Management of Acute Coronary Syndromes in Patients with Diabetes: Implications of the FREEDOM Trial

Background

Diabetes mellitus (DM) is a powerful independent risk factor for multivessel, diffuse coronary artery disease (CAD). The optimal coronary revascularization strategy in DM is not clearly defined, but past trials have suggested an advantage for coronary artery bypass grafting (CABG). Recently, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial found patients randomized to CABG had lower rates of death and myocardial infarction (MI) compared with those randomized to percutaneous coronary intervention (PCI).

Objective

This article reviews the contemporary management of patients with DM presenting with acute coronary syndromes, particularly ST-elevation MI, in the post-FREEDOM era.

Methods

We undertook a comprehensive review of published literature addressing trials in this field performed to address current knowledge both in the pre- and post-FREEDOM era.

Results

The implications of FREEDOM for patients with acute coronary syndrome are that CABG provides a significant benefit, compared with PCI with drug-eluting stents, to patients with DM and multivessel coronary artery disease; and that patients similar to those enrolled in FREEDOM should receive CABG in preference to PCI. The relevance of FREEDOM’s findings to the large proportion of patients who would not meet inclusion criteria—including patients with an acute coronary syndrome undergoing an early or emergent invasive strategy, remains uncertain.

Discussion

FREEDOM’s outcomes have generated uncertainty regarding best practice once thrombolysis in myocardial infarction grade 3 flow is re-established in patients with DM and multivessel disease. Current interventional guidelines recommend optimally treating the culprit artery; however, decisions made at the time of revascularization influence future revascularization strategies, particularly stent choice and resultant P2Y₁₂ receptor antagonist therapy. The preferred method for future revascularization may be questioned if the patient's residual coronary stenoses do not, post-PCI, meet the FREEDOM inclusion criteria, or where the left anterior descending artery is the infarct-related artery, and after left anterior descending artery PCI the patient would not receive an internal mammary graft. The management of residual disease and the preferred (further) revascularization strategy needs to be tested in an appropriately powered randomized trial.

Conclusions

The optimal revascularization strategy in patients with acute coronary syndrome, diabetes, and multivessel disease, in particular those with ST elevation, is unclear, and not guided by level A (or B) evidence. Currently CABG is favored over PCI, and an individually tailored, collaborative approach, guided by a multidisciplinary heart team, should be employed.     

Role of surgical revascularization in diabetic patients with coronary artery disease

Diabetes is a well-known risk factor for morbidity and mortality associated with coronary artery disease. Currently, diabetics represent approximately a quarter of patients requiring coronary revascularization in the USA. The purpose of this article is to review and analyze the available data in surgical revascularization of diabetic patients with coronary artery disease. The review will also examine new developments in myocardial revascularization and assess their probable impact on the long-term outcome of diabetic patients.     

Tackling the thrombotic burden in patients with acute coronary syndrome and diabetes mellitus

Patients with diabetes mellitus (DM) and coronary artery disease, particularly those presenting with acute coronary syndromes (ACS), have a higher risk of developing ischemic complications than their nondiabetic counterparts. Although ACS patients with DM benefit more than normoglycemic ACS patients from early coronary angiography and revascularization, they remain at a higher risk of complications following percutaneous coronary intervention and bypass surgery. The DM-associated prothrombotic state has been implicated in the pathogenesis of these complications and growing data supports the notion that potent platelet inhibition is of paramount importance in order to optimize outcomes of DM patients presenting with ACS. This article focuses on the evidence supporting the concept that augmented platelet reactivity and impaired responsiveness to oral antiplatelet agents are influential drivers of the increased propensity of DM patients with ACS to develop thrombotic complications. In particular, strategies to enhance platelet P2Y₁₂ receptor inhibition, a key factor to improve outcomes in this patient population, are reviewed.     

老年冠心病合并2型糖尿病患者冠状动脉造影结果分析

目的探讨合并2型糖尿病的老年冠心病患者冠状动脉造影的特点。方法 50例老年冠心病合并2型糖尿病患者（糖尿病组）与50例老年冠心病未合并2型糖尿病患者（对照组）,均行冠状动脉造影检查,并进行比较。结果糖尿病组冠状动脉造影主要表现为多支病变和多支多节段病变,对照组主要表现为单支病变和2支单节段病变;糖尿病组单支病变、多支病变、弥漫性狭窄病变、重度及闭塞病变发生率分别为14%,58%,78%和88%;对照组分别为44%,26%,20%和40%,2组比较差异均有统计学意义（P〈0.05）。结论老年冠心病合并2型糖尿病者冠状动脉的狭窄程度较未合并2型糖尿病者重。     

