Background Patients who have had an acute coronary syndrome (ACS) event have an increased risk for depression.
Purpose To evaluate the diagnostic accuracy of depression screening instruments and to compare safety and effectiveness of depression treatments in adults within 3 months of an ACS event.
Data Sources MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews from January 2003 to August 2017, and a manual search of citations from key primary and review articles.
Study Selection English-language studies of post-ACS patients that evaluated the diagnostic accuracy of depression screening tools or compared the safety and effectiveness of a broad range of pharmacologic and nonpharmacologic depression treatments.
Data Extraction 2 investigators independently screened each article for inclusion; abstracted the data; and rated the quality, applicability, and strength of evidence.
Data Synthesis Evidence from 6 of the 10 included studies showed that a range of depression screening instruments produces acceptable levels of diagnostic sensitivity, specificity, and negative predictive values (70% to 100%) but low positive predictive values (below 50%). The Beck Depression Inventory-II was the most studied tool. A large study found that a combination of cognitive behavioral therapy (CBT) and antidepressant medication improved depression symptoms, mental health-related function, and overall life satisfaction more than usual care.
Limitation Few studies, no evaluation of the influence of screening on clinical outcomes, and no studies addressing several clinical interventions of interest.
Conclusion Depression screening instruments produce diagnostic accuracy metrics that are similar in post-ACS patients and other clinical populations. Depression interventions have an uncertain effect on cardiovascular outcomes, but CBT combined with antidepressant medication produces modest improvement in psychosocial outcomes.
Primary Funding Source Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).
在接受经皮冠状动脉介入治疗（PCI）和支架置入的急性冠状动脉综合征（ACS）患者中，双重抗血小板治疗的最佳治疗时间尚不清楚。 在SMART-DATE试验中，超过2700名此类患者被随机分配到使用阿司匹林和P2Y12抑制剂的双重抗血小板治疗6个月或≥12个月。 虽然MI治疗的次要终点更常发生，但全因死亡，中风和心肌梗塞（MI）的主要复合终点事件发生率在两组中均相似。 基于所有现有证据，我们治疗的ACS患者接受PCI最短持续12个月，除非出血风险非常高。
BACKGROUND Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population.
METHODS We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation,to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453.
FINDINGS Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%]patients vs 39 [2·9%]; hazard ratio [HR]0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%]patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%]patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis.
INTERPRETATION The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.
FUNDING Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.
心肌炎可能使急性心肌梗塞（MI）过程复杂化，可能在MI后不久发生。 尽管心肌梗塞后心包炎通常是短暂性和自限性的，但症状并不舒服，并可能与潜在的复发性心肌缺血相混淆。 心肌梗塞后心包炎的发生率在再灌注时期之前高达20％，纤维蛋白溶解治疗后降至约5％，但主要经皮冠状动脉介入治疗（PCI）发生心包炎的发生率不详。 在2000年至2013年期间的一组以ST段抬高MI（STEMI）为标准的以色列患者中（其中三分之二的患者接受了主要再灌注治疗，主要为PCI），仅有1.2％发生MI后心包炎。 除了降低死亡率和其他主要不良心脏事件外，直接PCI还可能降低MI后心包炎的发生率。
There are scarce contemporary data regarding the incidence and prognosis of early postmyocardial infarction pericarditis (PMIP). Thus, we retrospectively analyzed 6,282 patients with ST-segment elevation myocardial infarction (STEMI) enrolled with known PMIP status in the Acute Coronary Syndrome Israeli Survey 2000 to 2013 registry. The primary outcome was the composite of all-cause mortality, nonfatal myocardial infarction, cerebrovascular event, stent thrombosis, or revascularization. The secondary outcomes were mortality and length of stay during the acute hospitalization. Overall, 76 patients with STEMI had PMIP (1.2%). PMIP incidence gradually decreased from 170 per 10,000 in 2000 to 110 per 10,000 in 2013, respectively (35% reduction, p for trend = 0.035). Patients with PMIP were younger (median 58.0 vs 61.0; p = 0.045), had less hypertension, higher cardiac biomarkers, and more frequently reduced left ventricular ejection fraction (87.0% vs 67.0%; p = 0.001). Patients with PMIP had longer time to reperfusion (225 minutes vs 183 minutes; p = 0.016) and length of stay (7.0 vs 5.0 days; p < 0.001). The composite end point occurred similarly inpatients with and without PMIP (10.5% vs 13.2%, respectively). There was no significant difference in 30-day, 1-year, and 5-year survival. In conclusion, PMIP is a relatively rare complication of STEMI in the coronary reperfusion era, portends worse short-term but not long-term outcomes, and is associated with bigger infarct size.
尽管不知道接受体外循环心脏手术患者的最佳红细胞输注阈值，但专家一般建议输血量低于8 g / dL的血红蛋白值。 在TRICS III试验中，超过5000名死亡高危成人被随机分配到限制性红细胞输注阈值（血红蛋白<7.5 g / dL输血）或自由阈值（血红蛋白<9.5 g / dL输血）。 任何原因导致的死亡，心肌梗死，卒中或新发的肾功能衰竭伴有透析的复合终点事件的发生率没有差异，而正如预期的那样，输血阈值较高的患者输血率较高。 该试验证实了小规模随机试验的结果，并支持我们的输血实践，将血红蛋白水平维持在8 g / dL以上，并认识到个别患者因素可能会改变此阈值。
BACKGROUND The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear.
