Duthoit Guillaume, Silvain Johanne, Marijon Eloi, Ducrocq Grégory, Lepillier Antoine, Frere Corinne, Dimby Solohaja-Faniaha, Popovic Batric, Lellouche Nicolas, Martin-Toutain Isabelle, Spaulding Christian, Brochet Eric, Attias David, Mansourati Jacques, Lorgis Luc, Klug Didier, Zannad Noura, Hauguel-Moreau Marie, Braik Nassim, Deltour Sandrine, Ceccaldi Alexandre, Wang Hui, Hammoudi Nadjib, Brugier Delphine, Vicaut Eric, Juliard Jean-Michel, Montalescot Gilles
Sorbonne Université, ACTION Study Group (Allies in Cardiovascular Trials, Initiatives and Organized Networks), INSERM UMRS1166, ICAN, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France (G.D., J.S., N.B., A.C., N.H., D.B., G.M.).
European Georges Pompidou Hospital, APHP; Paris Descartes University, INSERM U 970, France (E.M., C.S.).
Circ Cardiovasc Interv. 2020 Jul;13(7):e008481. doi: 10.1161/CIRCINTERVENTIONS.119.008481. Epub 2020 Jul 17.
Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC.
ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R, n=37), rivaroxaban 15 mg (R, n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up.
The primary end point was reduced with R (179 pmol/L [interquartile range (IQR), 129-273], <0.0001) and R (163 pmol/L [IQR, 112-231], <0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R and R while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R to 274 ng/mL (IQR, 192-377) with R, <0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT.
Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.
经皮左心耳封堵术（LAAC）使房颤患者面临器械血栓形成的风险，这些患者通常有完全抗凝的禁忌证。因此，双重抗血小板治疗（DAPT）通常更受青睐。尚无随机研究评估LAAC术后使用非维生素K拮抗剂口服抗凝药的情况，我们决定评估LAAC术后低剂量利伐沙班的疗效和安全性。
ADRIFT（房颤患者左心耳封堵术后双重抗血小板治疗与利伐沙班的评估）是一项多中心IIb期研究，将105例LAAC成功后的患者随机分为利伐沙班10mg组（R，n = 37）、利伐沙班15mg组（R，n = 35）或阿司匹林75mg加氯吡格雷75mg的DAPT组（n = 33）。主要终点是在开始治疗10天后，服药2至4小时后测量的凝血酶生成（凝血酶原片段1 + 2）。在第10天和第3个月时还测量了凝血酶 - 抗凝血酶复合物、D - 二聚体、利伐沙班浓度。在3个月的随访中评估临床终点。
与DAPT组（322 pmol/L [四分位间距（IQR），218 - 528]）相比，R组（179 pmol/L [IQR，129 - 273]，<0.0001）和R组（163 pmol/L [IQR，112 - 231]，<0.0001）的主要终点降低。我们观察到R组和R组之间主要终点无显著降低，而利伐沙班浓度从R组的184 ng/mL（IQR，127 - 290）显著增加到R组的274 ng/mL（IQR，192 - 377），<0.0001。两种利伐沙班剂量的凝血酶 - 抗凝血酶复合物和D - 二聚体在数值上均低于DAPT组。这些结果在3个月时均得到证实。各组临床终点无差异。DAPT组有2例患者发生器械血栓形成。
LAAC术后接受低剂量利伐沙班治疗的患者凝血酶生成低于DAPT组，这支持了LAAC术后目前使用的抗血栓治疗方案的替代方案，值得在更大规模研究中进一步评估。注册信息：网址：https://www.clinicaltrials.gov。唯一标识符：NCT03273322。
