Janssen Pharmaceuticals, Inc., Janssen Scientific Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
Janssen Pharmaceuticals, Inc., Janssen Medical Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
Am J Cardiovasc Drugs. 2021 May;21(3):283-297. doi: 10.1007/s40256-020-00434-w.
Cardiovascular disease (CVD) remains the leading cause of death in the USA. Several risk factors have been identified, and obesity has become one of prominent concern. Excessive weight is considered a risk factor for CVD based on evidence linking it to a hypercoagulable state. Considering the prevalence of CVD and obesity in the USA, along with the increased risk for thrombus-related events, anticoagulation plays a significant role in prevention and treatment. Direct oral anticoagulants have taken the place of many traditional anticoagulants. Considering the recently approved indications and continued postmarketing studies conducted with rivaroxaban, this updated review provides data on the overall impact of obesity on this compound. This includes data obtained from both healthy obese volunteers and obese patients with various CVD conditions enrolled in rivaroxaban clinical trials, along with data obtained from postmarketing real-world evidence studies. Assessment of the clinical pharmacology and population pharmacokinetics in obese individuals revealed no clinically relevant effects of increased weight. Additionally, subgroup analyses from each of the pivotal phase III trials supporting the current approved labeling also demonstrated consistent efficacy and safety results in obese patients. Lastly, these findings are further supported by several recent real-world evidence studies assessing the continued effectiveness and safety of rivaroxaban. In conclusion, rivaroxaban's overall pharmacological and clinical profile remained consistent in obese adults when assessed in both drug development and postmarketing studies, supporting the premise that higher weight does not necessitate adjustment in either dose strength or regimen.
心血管疾病(CVD)仍然是美国的主要死因。已经确定了几个风险因素,肥胖已成为一个突出的关注点。根据将其与高凝状态联系起来的证据,超重被认为是 CVD 的一个风险因素。考虑到 CVD 和肥胖在美国的流行,以及与血栓相关事件的风险增加,抗凝在预防和治疗中起着重要作用。直接口服抗凝剂已经取代了许多传统的抗凝剂。考虑到利伐沙班最近批准的适应症和持续进行的上市后研究,本更新综述提供了关于肥胖对这种化合物的总体影响的数据。这包括从参加利伐沙班临床试验的健康肥胖志愿者和患有各种 CVD 疾病的肥胖患者中获得的数据,以及从上市后真实世界证据研究中获得的数据。对肥胖个体的临床药理学和群体药代动力学评估显示,体重增加没有临床相关影响。此外,支持当前批准标签的每项关键性 III 期试验的亚组分析也表明肥胖患者的疗效和安全性结果一致。最后,这些发现还得到了几项最近评估利伐沙班持续有效性和安全性的真实世界证据研究的进一步支持。总之,在药物开发和上市后研究中,评估肥胖成年人时,利伐沙班的整体药理学和临床特征保持一致,这支持了这样一种观点,即体重增加不需要调整剂量强度或方案。