Ticagrelor vs Prasugrel in Patients With Diabetes and Multivessel Coronary Artery Disease

The SYNTAX score according to diabetic status: What does it mean for the patient requiring myocardial revascularization?

Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials

Randomized trials have largely demonstrated that percutaneous coronary intervention (PCI) with sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) results in a significant reduction in the occurrence of angiographic restenosis and revascularization compared with bare metal stents (BMS).1–4 The benefit of drug-eluting stents (DES) also has been confirmed in “real-world” scenarios. In this setting, when the analysis was focused on high-risk patient and lesion subgroups, a benefit still existed despite the presence of restenosis.5–7 These expanded indications do not yet cover many other types of complex lesions for which only registries or randomized trials, not yet published, are available so far (Tables 1 through 7⇓⇓⇓⇓⇓⇓). This topic is discussed in detail in this review. An important clarification is that the lack of proof is most probably due to the difficulty in performing randomized trials in high-risk groups using BMS as controls. It will be no surprise to find that the field in which DES perform best compared with BMS is likely to be complex lesions and patients8 (Figure 1). View this table: TABLE 1. DES in Unprotected Left Main Stenosis View this table: TABLE 2. DES in Bifurcation Lesions View this table: TABLE 3. DES in Chronic Total Occlusions View this table: TABLE 4. DES in Small-Vessel Disease and Long Lesions View this table: TABLE 5. DES in SVGs View this table: TABLE 6. DES in Acute MI View this table: TABLE 7. DES in Multivessel Disease Figure 1. Lesion complexity and stent performance in the BMS and DES eras. Adapted from Edelman et al.8 Current American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) guidelines consider the presence of a stenosis in the unprotected left main coronary artery (LMCA) a class IIa or IIb indication, respectively, for PCI if coronary artery bypass grafting (CABG) is not a viable option.9,10 Moreover, according to the AHA/ACC 2005 guidelines, in …

Reply: The forced correlation between ISCHEMIA and the inaccurate CABG recommendations of the 2021 American College of Cardiology/American Heart Association/Society for cardiovascular Angiography coronary revascularization guidelines

Background Potent P2Y12 inhibitors are recommended on top of aspirin in patients presenting with acute coronary syndrome (ACS). However, guideline recommendations suggest that the optimal antithrombotic strategy should be tailored based on patients thrombotic and hemorrhagic risk profile. Purpose It is poorly investigated if the benefits derived from potent P2Y12 inhibition in patients with ACS depend on the individual thrombotic risk profile. Our aim was to evaluate if the benefits associated with prasugrel vs. clopidogrel in patients with ACS undergoing percutaneous coronary intervention (PCI) are similar in case of different thrombotic risk profiles. Methods PROMETHEUS was a multicenter observational study comparing prasugrel vs. clopidogrel in ACS patients undergoing PCI. According to the 2020 ESC guidelines for non-ST elevation-ACS, patients are defined at high thrombotic risk if presenting with a clinical (diabetes mellitus requiring medication, history of recurrent myocardial infarction [MI], multivessel coronary artery disease [CAD], polyvascular [coronary and peripheral] disease, premature (<45 years) CAD, and chronic kidney disease [estimated glomerular filtration rate <60 ml/min/1.73m2]) and procedural (≥3 stents implanted, ≥3 lesions treated, total stent length >60 mm, complex revascularization [left main PCI, bifurcation or chronic total occlusion]) risk features. The primary endpoint was major adverse cardiac events (MACE), a composite of death, MI, stroke or unplanned revascularization. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated using propensity-stratified analysis to assess the effect of prasugrel vs. clopidogrel and with multivariable Cox regression to evaluate the impact of thrombotic risk. Results Among 16065 patients, 4293 were defined at high thrombotic risk and 11772 at low-to-moderate thrombotic risk. Patients treated with prasugrel had less comorbidities and risk factors than those treated with clopidogrel, both in the high and low-to-moderate thrombotic risk strata. Patients at high thrombotic risk had higher rates of both ischemic and bleeding events at 90 days and at 1 year. Patients treated with prasugrel had a lower adjusted risk of MACE at 1 year (HR 0.86, 95% CI 0.77–0.96), with no significant interaction between effect estimates and thrombotic risk. However, after stratifying the study population by the number of risk factors, there was a significant interaction for a greater reduction in MACE with prasugrel in patients with ≤1 thrombotic risk factor. Conversely, there were no differences in major bleeding among patients treated with prasugrel and clopidogrel. Conclusions Patients with ACS at high thrombotic risk who undergo PCI are at increased risk of adverse events. Prasugrel, although mainly reserved to patients with lower burden of comorbidities, reduced the risk of ischemic events both in patients at high and low-to-moderate thrombotic risk as compared with clopidogrel. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo and Eli Lilly and Company Clinical outcomes at 1 year.Impact of number of risk factors

