A Real­World Pharmacovigilance Study of FDA Adverse Event Reporting System (FAERS) for Mavacamten.

BACKGROUND: Mavacamten is a first-in-class cardiac myosin inhibitor approved by the US Food and Drug Administration (FDA) for symptomatic obstructive hypertrophic cardiomyopathy (HCM). This pharmacovigilance study aimed to assess mavacamten-related adverse drug reactions (ADRs) in the real world as reported in the FDA Adverse Event Reporting System (FAERS). METHODS: We conducted disproportionality analyses with four signal detection algorithms-reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and the multi-item gamma Poisson shrinker to identify mavacamten-related ADRs. RESULTS: Out of 4,500,131 reports from the FAERS database, 1004 mavacamten-related ADRs were identified from 1 January 2022 to 30 September 2023. A total of 26 significant disproportionality preferred terms (PTs) conforming to the four signal detection algorithms were noted. Some of the statistically significant cardiac ADRs at PT level include decreased ejection fraction (EF) [ROR 33.60 (95% confidence interval, CI 21.79-51.82), PRR 32.86 (χ2 615.96), information component (IC) 5.03, IC025 4.61, empirical Bayesian geometric mean (EBGM) 32.77, EBGM05 21.25], cardiac failure [ROR 9.39 (95% CI 6.49-13.60), PRR 9.13 (χ2 202.42), IC 3.19, IC025 2.83, EBGM 9.12, EBGM05 6.30], and atrial fibrillation [ROR 16.63 (95% CI 12.72-21.75), PRR 15.66 (χ2 769.93), IC 3.97, IC025 3.71, EBGM 15.64, EBGM05 11.96]. CONCLUSIONS: The results of our study were consistent with the safety data of clinical trials, including reduced ejection fraction, atrial fibrillation, dyspnea, and syncope. We also found potential new and unexpected ADR signals, such as urinary tract infection, gout, and peripheral edema.

Expanding Indications of Nonvitamin K Oral Anticoagulants Beyond Nonvalvular Atrial Fibrillation and Venous Thromboembolism: A Review of Emerging Clinical Evidence.

Direct oral anticoagulants (DOAC) have emerged as a new therapy for patients who need and can tolerate oral anticoagulation. DOACs were initially approved for nonvalvular atrial fibrillation (NVAF) and treatment for deep vein thrombosis (DVT) and pulmonary embolism (PE). Ease of administration, no requirement of bridging with other anticoagulants, and less frequent dosing have made DOACs preferable choice for anticoagulation. Studies are showing promising results regarding use of DOACs beyond the common indications. Studies have been done to show the potential benefit of DOACs in valvular atrial fibrillation, heart failure, acute coronary syndrome, stroke, and peripheral arterial disease. Data have shown safety as well as comparable bleeding incidences with DOACs compared to vitamin K antagonist anticoagulants. Naturally interest is growing to see the use of DOACs apart from the NVAF, DVT, or PE. Authors have highlighted various study results to show the potential beneficial role of DOACs in the above-mentioned situations.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in kidney transplant recipients: what is the evidence?

Several recent randomized controlled trials (RCTs) have demonstrated the wide clinical application of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in improving kidney and cardiovascular outcomes in patients with native kidney disease. In April 2021, Dapagliflozin became the first SGLT2 inhibitor to be approved by the Food and Drug Administration (FDA) for the treatment of chronic kidney disease (CKD) regardless of diabetic status. However, while these agents have drawn much acclaim for their cardiovascular and nephroprotective effects among patients with native kidney disease, little is known about the safety and efficacy of SGLT2i in the kidney transplant setting. Many of the mechanisms by which SGLT2i exert their benefit stand to prove equally as efficacious or more so among kidney transplant recipients as they have in patients with CKD. However, safety concerns have excluded transplant recipients from all large RCTs, and clinicians and patients alike are left to wonder if the benefits of these amazing drugs outweigh the risks. In this review, we will discuss the known mechanisms SGLT2i exploit to provide their beneficial effects, the potential benefits, and risks of these agents in the context of kidney transplantation, and finally, we will discuss current findings of the published literature for SGLT2i use in kidney transplant recipients and propose potential directions for future research.

Aspirin for Primary Prevention of Coronary Artery Disease.

Primary prevention of coronary artery disease (CAD) is an important means to reduce the burden of the disease. Aspirin has been widely prescribed over the last several decades as part of primary CAD prevention strategy. However, 3 recent hallmark trials - ARRIVE, ASCEND and ASPREE have raised serious questions about this common practice. Although, aspirin reduced incidence of non-fatal MI and stroke in these recent studies, bleeding risk was higher. In the present era, where regular exercise, healthy diet, smoking cessation, and statins are used to manage the risk factors of CAD, additional prescription of aspirin seems more harmful than beneficial. The guidelines of major societies such as European Society of Cardiology (ESC), American College of Cardiology (ACC), and American Heart Association (AHA) also reflect this shift. In this article, the authors aim to highlight the current evidence on aspirin use for primary prevention of CAD, in the context of evolving contrasting clinical trial data from the last 2 decades. We also highlight the pertinent sections of the most recent clinical guidelines of European Society of Cardiology, American College of Cardiology, and American Heart Association in this article.