Tackling the thrombotic burden in patients with acute coronary syndrome and diabetes mellitus

Patients with diabetes mellitus (DM) and coronary artery disease, particularly those presenting with acute coronary syndromes (ACS), have a higher risk of developing ischemic complications than their nondiabetic counterparts. Although ACS patients with DM benefit more than normoglycemic ACS patients from early coronary angiography and revascularization, they remain at a higher risk of complications following percutaneous coronary intervention and bypass surgery. The DM-associated prothrombotic state has been implicated in the pathogenesis of these complications and growing data supports the notion that potent platelet inhibition is of paramount importance in order to optimize outcomes of DM patients presenting with ACS. This article focuses on the evidence supporting the concept that augmented platelet reactivity and impaired responsiveness to oral antiplatelet agents are influential drivers of the increased propensity of DM patients with ACS to develop thrombotic complications. In particular, strategies to enhance platelet P2Y(12) receptor inhibition, a key factor to improve outcomes in this patient population, are reviewed.     

Prevention of acute coronary events in noncardiac surgery: β-blocker therapy and coronary revascularization

During major vascular surgery, patients are at high risk for developing myocardial infarction and myocardial ischemia, and two risk-reduction strategies can be considered prior to surgery: pharmacological treatment and prophylactic coronary revascularization. β-blockers are established therapeutic agents for patients with hypertension, heart failure and coronary artery disease. There is still considerable debate concerning the protective effect of β-blocker therapy towards perioperative coronary events, which will be outlined in this article. Two randomized, controlled trials suggest that coronary revascularization of cardiac-stable patients provides no benefits in the postoperative outcomes. In the current American College of Cardiology/American Heart Association guidelines for ‘Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery’, routine prophylactic coronary revascularization is not recommended in patients with stable coronary artery disease. However, a recent retrospective, observational study suggests that intermediate-risk patients may benefit from preoperative coronary revascularization. The present article provides an extended overview of leading observational studies, randomized, controlled trials, meta-analyses and guidelines assessing perioperative β-blocker therapy and prophylactic coronary revascularization.     

Role of surgical revascularization in diabetic patients with coronary artery disease

Diabetes is a well-known risk factor for morbidity and mortality associated with coronary artery disease. Currently, diabetics represent approximately a quarter of patients requiring coronary revascularization in the USA. The purpose of this article is to review and analyze the available data in surgical revascularization of diabetic patients with coronary artery disease. The review will also examine new developments in myocardial revascularization and assess their probable impact on the long-term outcome of diabetic patients.     

残存SYNTAX评分对311例冠心病PCI患者长期预后评价

目的 评价残存SYNTAX评分对冠心病经皮冠状动脉介入治疗（percutanous coronary intervention,PCI）患者长期预后的预测能力。 方法 连续入选2013年1月至2014年5月于内蒙古自治区人民医院心内科一病区住院冠心病并行PCI患者311例,收集性别、年龄、临床诊断、血脂、肾功能等临床资料,进行SYNTAX评分和残存SYNYTAX评分,同时进行2~4年临床随访,随访不良心脑血管事件（MACCE）,包括全因死亡、卒中、血运重建、心力衰竭。 结果 311例患者发生MACCE 48例,其中全因死亡14例;再次血运重建23例;缺血性卒中9例;心力衰竭2例。MACCE组与无MACCE组比较年龄大（64.13±8.45岁 vs 60.79±10.12岁,P=0.03）、糖尿病患者比例高（39.58% vs 18.63%,P=0.001）、SYNTAX评分高（15.16±6.53 vs 12.94±7.44,P=0.017）和残存SYNTAX评分高（7.52±6.54 vs 4.23±5.50,P=0.000)。SYNTAX评分、残存SYNTAX 评分、目测冠状动脉病变预测终点事件的曲线下面积分别为0.608（P=0.018）、0.665(P=0.000)、0.668(P=0.000)。完全血运重建组与不完全血运重建组MACCE发生率分别为5.98%和20.42%(P=0.003),两组再次血运重建率分别为0.85%和12.37%(P=0.000)。糖尿病患者和非糖尿病患者SYNTAX评分为15.09±7.69和12.78±7.17(P=0.026),残存SYNTAX评分为6.15±6.32和4.34±5.57(P=0.016)。糖尿病患者和非糖尿病患者MACCE发生率分别为27.9%和11.8%(P=0.001),再次血运重建率分别为19.1%和4.9%(P=0.000)。 结论 ①冠心病PCI患者完全血运重建优于不完全血运重建,残存冠状动脉病变越多MACCE发生率越高。②残存SYNTAX评分、SYNTAX评分和冠状动脉病变均能预测长期预后。③糖尿病患者冠状动脉病变程度重,MACCE发生率高,主要原因是再次血运重建。     