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Clinical trials are organized for many different reasons. Most drug and device trials are designed to demonstrate the safety and efficacy of a drug or device, not to prove that they are the optimal treatments for patients. On the other hand, treatment strategy trials are designed to study the value of one therapeutic regimen compared with another when equipoise or confusion exists regarding which course to pursue. Assumptions are based on prior knowledge and opinion; in the case of coronary artery disease, most trials have been divided into those studying patients who “need” revascularization (ie, EAST [Emory Angioplasty versus Surgery Trial], BARI [Bypass Angioplasty Revascularization Investigation], CABRI [Coronary Artery Bypass Revascularization Investigation], RITA [Second Randomized Intervention Treatment of Angina], GABI [German Angioplasty Bypass Intervention], ARTS [Arterial Revascularization Therapies Study], SOS [Stent or Surgery], ERACI II [Estudio Randomizado Argentino de Angioplastia vs Cirugia II], and meta-analyses of these trails1,2⇓) and those in whom medical therapy is judged to be a reasonable choice. The latter list is short—RITA-2 [Second Randomized Intervention Treatment of Angina]3 and the awaited COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation]4 and BARI 2D [Bypass Angioplasty Revascularization Investigation 2 Diabetes]5 trials. Article p 1082 An assumption is made that patient groups can be identified that will be suitable candidates either for equipoise between 2 revascularization choices or for medical therapy versus revascularization. The study by Hueb et al6 in this issue of Circulation enrolled patients, most of whom would have been eligible for percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) trials, to 3 arms including medical therapy only. Eligible patients had multivessel coronary artery disease (3 vessels, 58%; 2 vessels, 42%), and the left anterior descending artery was involved in 92% of the patients. Therefore, these patients seem …

The American Association for Thoracic Surgery and The Society of Thoracic Surgeons reasoning for not endorsing the 2021 ACC/AHA/SCAI Coronary Revascularization Guidelines

The aim of the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study was to assess percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) as treatments for multivessel coronary artery disease in diabetic patients. CABG is generally regarded as the treatment of choice for multivessel coronary artery disease in diabetes. PCI is an alternative therapy. The Bypass Angioplasty Revascularization in Type 1 and 2 Diabetes study compared long-term outcomes of CABG with PCI in diabetic patients treated during the bare-metal stent era. We collected data prospectively on consecutive diabetic patients undergoing index angiography in a single tertiary centre from January 1998 to December 2001. Multivessel coronary artery disease was defined as more than 50% luminal stenosis in two or more vessels. Exclusion criteria included left main stem disease and previous revascularization. Two hundred and thirty-five eligible patients underwent CABG and 237 PCI. Median follow-up was 5.4 years. There were 46 (19%) deaths in the CABG group and 43 (18%) deaths in the PCI group (P = 0.64). Cox regression analysis revealed baseline glomerular filtration rate (hazard ratio 0.979, P = 0.001), age (hazard ratio 1.034, P = 0.033), urgent procedure (hazard ratio 1.97, P = 0.008) and myocardial infarction within 4 weeks (hazard ratio 2.494, P = 0.041) to be important predictors of outcome. At 5 years, there was no mortality difference (hazard ratio 1.0) following adjustment for baseline characteristics, and the Kaplan-Meier survival curves were similar. A subanalysis of patients with three-vessel disease revealed similar outcomes with both PCI and CABG. In the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study, diabetic patients with multivessel coronary artery disease had similar long-term mortality whether treated with CABG or PCI, the revascularization determined by the physician's choice. This was despite the frequent use of a strategy of selective revascularization in the PCI arm. Randomized trials comparing PCI and CABG specifically in diabetes, that is, Coronary Artery Revascularization in Diabetes and Future Revascularization Evaluation in Diabetes Mellitus: Optimal Management, will show whether drug-eluting stents further enhance PCI outcomes over the long term.

