheses. We also include a section on drug safety, where we describe the newest data on adverse reactions and drug-drug interactions that may complicate treatment and/or reduce drug adherence with the consequent decrease in drug effectiveness. Finally, we present the most important ongoing phase 2 and phase 3 clinical trials assessing the efficacy and safety of cardiovascular drugs for the prevention and treatment of CVD.

Dapagliflozin and empagliflozin exert many cardiovascular protective actions in heart failure (HF) patients. HF-induced electrical remodelling decreases the expression of Nav1.5 channels (encoded by SCN5A) that generate the cardiac Na+ current (INa) impairing excitability and promoting arrhythmias. We aimed to mechanistically decipher the peak INa increase produced by dapagliflozin and empagliflozin in healthy and HF cardiomyocytes. We recorded macroscopic and single-channel currents and action potentials (AP) using the patch-clamp technique and generated a mouse model of HF with reduced ejection fraction by transverse aortic constriction (TAC). Single-channel recordings showed that dapagliflozin and empagliflozin (1 μM) increased the open probability (Po) of Nav1.5 channels by augmenting channel re-openings and the number of traces with openings and by doubling the open time constant, respectively. Both drugs increased SCN5A mRNA levels and the membrane expression of Nav1.5 channels. Empagliflozin also enhanced the cytoplasmic mobility of Nav1.5 channels. Molecular modelling and site-directed mutagenesis analysis demonstrated that both drugs bind to a previously unknown site at the Nav1.5 DIII-DIV fenestration. Dapagliflozin and empagliflozin hyperpolarized the resting membrane potential and increased the action potential amplitude in human cardiomyocytes derived from induced pluripotent stem cells. Importantly, in TAC cardiomyocytes dapagliflozin and empagliflozin restored the HF-reduced peak INa to control levels. Dapagliflozin and empagliflozin bind to a novel site within cardiac Nav1.5 increasing INa by augmenting the Po and the membrane expression of the channels. We hypothesized that this unique effects could be of interest for the treatment of arrhythmias associated with decreased Nav1.5 channel expression.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased morbidity and mortality. There is clinical evidence that an increasing number of cardiovascular and non-cardiovascular drugs, mainly anticancer drugs, can induce AF either in patients with or without pre-existing cardiac disorders, but drug-induced AF (DIAF) has not received the attention that it might deserve. In many cases DIAF is asymptomatic and paroxysmal and patients recover sinus rhythm spontaneously, but sometimes, DIAF persists, and it is necessary to perform a cardioversion. Furthermore, DIAF is not mentioned in clinical guidelines on the treatment of AF. The risk of DIAF increases in elderly and in patients treated with polypharmacy and with risk factors and comorbidities that commonly coexist with AF. This is the case of cancer patients. Under these circumstances ascribing causality of DIAF to a given drug often represents a clinical challenge. We review the incidence, the pathophysiological mechanisms, risk factors, clinical relevance, and treatment of DIAF. Because of the limited information presently available, further research is needed to obtain a deeper insight into DIAF. Meanwhile, it is important that clinicians are aware of the problem that DIAF represents, recognize which drugs may cause DIAF, and consider the possibility that a drug may be responsible for a new-onset AF episode.

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs.

Cardioembolic stroke is a serious complication in atrial fibrillation ( AF) , and stroke prevention by oral anti-coagulants ( OACs) is the cornerstone in the management of AF.Current guidelines recommend OACs for high risk AF patients, including those with aged ≥75 years.Data about the use of OACs among frail very elderly ( ≥85 years) with AF are limited because they were underrepresented in clinical trials, but considering the aging of the population, evidence to support a beneficial anticoagulation regimen in this population is needed.Among patients with AF ≥90 years of age, warfarin was associated with a lower risk of ischaemic stroke and positive net clinical benefit. 1 However, OACs are underused in elderly patients with AF, mainly because of safety concerns related to fall risk, drug interactions, low adherence, and perceived bleeding risk. 2 A network meta-analyses, using individual patient-level data from the randomized trials of non-vitamin K oral anti-coagulants ( NOACs) , showed standard-dose NOACs resulted in significant reductions in the risk of stroke/systemic embolism, intracranial bleeding, and all-cause death compared with vitamin K antagonists ( VKAs) , regardless of patient age. 3 Real world data support the better net clinical benefits of NOACs in elderly patients with AF. 1 , 4 These advantages are primarily observed in OAC-naïve patients.The FRAIL-AF trial was a pragmatic open-label randomized trial in frail elderly AF patients ( mean age, 83 years; GFI score ≥ 3; mean CHADS2-VASc score, 4) in the Netherlands.The trial was conducted with well-established infrastructure for VKA treatment, and the time in therapeutic range ( TTR) for the oldest patient groups ranged from 65 to 74% in clinical practice.This trial demonstrated that switching from VKAs to NOACs in patients who were stable on INR-guided VKA treatment was associated with more bleeding complications without an associated reduction in thromboembolic complications. 5This association was mainly attributed to an increase

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimising antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.

INTRODUCTION:Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches. AREAS COVERED:This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF. EXPERT OPINION:The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

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Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines. The AF-CARE framework is introduced, a structural approach that aims to improve patient care and outcomes, comprising of four pillars: [C] Comorbidity and risk factor management, [A] Avoid stroke and thromboembolism, [R] Reduce symptoms by rate and rhythm control, and [E] Evaluation and dynamic reassessment. Additionally, graphical patient pathways are provided to enhance clinical application. A significant shift is the new emphasis on comorbidity and risk factor control to reduce AF recurrence and progression. Individualized assessment of risk is suggested to guide the initiation of oral anticoagulation to prevent thromboembolism. New guidance is provided for anticoagulation in patients with trigger-induced and device-detected sub-clinical AF, ischaemic stroke despite anticoagulation, and the indications for percutaneous/surgical left atrial appendage exclusion. AF ablation is a first-line rhythm control option for suitable patients with paroxysmal AF, and in specific patients, rhythm control can improve prognosis. The AF duration threshold for early cardioversion was reduced from 48 to 24 h, and a wait-and-see approach for spontaneous conversion is advised to promote patient safety. Lastly, strong emphasis is given to optimize the implementation of AF guidelines in daily practice using a patient-centred, multidisciplinary and shared-care approach, with the simultaneous launch of a patient version of the guideline.