冠状动脉慢性完全闭塞病变患者碎裂QRS波与疾病严重程度及预后的关系

目的分析冠状动脉慢性完全闭塞病变患者碎裂QRS波(f QRS)与疾病严重程度及预后的关系。方法选择2012年11月至2017年11月我院接收的76例冠状动脉慢性完全闭塞病变患者为研究对象,均采用血运重建术进行治疗,分析不同严重程度患者f QRS出现情况及治疗效果。结果 3支冠状动脉病变患者f QRS出现率明显高于1~<3支冠状动脉病变患者(P<0.05)。≥2 cm冠状动脉完全闭塞患者f QRS出现率明显高于<2 cm短段冠状动脉病变患者(P<0.05)。有f QRS患者临床治疗总有效率明显低于无f QRS患者(P<0.05)。结论 f QRS可反映冠状动脉慢性完全闭塞病变严重程度,有f QRS的冠状动脉慢性完全闭塞病变患者经血运重建术治疗预后情况较差。     

How to revascularize patients with diabetes mellitus—

Summary The diabetic patient is at high risk for coronary artery disease. Incidence as well as severity of the disease is highly increased in comparison to non–diabetic patients. The revascularization of the diabetic patient is a great challenge, since the longterm results are disappointing when compared to non–diabetic patients. The success of coronary artery bypass grafting is limited by increased perioperative mortality and a faster occlusion of especially venous bypass grafts. In percutaneous interventions the excessive high restenosis rates worsen longterm results. Several clinical trials investigated the outcome of the two revascularization strategies and could demonstrate at least a tendency towards better results when the operative approach was chosen. Particularily, the BARI trial showed reduced mortality for surgery when compared to percutaneous coronary interventions. However, in this trial, in 87% of patients undergoing bypass surgery all stenoses were succesfully treated, whereas in patients undergoing percutaneous coronary intervention only 76% of all stenoses were primarily succesfully treated. In addition, no stents were used in this trial. Furthermore, the enrollment of the previous trials dates one decade ago. These trials do therefore not necessarily represent the current standard therapy, especially for percutaneous coronary interventions. The restenosis rate could be decreased in recent years by means of drug–eluting stents and an aggressive antiplatelet therapy from more than 50% to less than 10% leading to considerably improved long–term results. Therefore, percutaneous coronary interventions have developed to be a reasonable alternative to bypass surgery. Different clinical trials are currently underway (BARI 2D, CarDIA, FREEDOM) comparing the outcome of the two approaches.     

Comparative effectiveness of revascularization strategies in stable ischemic heart disease: current perspective and literature review

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are established strategies for coronary revascularization in the setting of ischemic heart disease. Multiple randomized controlled trials and observational studies have compared the impact of the two modalities on the patients’ quality of life, mortality and morbidity, as well as the cost–effectiveness of these modalities in different clinical setting. CABG is the preferred strategy for revascularizations in patients with multi-vessel disease, especially in those with higher risk secondary to associated diabetes, left ventricular dysfunction or more complex lesions. PCI is a reasonable revascularization modality in patients with ischemia and single or low-risk multi-vessel disease and those with unprotected left main with low complexity anatomy. Compared with PCI, CABG is associated with less repeat revascularization, better quality of life and improved survival in high-risk patients. Although CABG is associated with higher cost, it is probably associated with a reasonable cost per quality-adjusted life-year gained in many patients. Therefore, CABG will often be a cost-effective strategy, especially in patients with high angiographic complexity and/or diabetes.     

“一站式”冠状动脉搭桥及颈动脉支架植入术的初步尝试

目的:尝试应用冠状动脉搭桥术及颈动脉支架植入术"一站式"治疗冠心病合并严重颈内动脉狭窄。方法:选择复旦大学附属中山医院2例冠心病合并严重颈动脉狭窄的男性患者,给予其"一站式"冠状动脉搭桥术及颈动脉支架植入术,分析相应的围手术期治疗、手术方式及术后相关情况。结果:术后患者心功能改善。术后6个月颈动脉CTA提示支架通畅,患者无晕厥、黑朦症状。结论:"一站式"冠状动脉搭桥术及颈动脉支架植入术对冠心病合并颈动脉狭窄患者是较好的选择,但需要在杂交手术室进行,且对术者技术要求较高。     

Mid‐term outcome after carotid artery stenting depends on presence of coronary artery disease

BACKGROUND. Longer‐term outcome of patients following carotid artery revascularization depends predominantly on cardiac events rather than neurological events.

