Antiplatelet therapy in percutaneous coronary intervention: A critical review of the 2007 AHA/ACC/SCAI guidelines and beyond

Antiplatelet therapy is a mainstay in the treatment of patients who have undergone percutaneous coronary intervention (PCI). Although the 2007 PCI treatment guidelines were published by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions, new clinical evidence has emerged, expanding our understanding of antiplatelet use and potentially affecting the treatment guidelines. For example, clinical trial results prompted a Science Advisory to recommend that dual therapy with aspirin and clopidogrel be used for longer periods—up to 1 year in patients who receive bare metal stents and at least 1 year in patients receiving drug‐eluting stents. New trial results have also emerged regarding the use of glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban. This article reviews the current recommendations for antiplatelet therapy in PCI patients, recent trial results, newly developed agents, ongoing clinical trials, and the future direction of antiplatelet therapy in patients who undergo PCI. © 2009 Wiley‐Liss, Inc.     

Clinical trials in interventional cardiology.

Several well-designed, randomized trials and registries have recently been completed in patients undergoing percutaneous coronary intervention (PCI) for the treatment of symptomatic coronary artery disease. These studies have further clarified the value of newer pharmacologic and mechanical approaches to patients with atherosclerotic disease and have resulted in improved clinical outcomes in patients undergoing PCI. As a result, many of the older paradigms of lesion-specific device selection have been revised to include the intricate balance of devices and drugs, tailored to the specific clinical presentation and lesion morphology in patients undergoing PCI. This article reviews several recent clinical trials and discusses their impact on early and late outcomes in patients undergoing PCI for symptomatic coronary artery disease.     

Timing,Selection, Modulation,and Duration of P2Y12 Inhibitors for Patients With Acute Coronary Syndromes Undergoing PCI

Dual antiplatelet therapy with aspirin and the oral P2Y₁₂ inhibitor clopidogrel as the cornerstone of treatment for patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) was firstly established in 2001. Soon thereafter, the newer-generation P2Y₁₂ inhibitors prasugrel and ticagrelor became commercially available. The clinical management of ACS patients undergoing PCI has evolved significantly in the last 2 decades, with a shift toward more rapid invasive management, broader use of drug-eluting stents, and the increasing recognition that major bleeding due to antiplatelet therapy is detrimental. In this ever-changing scenario, numerous studies have addressed 4 main questions regarding P2Y₁₂ inhibition in ACS patients undergoing PCI: timing, selection, modulation, and duration. This paper reviews the latest evidence surrounding these topical questions, with a focus on efficacy and safety data, practice guidelines, and residual areas of uncertainty.     

Anticoagulation strategies for patients undergoing percutaneous coronary intervention: unfractionated heparin, low-molecular-weight heparins, and direct thrombin inhibitors

Low-molecular-weight heparins and direct thrombin inhibitors are emerging as alternative anticoagulants to unfractionated heparin in patients undergoing percutaneous coronary intervention (PCI). This paper reviews the pharmacologic properties of these newer antithrombotic agents and evaluates the clinical data demonstrating their use in patients undergoing PCI.     

Revascularization of unprotected left main coronary artery disease: Strategy selection and systematic risk assessment

Refinement of interventional techniques, adjunctive pharmacological therapy, and the introduction of drug eluting stents have fostered new interest for the percutaneous treatment of unprotected left main coronary artery (ULMCA) stenosis. Several observational registries, some randomized controlled trials and several meta‐analyses have consistently shown no difference in mortality and myocardial infarction between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with ULMCA stenosis, but a higher rate of target vessel revascularization in patients treated with PCI. As a consequence, PCI of ULMCA stenosis has been upgraded to class IIa or IIb indication in the current European or American College of Cardiology/American Heart Association practice guidelines. Although these results are promising, they do not still represent enough evidence for extending PCI of ULMCA stenosis to current clinical practice. The EXCEL trial will address the value of PCI in relation to CABG for the treatment of ULMCA stenosis in more than 2000 patients. A major breakthrough of the SYNTAX trial has been the demonstration of an interaction between the coronary complexity and the revascularization strategy, suggesting that optimal risk stratification is a key element when deciding the best strategy of revascularization in this high‐risk group of patients. Multidisciplinary team approach remains essential to provide a balanced information to the patient and to offer the beast treatment option. © 2012 Wiley Periodicals, Inc.     

