Bruton tyrosine kinase (BTK) plays a pivotal role in B-cell receptor signaling, making it a key therapeutic target in hematologic malignancies. Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment landscape, improving survival outcomes in conditions such as chronic lymphocytic leukemia and mantle cell lymphoma. However, despite their clinical efficacy, BTKIs—particularly first-generation agents such as ibrutinib—are associated with significant cardiovascular toxicity, including atrial fibrillation, hypertension, bleeding, and, in rare cases, ventricular arrhythmias and heart failure. This narrative review explores the evolving landscape of BTKI-related cardiovascular toxicity, from first-generation drugs to next-generation agents that have improved safety profiles. We summarize current evidence on the incidence, mechanisms, and risk factors of BTKI-induced cardiovascular events and highlight potential predictive tools and mitigation strategies. Given the increasing use of these agents, a comprehensive understanding of their cardiovascular impact is essential for optimizing treatment selection and patient outcomes. Future research should focus on refining risk stratification models and developing cardioprotective strategies to ensure the long-term safety of BTKI therapy.

BackgroundOral anticoagulants (OACs) are recommended for stroke reduction in non-valvular atrial fibrillation (NVAF). OAC use has been studied in Medicare populations, but data for younger, commercially insured populations are limited.ObjectiveThis retrospective study aimed to describe the geographic variation of OAC use among commercially insured patients with NVAF at high risk of stroke (CHA2DS2-VASc score ≥ 2) in the USA.MethodsGeographic variation was assessed by 3-digit zip code and race among patients identified from the Komodo Health commercial database with a diagnosis of NVAF between January 1, 2016, and August 31, 2021. Continuous health plan enrollment for ≥ 12 months before and 12 months after the NVAF diagnosis was required.ResultsA total of 619,111 patients with NVAF at high risk for stroke were identified, of whom approximately 50% were not treated with OACs. Of the half who received OACs, almost 85% received direct OACs (DOACs) and 15% received warfarin therapy. Overall, the highest untreated rates were observed in the South and West US regions, followed by the Midwest, then the Northeast. The highest DOAC treatment rates were in the Northeast for White patients and in the North and South for Black patients. The highest warfarin treatment rates were in the upper Midwest for White patients and the Midwest for Black patients.ConclusionsThis study may help guide the identification of areas to target interventions to improve treatment rates and confirm prior findings of geographic and racial variations of OAC use in NVAF.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-025-00728-x.

BackgroundPatients with adult congenital heart disease (CHD) have various indications for anticoagulation (e.g., presence of Fontan circuit, atrial fibrillation due to surgical scar). Guidelines recommend vitamin K antagonists (VKA) for thromboprophylaxis in adult CHD, as trial data comparing safety/efficacy of direct oral anticoagulants (DOAC) to VKA are not available in this population.MethodsPubMed/MEDLINE, Embase, Web of Science, and Google Scholar were searched for trials comparing DOAC with VKA in patients with ACHD. Outcomes of interest were efficacy endpoints (thromboembolic complications) and safety endpoints (bleeding complications). Results were meta-analyzed and sensitivity analyses were performed.ResultsA total of 4 retrospective studies comprising 6004 patients (2566 DOAC, 3438 VKA) were analyzed. Compared with VKA, DOAC did not cause a statistically significant difference in incidence of thromboembolism (risk ratio, RR, 0.76; 95% confidence intervals, CI, 0.28, 2.07); composite bleeding (RR 1.02, 95% CI 0.71, 1.47); major bleeding (RR 1.05, 95% CI 0.92, 1.21); minor bleeding (RR 1.12, 95% CI 0.51, 2.44); or intracranial bleeding (RR 0.86, 95% CI 0.50, 1.46). Numerically, the DOAC arm had fewer thromboembolisms/intracranial bleeds but more major/composite bleeds. However, upon removal of the largest study, the DOAC arm had fewer major/composite bleeds.ConclusionsDOAC did not confer a significant increase in either thromboembolic or bleeding risk as compared with VKA. Sensitivity analysis showed notable heterogeneity among studies. Large-scale trials comparing DOAC with VKA in patients with adult CHD are needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-025-00720-5.

Finerenone is a novel nonsteroidal mineralocorticoid receptor (MR) antagonist (MRA) with unique pharmacological properties that offer potent and selective blockade of the MR with a more favorable side effect profile than spironolactone and eplerenone. In a large phase III clinical trial involving 13,026 patients with type 2 diabetes mellitus and a broad spectrum of chronic kidney disease, finerenone provoked a substantial placebo-subtracted reduction in the risk of hospitalization for heart failure (HF). These preliminary clinical trial data, along with the ongoing uncertainty about the safety and efficacy of MR antagonism in patients with HF and higher levels of ejection fraction have provided the rationale for the design of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure) trial. In this multicenter, double-blind, randomized, phase III trial involving 6001 patients with HF and mildly reduced or preserved ejection fraction, finerenone was superior to placebo in improving the primary composite outcome of total (first and recurrent) worsening HF events and death from cardiovascular causes. This benefit was similar in magnitude in patients receiving and in patients not receiving background treatment with a sodium-glucose co-transporter type 2 inhibitor, suggesting a potential additive benefit with combination therapy. We explore the emerging role of the nonsteroidal MRA finerenone as a new therapeutic opportunity to improve the risk of adverse cardiovascular outcomes in patients with HF and mildly reduced or preserved ejection fraction. We discuss preliminary clinical trial data and provide a critical evaluation of the main results of the FINEARTS-HF trial.