AIM. To assess the longer‐term outcomes of patients with known coronary artery morphology undergoing carotid artery stenting.

METHOD. In a prospective observational study including 549 consecutive patients undergoing carotid artery stenting, a coronary angiography was performed in a single session unless a recent angiogram was available. Following the intervention, patients were followed prospectively to determine neurological events as well as major adverse coronary events (MACE) during long‐term follow‐up.

RESULTS. Coronary artery disease was present in 378 patients including 92 patients without current significant stenosis. The MACE rate was 6.4% in patients without coronary artery disease compared to 28.3% in patients with coronary artery disease (P<0.00001). Cardiac and all‐cause mortality were statistically significantly higher in patients with a significant coronary stenosis than in patients without coronary artery disease (P<0.001 and P<0.01). Cardiac mortality and all‐cause mortality were 2.3% and 7.6% in patients without coronary artery disease (patient group I), 7.6% and 13.0% in patients with coronary artery disease but no current significant stenosis (patient group II), and 10.5% and 16.1% in patients with significant coronary stenosis (patient group III). Neurological events, however, were distributed equally among the three patient groups.

CONCLUSIONS<1/emph>. In the longer term, outcomes in patients undergoing carotid artery stenting depend on concomitant coronary artery disease rather than neurological events, cardiac mortality and even all‐cause mortality depending on a significant coronary artery stenosis.     

Reviewing hybrid coronary revascularization: challenges,controversies and opportunities

Two main approaches to myocardial revascularization currently exist, coronary artery bypass and percutaneous coronary intervention. In patients with advanced coronary artery disease, coronary artery bypass surgery is associated with improved long term outcomes while percutaneous coronary intervention is associated with lower periprocedural complications. A new approach has emerged in the last decade that attempts to reap the benefits of bypass surgery and stenting while minimizing the shortcomings of each approach. This new approach, hybrid coronary revascularization, has shown encouraging early results. Minimally invasive techniques for bypass surgery have played a large part of bringing this approach into contemporary practice.     

冠心病患者糖耐量变化与冠状动脉病变之间的关系分析

目的 探讨冠心病患者糖耐量变化与冠状动脉病变之间的关系.方法 200例确诊为单纯冠心病患者分为糖耐量值正常(NGT)组132例,冠心病合并糖耐量异常(IGT)组35例,冠心病合并2型DM(T2DM)组33例.全部患者均行冠状动脉造影(CAG)与口服75 g葡萄糖耐量试验,对患者血糖、胰岛素以及血脂含量进行检测.冠状动脉病变程度用CAG进行分析,冠状动脉狭窄程度按照美国心脏病学会分类标准进行分类与评价.结果 ①NGT、IGT与DM组糖化血红蛋白(HbA1c)、空腹血糖(FBG)、餐后2小时血糖(PBG)、甘油三酯(TG)、高密度脂蛋白(HDL-C)差异有统计学意义(P<0.05),IGT组与NGT在空腹胰岛素(FINS)差异有统计学意义(P<0.05);②NGT、IGT与DM组右冠动脉(RCA)、左前降支冠状动脉(LAD)、左主干(LMT)相比,两两之间差异均具有统计学意义(P＜0.05),左回旋支(LCX)、总狭窄指数以及冠状动脉远端病变方面,IGT组与DM组较NGT组,差异均具有统计学意义(P＜0.05);③DM组Gensini积分为(144.32±22.90)分,IGT组为(94.29±16.83)分,NGT组(67.77±12.32)分,DM组与IGT组和NGT组比较,Gensini积分差异有统计学意义,但DM与IGT组间比较,差异无统计学意义(P＞0.05).结论 冠心病糖耐量变化与冠状动脉病变间具有一定的关联性,餐后高血糖可能是冠心病发生发展的主要原因.     

