Washam Jeffrey B, Hellkamp Anne S, Lokhnygina Yuliya, Piccini Jonathan P, Berkowitz Scott D, Nessel Christopher C, Becker Richard C, Breithardt Günter, Fox Keith A A, Halperin Jonathan L, Hankey Graeme J, Mahaffey Kenneth W, Singer Daniel E, Patel Manesh R
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Am J Cardiol. 2017 Aug 15;120(4):588-594. doi: 10.1016/j.amjcard.2017.05.026. Epub 2017 May 29.
Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF.
非二氢吡啶类钙通道阻滞剂（非 DHP CCBs）具有联合的 P-糖蛋白抑制作用和中等程度的 CYP3A4 抑制作用，这可能导致作为这些代谢途径底物的药物（如利伐沙班）的暴露增加。我们在房颤患者中评估了非 DHP CCBs 的使用情况及结局，这些患者来自利伐沙班每日一次口服直接因子 Xa 抑制与维生素 K 拮抗剂预防房颤患者卒中及栓塞试验（ROCKET AF）。我们评估了接受非 DHP CCBs 的患者的临床结局，以及与华法林相比其对利伐沙班疗效和安全性的影响。根据非 DHP CCBs 的使用情况，比较了卒中或非中枢神经系统（CNS）系统性栓塞（SE）、主要或非主要临床相关（NMCR）出血、全因死亡和大出血情况。随机分组时，1308 例患者（9.2%）正在服用非 DHP CCBs。他们更可能为女性，患有糖尿病和慢性阻塞性肺疾病（COPD），而发生心力衰竭的可能性较小，且平均 CHADS 评分较低（3.3 对 3.5）。使用非 DHP CCBs 与卒中/非 CNS SE 风险增加（p = 0.11）或 NMCR 或大出血的复合结局风险增加无关（p = 0.087）。使用非 DHP CCBs 与大出血风险增加（调整后风险比 1.50，95%可信区间 1.11 至 2.04）和颅内出血风险增加（调整后风险比 2.84，95%可信区间 1.53 至 5.29）相关。在使用非 DHP CCBs 的情况下，利伐沙班与华法林在主要疗效（卒中或非 CNS SE；调整后交互 p 值 =
0.38）或安全性结局（NMCR 或大出血；调整后交互 p 值 = 0.14）方面未观察到显著差异。总之，尽管非 DHP CCBs 的总体使用与大出血和颅内出血风险增加相关，但在 ROCKET AF 试验中，与华法林相比，其使用并未导致利伐沙班的安全性或疗效发生显著变化。