Around one-quarter of all patients undergoing cardiac procedures, particularly those on cardiopulmonary bypass, develop cardiac surgery-associated acute kidney injury (CSA-AKI). This complication increases the risk of several serious morbidities and of mortality, representing a significant burden for both patients and the healthcare system. Patients with diminished kidney function before surgery, such as those with chronic kidney disease, are at heightened risk of developing CSA-AKI and have poorer outcomes than patients without preexisting kidney injury who develop CSA-AKI. Several mechanisms are involved in the development of CSA-AKI; injury is primarily thought to result from an amplification loop of inflammation and cell death, with complement and immune system activation, cardiopulmonary bypass, and ischemia-reperfusion injury all contributing to pathogenesis. At present there are no effective, targeted pharmacological therapies for the prevention or treatment of CSA-AKI, although several preclinical trials have shown promise, and clinical trials are under way. Progress in the understanding of the complex pathophysiology of CSA-AKI is needed to improve the development of successful strategies for its prevention, management, and treatment. In this review, we outline our current understanding of CSA-AKI development and management strategies and discuss potential future therapeutic targets under investigation.

PurposeApixaban, a direct oral anticoagulant is administered for stroke prevention in atrial fibrillation patients. Dosing adjustment is guided by renal function, age, and body weight. However, no data exist on its pharmacokinetics in patients with a body mass index (BMI) ≥ 35 kg/m2. The aim was to investigate the effects of BMI ≥ 35 kg/m2 on trough plasma concentrations of apixaban in patients with atrial fibrillation.MethodsThis prospective study compared steady-state trough concentrations of apixaban in patients with a BMI ≥ 35 kg/m2 and patients with a BMI < 35 kg/m2.ResultsSixty patients were included. In patients receiving 5 mg apixaban twice daily, the median trough plasma concentration was 29% lower in patients with a BMI ≥ 35 kg/m2 than in those with a BMI < 35 kg/m2 (148.9 ng/ml, interquartile range [IQR] 94.5–205.6, compared to 209.1 ng/ml, IQR 167–266.8 ng/ml, respectively; P = 0.044). However, median trough concentrations fell within the manufacturer’s predicted range for effective steady-state apixaban exposure. A similar trend was observed with 2.5 mg apixaban twice daily, although statistical significance was not reached. Multivariate analysis revealed no correlation between BMI values and trough concentrations.ConclusionBMI ≥ 35 kg/m2 patients exhibited lower apixaban trough concentrations, while remaining within the manufacturer’s established range for effective steady-state apixaban, suggesting that dose adjustment is unnecessary for this specific patient group.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues. It has multiple features that may contribute to its cardiovascular protection. Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiological barriers. Additionally, this indoleamine also serves as a safe exogenous therapeutic agent. Increasing evidence has demonstrated the beneficial effects of melatonin in preventing and improving cardiovascular risk factors. Exogenous administration of melatonin, as a result of its antioxidant and anti-inflammatory properties, has been reported to decrease blood pressure, protect against atherosclerosis, attenuate molecular and cellular damage resulting from cardiac ischemia/reperfusion, and improve the prognosis of myocardial infarction and heart failure. This review aims to summarize the beneficial effects of melatonin against these conditions, the possible protective mechanisms of melatonin, and its potential clinical applicability in CVDs.

The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF >40%). Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

This article reviews available evidence regarding hypertension management in the Asia-Pacific region, focussing on five research questions that deal with specific aspects: blood pressure (BP) control, guideline recommendations, role of renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice, pharmacological management and real-world adherence to guideline recommendations. A PubMed search identified 2537 articles, of which 94 were considered relevant. Compared with Europeans, Asians have higher systolic/diastolic/mean arterial BP, with a stronger association between BP and stroke. Calcium channel blockers are the most-commonly prescribed monotherapy in Asia, with significant variability between countries in the rates of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and single-pill combination (SPC) use. In clinical practice, ARBs are used more commonly than ACEis, despite the absence of recommendation from guidelines and clinical evidence supporting the use of one class of drug over the other. Ideally, antihypertensive treatment should be tailored to the individual patient, but currently there are limited data on the characteristics of hypertension in Asia-Pacific individuals. Large outcome studies assessing RAAS inhibitor efficacy and safety in multi-national Asian populations are lacking. Among treated patients, BP control rates were ~ 35 to 40%; BP control in Asia-Pacific is suboptimal, and disproportionately so compared with Western nations. Strategies to improve the management of hypertension include wider access/availability of affordable treatments, particularly SPCs (which improve adherence), effective public health screening programs targeting patients to drive health-seeking behaviours, an increase in physician/patient awareness and early implementation of lifestyle changes. A unified Asia-Pacific guideline on hypertension management with pragmatic recommendations, particularly in resource-limited settings, is essential.

ObjectiveTo assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.MethodsIn this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration–time data using noncompartmental methods.ResultsOf the 45 participants randomized, 37 completed the study. When activated charcoal was administered 2 h after mavacamten dosing, mavacamten absorption and exposure were reduced compared with when mavacamten was administered alone: the area under the concentration–time curve from 0 to 72 h (AUC0–72) and area under the concentration–time curve from time 0 extrapolated to infinity (AUCINF) were reduced by 14% and 34%, respectively. The maximum plasma concentration (Cmax) was also slightly lower when activated charcoal was administered 2 h after mavacamten dosing than with mavacamten alone. Pharmacokinetic profiles were similar for mavacamten alone and mavacamten plus activated charcoal administered 6 h after mavacamten dosing.ConclusionsActivated charcoal was successful in reducing mavacamten absorption and exposure when administered as soon as possible after identification of a need for adsorption (2 h after mavacamten dosing). No change in exposure was observed when activated charcoal was administered 6 h after mavacamten dosing.Clinical Trial RegistrationNCT05320094Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-024-00659-z.