踝肱压力指数在诊断糖尿病女性冠心病的应用

目的女性冠状动脉疾病（cAD）的临床症状往往不定,尤其对患有糖尿病（DM）的女性,因此有必要通过简单的诊断测试,来确定高危糖尿病（DM）女性是否有患CAD的风险。方法本院疑似冠心病患者80例,其中DM患者34例。分别对患者行运动负荷心肌灌注成像和臂部、踝关节血压测量,以检测患者缺血性总灌注缺损大小（TPD）和踝肱压力指数（ABI）。结果缺血性TPD在男、女患者间比较无明显差异,而DM患者缺血性TPD明显大于无糖尿病患者;缺血性TPD在DM男、女患者中比较无明显差异;然而,ABI〈0．9的DM女性比ABI≥O．9的DM女性有较高的缺血性TPD,ABI值在男性中间比较无差异。结论ABI评估DM无症状女性CAD患者的发病是可行的,检测结果显示缺血性TPD〉10％是冠状动脉血运重建的一个显像指标。     

Controversies surrounding percutaneous coronary intervention in the diabetic patient

Diabetic patients with coronary artery disease are common and complex, with an aggressive progression of atherosclerosis, increased rate of stent complications, and increased rates of incomplete revascularization in multivessel disease compared to non-diabetic patients. In this review, we first discuss the pathophysiologic elements of insulin resistance and presentations of coronary artery disease in diabetic patients. Next, we outline the evolution and present the data on revascularization strategies on diabetic patient outcomes. The overall conclusion of our review is that a strategy of complete and durable revascularization and guideline-directed medical therapy currently provides the best possible chance at closing the gap between outcomes in patients with and without diabetes.     

慢性贫血对冠心病患者血运重建术后院内结果的影响

目的评价慢性贫血对冠心病患者血运重建术后院内临床结果的影响。方法选择2002年7月—2004年6月在首都医科大学附属北京安贞医院接受血运重建治疗（经皮冠状动脉介入治疗或冠状动脉旁路移植术）的3679例患者,按照世界卫生组织确定的贫血标准（血红蛋白：男性〈120g/L,女性〈110g/L）将患者分为贫血和非贫血两组。比较两组患者血运重建术后院内不良心脑血管事件（MACCE）的发生率（包括全因死亡、新发心肌梗死、卒中和再次血运重建）,并分析其可能的原因。结果3679例患者中有贫血患者426例（占11.6%）,非贫血患者3253例（占88.4%）。贫血组与非贫血组分别有10例（2.4%）和64例（1.9%）发生院内死亡（P〈0.05）;贫血组院内MACCE的发生率明显高于非贫血组（4.2%比3.2%,P〈0.05）,但两组新发心肌梗死（0.7%比0.6%）、卒中（1.2%比0.4%）和再次血运重建（0比0.2%）的发生率差异无统计学意义（P均〉0.05）。结论合并贫血的冠心病患者较非贫血患者血运重建术后院内MACCE发生率增加,其中全因病死率的增加更为显著。     

Reoperative off-pump coronary artery bypass grafting: current outcomes,concerns and controversies

Increasing numbers of patients have undergone coronary artery bypass grafting in the last four decades. As a result, the incidence of reoperative coronary artery bypass grafting is rising. Reoperative procedures pose several technical difficulties and are associated with increased operative risks, which exceed those of the initial revascularization. As the incidence of reoperative procedures is increasing so is the experience of reoperative coronary artery bypass grafting, with the resultant evolution of several alternative strategies to lower the operative risks. These strategies include alternative techniques for re-entry, strict avoidance of graft manipulation to minimize the risk of graft atheroembolism, and modification of the method of myocardial protection, depending on the status of the native coronary circulation and the patency of venous or arterial grafts. Off-pump coronary artery bypass grafting is one such technique that, through the avoidance of inherent risks of cardiopulmonary bypass, has the potential to reduce the morbidity associated with reoperative coronary artery bypass grafting. This article evaluates the current outcomes of reoperative off-pump coronary artery bypass grafting, and highlights the concerns and controversies associated with this strategy.     

Developments in surgical revascularization to achieve improved morbidity and mortality

Coronary artery bypass graft surgery remains the main treatment modality for multivessel coronary artery disease and has consistently been demonstrated to have significantly lower rates of major adverse cardiac and cerebrovascular events in comparison to percutaneous coronary intervention. In this article we will explore the advances over time and the recent refinements in the techniques of surgical revascularization and how these contribute to the superior outcome profile associated with coronary artery bypass graft surgery. These include the current outcome status of coronary artery bypass grafting; the major landmark trials, registries and meta-analyses comparing coronary artery bypass grafting and percutaneous coronary intervention; the developments in coronary artery disease lesion classification; the techniques for the physiological assessment of coronary artery lesions; bypass grafting using arterial conduits; the role of off-pump coronary artery surgery; the outcomes of reoperative surgery; hybrid techniques for coronary revascularization; minimally invasive coronary artery surgery and finally robotic surgery.