Thrombusaspiration bei Patienten mit akutem Myokardinfarkt

Recent advances in percutaneous coronary intervention and antiplatelet therapy as well as faster door-to-balloon times have markedly improved the therapy of patients with acute myocardial infarction. However, impaired myocardial perfusion despite revascularization of the infarcted vessel remains an ongoing problem with high prognostic relevance. In initial clinical trials thrombus aspiration in addition to conventional percutaneous coronary intervention demonstrated benefits regarding coronary flow and myocardial perfusion and was therefore recommended in practice guidelines. These improvements in surrogate endpoints did not translate into a favorable clinical outcome in recent large-scale multicenter randomized trials investigating the routine use of thrombus aspiration in patients with acute myocardial infarction. Furthermore, an increased risk of stroke after thrombus aspiration raises safety concerns. Therefore, thrombus aspiration has been downgraded in the recent guideline updates. The current article reviews the evidence from clinical trials and the recommendations in practice guidelines regarding thrombus aspiration in acute myocardial infarction.     

Optimal medical therapy is a proven option for chronic stable angina

The authors of the meta-analysis of a percutaneous coronary intervention (PCI)-based invasive strategy for improving prognosis for the treatment of angina conclude that a pooling of data from various studies can be sufficiently powered to evaluate the impact of PCI on long-term mortality. However, most randomized coronary artery patient trials have insufficient power to detect significant differences in hard end points. Randomized trials in patients with chronic stable angina enroll few patients who are over age 65 years, have depressed ventricular function, have clinical instability, or who have undergone previous coronary artery bypass grafting (CABG) or PCI. "Medical therapy" today no longer means the absence of PCI, but rather the presence of intensive, evidence-based pharmacologic intervention. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial randomized 2,287 patients to optimal medical therapy alone or optimal medical therapy plus PCI. Optimal medical therapy consisted of antiplatelet therapy, anti-ischemic therapy, and aggressive lipid and blood pressure control. Based on the strength of the evidence, the author of this commentary recommends more-aggressive medical therapy for patients with moderate-to-severe angina, and PCI or CABG for many patients in whom symptoms persist. Optimal medical therapy is a proven option for chronic stable angina.     

The role of PCI and CABG in the management of coronary artery disease in patients with diabetes

The role of percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) in patients with diabetes mellitus (DM) is evolving. Data from clinical trials and observational studies are reviewed as well as current clinical practice guidelines. The importance of aggressive medical therapy to achieve recommended glycemic control targets, and management of usual risk factors in patients with coronary artery disease (CAD) cannot be overemphasized regardless of the revascularization therapy selected. Patients with type 2 diabetes are at increased risk for CAD, which is the cause of death in the majority of patients. Outcomes following PCI and CABG are worse in patients with DM compared to those without DM. This calls for randomized trials and other studies focused on patients with DM.     

Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications. METHODS: This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).     

Coronary revascularization for patients with unprotected left main coronary artery disease: Evidence,guidelines, and judgment! making clinical decisions in 2009

The current clinical practice guidelines categorize the use of coronary artery bypass graft (CABG) surgery for revascularization of patients with unprotected left main coronary artery disease (ULMCAD) as a class IA recommendation while it categorize the use of percutaneous coronary interventions (PCI) as a class III recommendation. The evidence underlying these recommendations is weak and out dated. The purpose of this review is to critically reevaluate current state‐of‐the‐art with respect to revascularization of patients with ULMCAD who are acceptable surgical candidates. In doing so we will highlight the divergence between practice guidelines and patient‐centered clinical decision‐making; critically appraise the “evidence” underlying the current practice guidelines; review the emerging data regarding utility of CABG versus PCI in these patients; and finally discuss the elements of a contemporary approach to clinical decision‐making in light of the current state of knowledge. © 2009 Wiley‐Liss, Inc.     

Examining Coronary Revascularization Practice Patterns for Diabetics: Perceived Barriers,Facilitators, and Implications for Knowledge Translation

BackgroundThe FREEDOM trial provided robust evidence that coronary artery bypass grafting (CABG) was superior to percutaneous coronary intervention (PCI) for coronary revascularization in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MV-CAD). The present study examined practice pattern changes and perceived barriers and facilitators to implementing FREEDOM trial evidence in British Columbia (BC).MethodsUsing a population-based database of cardiac procedures in BC, PCI:CABG ratios from 2007-2014 were compared before and after publication of the FREEDOM trial in the 4 tertiary cardiac centres that provided both CABG and PCI. Surveys of barriers and facilitators to implementation of evidence in practice were completed by 57 health care providers (HCPs) attending educational outreach sessions conducted in 2016-17 at 5 tertiary cardiac centres in BC.ResultsThe overall PCI:CABG ratio declined from 1.59 (95% confidence interval [CI] 1.48-1.70, range 1.16-1.86) before publication to 0.88 (95% CI 0.75-1.01, range 0.56-0.82) after publication (P < 0.01). This decline from before to after publication was significant in 3 centres, but not in the fourth centre (from 1.62 to 1.49; P = 0.61). Barriers were identified at the levels of evidence (applicability, credibility), HCP (awareness/knowledge, practice behaviours), patient (knowledge/misconceptions, preferences), and systems (siloing of care, financial disincentives, resource limitations, geography). Facilitators were additional studies/guidelines, education/dissemination, shared decision making, a heart team approach, changes to remuneration models, and increased resources.ConclusionsFollowing publication of the FREEDOM trial, the proportion of patients with DM and MV-CAD undergoing CABG increased in BC; however, practice patterns varied across cardiac centres. HCPs attributed these practice variations to multilevel barriers and facilitators. Future knowledge translation strategies should be multifaceted and tailored to identified determinants.     

