2019年9月1日的《柳叶刀》在线发表了美国布里格姆妇女医院和哈佛医学院Deepak L Bhatt团队的最新成果。他们的研究探讨了替卡格雷治疗有经皮冠状动脉介入治疗（PCI）史的糖尿病和稳定冠状动脉疾病患者的疗效。

替卡格雷干预糖尿病患者的健康结局（THEMIS）项目在42个国家的1315个地点进行，这是一项临床3期、随机、双盲、安慰剂对照试验。受试者的年龄超过50岁，患2型糖尿病，至少进行6个月的抗高血糖药物治疗，且伴有稳定的冠状动脉疾病。受试者既往有PCI史或行冠状动脉旁路移植术，或有记录显示至少一根冠状动脉血管造影狭窄超过50%。

2014年2月17日至2016年5月24日，11154名既往有PCI史的患者参加了THEMIS-PCI试验，按1：1随机分配到替卡格雷组（5558名）或安慰剂组（5596名）。中位随访3.3年后，替卡格雷组中有404例（7.3%）发生心血管死亡、心肌梗死或中风，显著低于安慰剂组（480例，8.6%），风险比为0.85。既往无PCI史的患者中未观察到同样结果。

两组患者中心血管死亡率和全因死亡率相差不大。替卡格雷组中有111例（2.0%）出现TIMI大出血，显著高于安慰剂组（62例，1.1%）。两组致命性出血的发生率均为0.1%，颅内出血的发生率均为0.6%。替卡格雷改善了净临床获益率，无论最近一次PCI治疗的时间长短，患者均临床获益。

在糖尿病、稳定冠脉疾病和既往有PCI史的患者中，阿司匹林联合替卡格雷可减少心血管死亡、心肌梗死和中风，但增加了大出血的风险。因此，对于糖尿病、有PCI史、耐受抗血小板治疗、缺血性风险高、出血风险低的患者应考虑长期服用替卡格雷和阿司匹林。

据悉，既往有PCI史的稳定冠心病和糖尿病患者，特别是支架置入的患者，发生缺血性事件的风险较高。这些病人通常用阿司匹林治疗。

附：英文原文

Title: Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author: Deepak L Bhatt;Philippe Gabriel Steg;Shamir R Mehta;Lawrence A Leiter;Tabassome Simon;Kim Fox;Claes Held;Marielle Andersson;Anders Himmelmann;Wilhelm Ridderstrale;Jersey Chen;Yang Song;Rafael Diaz;Shinya Goto;Stefan K James;Kausik K Ray;Alexander N Parkhomenko;Mikhail N Kosiborod;Darren K McGuire;Prof Robert A Harrington;on behalf of the THEMIS Steering Committee and Investigators

Issue&Volume: 1 September 2019

Summary

Background

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.

Methods

The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).

Findings

Between Feb 17, 2014, and May 24, 2016, 11?154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI.

Interpretation

In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.: 

DOI: https://doi.org/10.1016/S0140-6736(19)31887-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31887-2/fulltext