METHODS In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was<7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was<9.5 g per deciliter in the operating room or intensive care unit [ICU]or was<8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes.
RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes.
CONCLUSIONS In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).
冠状动脉旁路移植手术（CABG）后给予长期阿司匹林预防大隐静脉移植物闭塞并减少心血管不良事件的发生率。 有人认为加入有效的P2Y12受体阻断剂如替格瑞洛可能会进一步改善预后。 在DACAB试验中，接受CABG的500名患者在术后24小时内被随机分配为替格瑞洛加阿司匹林，单用替格瑞洛或单用阿司匹林。 通过心血管成像确定的主要终点，一年的隐静脉移植通畅分别发生在三组静脉移植物中约89％，83％和77％。 虽然替卡格雷与阿司匹林的添加统计学上比单独使用阿司匹林更有效，但我们不推荐使用它，并担心增加出血风险的可能性，并等待临床结果的临床试验结果。
Importance The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown.
Objective To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG.
Design, Setting, and Participants Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017.
Interventions Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation.
Main Outcomes and Measures Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography.
Results Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone).
Conclusions and Relevance Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks.Trial Registration clinicaltrials.gov Identifier: NCT02201771.
β受体阻滞剂治疗减少射血分数降低（HFrEF）的心力衰竭患者的症状和死亡率，但β受体阻滞剂治疗对保留射血分数（HFpEF）的心力衰竭患者的疗效尚不确定。 一项单独的患者级荟萃分析评估了β受体阻滞剂对窦性心律患者心衰的疗效。 β受体阻滞剂治疗可降低HFrEF患者的死亡率和心血管死亡率，但HFpEF患者的小部分患者没有获益，尽管置信区间很大。 如果没有其他适应症，我们建议不要使用HFpEF的β受体阻滞剂。
Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials.
Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except forthose in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%]randomized to beta-blockers compared to 35/283 [12.4%]with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%]with beta-blockers and 26/283 [9.2%]with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis.
Conclusion Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
阿司匹林对心力衰竭窦性心律患者的安全性和有效性尚不确定。 在对无心房颤动病史的心力衰竭患者进行的一项登记研究中，3840名服用小剂量阿司匹林的患者倾向于同样数量的未服用阿司匹林的患者倾向匹配阿司匹林和非阿司匹林组的死亡率和卒中率相似。 然而，在阿司匹林组中观察到较高的心力衰竭再入院率，这在一些但不是全部的先前研究中已经观察到。 阿司匹林的使用也与心肌梗塞风险增加有关，但不能排除残余混杂。 我们建议不要使用阿司匹林治疗心力衰竭患者，而没有针对这种治疗的具体指征。
OBJECTIVES This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation.
BACKGROUND Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease.
METHODS The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission.
RESULTS The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use was not associated with an altered risk of composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.91 to 1.05), but it was associated with an increased risk of myocardial infarction (HR: 1.34; 95% CI: 1.08 to 1.67), whereas no differences were observed in all-cause mortality and stroke. An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result.
CONCLUSIONS No association was detected between low-dose aspirin use and the composite outcome of all-cause mortality,
左心室辅助装置越来越多地用于治疗晚期心力衰竭患者，尽管装置的耐用性受到泵血栓的限制。 在366名晚期心脏衰竭患者中，将磁悬浮离心流泵（设计为将泵血栓形成的风险降至最低）与轴流泵进行比较的试验中，关于复合材料，离心流动泵优于轴流泵 主要结果（两年免于中风或无需再次手术以替换或移除故障设备）。 两个治疗组的死亡率和致残性卒中发生率相似。 磁悬浮离心流泵是最常用的轴流装置的替代品，因为此离心流泵可提供更高的泵耐用性（由于泵血栓率较低）。
BACKGROUND In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure.
METHODS In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of>3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points.
RESULTS Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%]vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02).
CONCLUSIONS In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).
对于需要血运重建的稳定多支冠状动脉疾病（CAD）患者，经皮冠状动脉介入治疗（PCI）和冠状动脉搭桥手术（CABG）之间的选择可能很困难。 2018年对来自11项比较两种血运重建策略的随机试验的个体患者数据汇总分析显示，多支血管病患者的5年全因死亡率高于PCI。 然而，预先指定的亚组分析发现，没有糖尿病的患者和疾病较轻的患者的CABG没有显着的死亡率益处。 这项荟萃分析提高了我们的舒适度，提供PCI作为无糖尿病或复杂疾病患者的CABG替代方案。
BACKGROUND Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies.
METHODS We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics.
FINDINGS We included 11 randomised trials involving 11?518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR]1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score.
INTERPRETATION CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease.Longer follow-up is needed to better define mortality differences between the revascularisation strategies.
BACKGROUND Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT).
METHODS In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22.
FINDINGS Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR]0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%)in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23).