Popular procedures without evidence of benefit: A case study of percutaneous coronary intervention for stable coronary artery disease

Despite limited benefit, percutaneous coronary intervention (PCI) remains a common procedure that is often performed for uncertain or inappropriate indications in patients with stable coronary artery disease (CAD). PCI cases per capita have increased year-over-year in most European countries, and many have higher rates than the U.S. Meanwhile, first-line therapy such as optimal medical therapy (OMT) and lifestyle changes, continue to be under-utilized. This article reviews the evidence on use of PCI in stable CAD. Specifically, we analyzed randomized control trials, systematic reviews, appropriate use criteria, and professional society guidelines that examine the risks and benefits of PCI compared to OMT. We then highlight utilization patterns as well as interventions that better align current practice with evidence-based care.     

Narrative review: reperfusion strategies for ST-segment elevation myocardial infarction

Optimal treatment for ST-segment elevation myocardial infarction depends on early diagnosis and rapid selection of the appropriate reperfusion strategy. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at PCI-capable hospitals. For hospitals without PCI capability, there are 2 reperfusion strategies, primary PCI and thrombolytic therapy, which are both supported by clinical evidence and national guidelines. Transferring patients for primary PCI may cause delays and requires established, proven protocols, systems, and networks to achieve minimal door-to-balloon times. The authors review the available data and present a systematic, evidence-based approach in a simple framework to enable noncardiovascular and cardiovascular physicians to select the optimal reperfusion strategy. The framework is based on available data from clinical trials and local circumstances from clinical practice by incorporating duration of symptoms (fixed ischemia time) and anticipated transport delays to a PCI-capable facility (incurred ischemia time).     

Glycoprotein receptor inhibitors in the management of acute coronary syndromes

Coronary thrombosis and the risk of clinical adverse events remains high despite considerable advances in the management of acute coronary syndromes (ACS) with the combined use of aspirin, heparin, fibrinolytic therapy, and percutaneous coronary intervention (PCI). Platelet aggregation and thrombosis play a key role in the pathogenesis of unstable coronary syndromes. Over the past several years, multiple placebocontrolled trials involving more than 50,000 ACS patients have shown that blockade of the platelet receptor glycoprotein (GP) IIb/IIIa, the final pathway in platelet aggregation, reduces the incidence of ischemic complications among patients with ACS. Three agents (abciximab, eptifibatide, and tirofiban) are currently approved for use with aspirin and heparin in the management of ACS or during percutaneous coronary intervention. They have consistently been shown to reduce the incidence of death or myocardial infarction in the ACS population including the patients not routinely scheduled for early revascularization. They provide an augmented treatment effect among high-risk ACS patients, particularly those who have a baseline troponin-t-positive status. Recently published practice guidelines have recommended their use in high-risk patients with ACS and all those undergoing PCI.     

Pharmaco-invasive strategies expand access to percutaneous coronary intervention in ST-elevation myocardial infarction

Primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion in patients with ST-elevation myocardial infarction (STEMI). Therefore, increasing timely access to PCI is a major national focus. The majority of United States hospitals are not PCI capable, which has stimulated the development of regional STEMI programs using standardized protocols and organized transfer systems. These regional STEMI systems have improved treatment times and clinical outcomes, leading to a recent class I recommendation in the American College of Cardiology/American Heart Association guidelines to develop STEMI systems of care. Despite this, less than 15% of patients transferred from non-PCI hospitals to PCI centers have total door-to-balloon times less than 2 hours. We review the therapeutic options for the STEMI patient with expected delay to PCI focusing on recent pharmacoinvasive trials. Based on these trial results, recent guidelines recommend early transfer and cardiac catheterization for patients treated with fibrinolytic therapy.     

Guidelines to Practice Gap in the Use of Glycoprotein IIb/IIIa Inhibitors: From ISAR‐REACT to Overreact?

