Verdoia M, Suryapranata H, Damen S, Camaro C, Benit E, Barbieri L, Rasoul S, Liew H B, Polad J, Ahmad W A W, Zambahari R, Lalmand J, van der Schaaf R J, Koh T H, Timmermans P, Dilling-Boer D, Veenstra L F, Van't Hof A W J, Lee S W L, Roolvink V, Ligtenberg E, Postma S, Kolkman E J J, Brouwer M A, Kedhi E, De Luca G
AOU Maggiore Della Carità, Eastern Piedmont University, Novara, Italy.
Radboud University Medical Center, Nijmegen, The Netherlands.
J Thromb Thrombolysis. 2021 Oct;52(3):797-807. doi: 10.1007/s11239-021-02439-x. Epub 2021 Apr 13.
Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study.
REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months.
From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender.
The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.
血栓形成和出血风险方面的性别差异被认为会影响抗血栓治疗对急性冠状动脉综合征（ACS）患者的益处，在接受药物洗脱支架（DES）经皮冠状动脉介入治疗的患者中尤为明显。性别对ACS患者双联抗血小板治疗（DAPT）最佳疗程的影响仍未得到探索，因此，本亚组研究旨在探讨这一问题。
REDUCE是一项前瞻性、多中心、由研究者发起的随机研究，基于非劣效性设计，旨在纳入1500例接受COMBO双支架治疗后的ACS患者。患者以1:1的比例随机分为接受3个月或12个月DAPT治疗。主要研究终点是12个月时全因死亡率、心肌梗死、明确/可能的支架血栓形成（ST）、中风、靶血管血运重建（TVR）和出血（BARC II、III、V型）的复合终点。次要终点是24个月内心血管死亡率以及主要终点的各个组成部分。
2014年6月至2016年5月，共有300名女性和1196名男性纳入研究。其中，43.7%的女性和51.9%的男性被分配接受3个月DAPT治疗。两组的基线特征基本匹配，但女性中TIMI血流<3级的发生率较低（p = 0.04）、收缩压较低（p = 0.05）以及螺内酯使用率较低（p = 0.006），而接受短期DAPT治疗的男性年龄较大（p = 0.05）。在平均随访525（±198）天时，无论DAPT疗程长短，女性[6.9%对5.9%，HR（95%CI）= 1.19（0.48 - 2.9），p = 0.71]和男性[8.2%对9%，HR（95%CI）= 0.92（0.63 - 1.35），p = 0.67；p INT = 0.20]的主要终点均无差异。在校正基线差异后结果得到证实[女性：校正后HR（95%CI）= 1.12（0.45 - 2.78），p = 0.81；男性：校正后HR（95%CI）= 0.90（0.61 - 1.32），p = 0.60]。两种DAPT策略的生存、血栓形成（心肌梗死、支架血栓形成、TVR、中风）和出血事件发生率相当，且不受性别的影响。
本研究表明，在REDUCE试验中随机分组的ACS患者中，在2年随访时，3个月DAPT策略与标准的12个月DAPT策略相比，在男性和女性中均能提供相当的结果。