Adjunctive use of glycoprotein IIb/IIIa inhibitors (GPI) is associated with favorable outcomes following percutaneous coronary intervention (PCI). Guidelines for use of GPI have been published by various national societies including National Institute of Clinical Excellence (NICE), United Kingdom. The latter has not been updated since publication. The impact of contemporary trials such as ISAR-REACT (which showed no benefit of abciximab and 600 mg of clopidogrel compared with 600 mg of clopidogrel alone, in elective patients) on adherence to NICE guidelines is unknown.
Methods: We audited use of GPI against NICE guidelines following publication in May 2002. Data were collected from 1,685 patients between September and November in years 2002, 2003, 2004, and 2007.
Results: In 2002 and 2003, only 10.2% and 11.8%, respectively, of patients were noncompliant to NICE guidelines. Over time, there was an increase in patients not given GPI despite meeting NICE criteria. After publication of ISAR-REACT, the comparative figures for noncompliance in 2004 and 2007 were 40.0% and 44.5%. A similar pattern was seen in patients with diabetes; in 2002 and 2003 noncompliance was 16.7% and 11.1%, respectively, and in 2004 and 2007 noncompliance was 38.0% and 44.7%, respectively. Qualitatively, similar findings were recorded in patients with NSTE-ACS. The overall noncompliance to NICE guidelines increased from 11.0% to 42.1% (P < 0.0001) after the ISAR-REACT study.
Conclusions: We found a decline in compliance to NICE guidelines on GPI usage during PCI. This was likely influenced by contemporary trials demonstrating little or no benefit of GPI in patients undergoing elective PCI who are adequately pretreated with clopidogrel. Our findings suggest the need for a mechanism whereby regular updates to guidelines can be disseminated following new trial evidence.     

Treatment of Patients with Left Main Coronary Artery Disease

Considering lesion priority and its clinical consequences, coronary artery bypass grafting (CABG) has been a treatment of choice for revascularization in patients with significant left main coronary artery (LMCA) disease, However, with remarkable advancements in techniques of percutaneous coronary intervention (PCI), supporting devices, and adjunctive pharmacologic therapy, PCI with stenting has emerged to be a less invasive and feasible revascularization treatment for these patients. The cumulative evidence suggests that the safety outcomes such as mortality or composite of death, myocardial infarction, and stroke are similar among PCI and CABG, with the only difference being the rate of repeat revascularization. Based on these data, the current guideline of revascularization of LMCA disease has adopted an increasing off-label experience with stenting and clinical studies and been updated to partly approve PCI as a viable alternative (in level of class IIb) in selected patients. The choice of PCI or CABG for unprotected LMCA disease depends on several clinical and anatomic features, ensuring crucial patient selection to be a cornerstone for achieving favorable long-term outcomes. In patients with very complex anatomic features and concomitant diffuse multivessel disease, CABG is preferred so as to avoid procedural and future thrombotic risks and to provide more complete revascularization. By contrast, in patients with relatively simple LMCA disease, such as ostial/shaft LMCA disease, isolated LMCA disease (with or without one or two-vessel involvement), and LMCA disease with low SYNTAX score, PCI is an alternative, and in some cases a preferred, strategy to reduce surgical risks (eg, stroke and in-hospital events following major surgery). For the future, ongoing large clinical trials might also boost interventional cardiologists to select PCI with stenting as an alternative revascularization strategy for unprotected LMCA disease. This evidence will most likely change the current clinical practice and guidelines of optimal revascularization strategy for unprotected LMCA disease.     

Day 1 care in patients with non-ST-segment elevation myocardial infarction

In 2007, the American College of Cardiology/American Heart Association and the European Society of Cardiology updated their guidelines for the management of patients with non-ST-segment elevation myocardial infarction (NSTEMI). Based on evidence from recent clinical studies, both 2007 guidelines recommend early risk stratification, administration of appropriate pharmacologic therapy, and selective use of percutaneous coronary intervention in order to reduce morbidity and mortality in these patients. In this article, we focus on management of patients with NSTEMI during the first 24 h of presentation and present a clinical scenario to illustrate the current guidelines-based management strategy.     

GP IIb/IIIa inhibitors during primary percutaneous coronary intervention for STEMI: New trial and registry data

Primary percutaneous coronary intervention (PCI) with adjunctive glycoprotein (GP) IIb/IIIa receptor inhibitor therapy administered in the cardiac catheterization laboratory is the optimal reperfusion strategy for patients with ST-elevation myocardial infarction. Most available data regarding these agents are from trials comparing abciximab to placebo alone. Noninferiority trials comparing small-molecule GP IIb/IIIa receptor inhibitors, such as tirofiban and eptifibatide with abciximab, have used markers for myocardial reperfusion as primary end points but are underpowered to detect significant differences in hard clinical outcomes. Such a trial would need to enroll a very large number of patients and thus make it practically impossible to perform. Registry data reveal that most patients undergoing primary PCI are treated with small-molecule GP IIb/IIIa receptor inhibitors in clinical practice, and no observed difference is observed in safety and efficacy when compared with patients treated with abciximab therapy.     

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty,stents and coronary artery bypass grafting

Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.