<i>Circulation</i> Editors’ Picks

A significant portion of patients with ST-elevation myocardial infarction (STEMI) display multivessel coronary artery disease. However, data on the association of multivessel coronary artery disease and reperfusion success are scarce. The aim of the current study was to analyse the impact of multivessel coronary artery disease on myocardial salvage assessed by cardiac magnetic resonance imaging in a large unselected cohort of STEMI patients. STEMI patients ( n=738) included in the AIDA STEMI trial underwent primary percutaneous coronary intervention within 12 hours after symptom onset. Cardiac magnetic resonance imaging was performed 3 days after the index event (interquartile range (IQR) 2-4). The severity of coronary artery disease was graded as single-vessel disease compared to multivessel disease. The primary endpoint was defined as a composite of death, non-fatal myocardial re-infarction and congestive heart failure (major adverse cardiac events) at 12 months. Multivessel coronary artery disease was present in 46.3% ( n=342) of all patients. Patients with multivessel coronary artery disease were older and more often had diabetes in comparison to those with single-vessel disease ( P<0.001 and P=0.005). Angiographic and electrocardiographic reperfusion success defined as Thrombolysis in Myocardial Infarction flow III post-percutaneous coronary intervention and ST-segment resolution ⩾70% were similar between both groups ( P=0.48 and P=0.21). Patients with multivessel disease displayed no significant difference with respect to myocardial salvage index (49.8 (IQR 31.4-71.6) versus 52.7 (IQR 35.1-67.1), P=0.81) in comparison to patients with single-vessel disease. The presence of multivessel coronary artery disease was identified as an independent predictor for the time-dependent occurrence of major adverse cardiac events (hazard ratio 3.25, 95% confidence interval 1.53-6.91, P=0.002). Although multivessel coronary artery disease is not associated with impaired reperfusion success assessed by cardiac magnetic resonance imaging, patients with multivessel disease are at a high risk of adverse clinical outcomes. Clinicaltrials.gov NCT00712101.

Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease–2

Consumers' price related response in the clothing purchase decision-making process includes their expectation of price, price perception, attitude toward price and consequent behaviors. The purposes of this research are to systematically organize consumers' price related responses in the clothing purchase decision-making process, and to explain the effect of price on their purchasing. The qualitative research including shopping observation and in-depth interview was conducted. The result identified stages that showed different price related responses in clothing purchase decision-making process, and clarified each stage's characteristics. In the internal search stage, consumers recalled price information from memory and had a specific expectation about the price. This set a direction for the external search. In the external search stage, consumers selected brands or stores by a non-compensatory evaluating with an expectation of the price, and narrowed these down to several determinant alternatives by actively evaluating the products. In case a sufficient amount of price information was not recalled, the consumer established reference price through the external search. Finally, in the purchasing stage, consumers evaluated the determinant alternatives based on their compensatory evaluation. When perception of price was negative, consumers evaluate price combined with the higher criteria of clothing benefits, such as symbolic value and usability. The research is expected to contribute to predicting consumers' responses to price, and to establishing an effective pricing strategy.

Submit Manuscript | http://medcraveonline.com The study of Hachamovitch et al. [3] emphasized the relationship between inducible ischemia on SPECT and the presence of shortterm survival benefits with early revascularization vs. medical therapy.Revascularization was associated with a reduction in mortality for patients having moderate to severe ischemia. The cut-off level of ischemic myocardium, assessed by summed stress scores, to predict lower mortality using revascularization was approximately 10-12.5% [3]. Kim et al. [4] supported the benefit of ischemia-guided revascularization with myocardial perfusion imaging for patients with multivessel coronary artery disease. The outcomes of ischemia-guided revascularization were retrospectively compared with those of non ischemiaguided revascularization in a registry of 5,340 patients with multivessel coronary disease comprising 2,587 percutaneous coronary interventions (PCIs) with drug-eluting stents and 2,753 coronary artery bypass graft (CABG) surgeries. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was significantly lower in the ischemia-guided than in the non ischemia-guided group, primarily driven by the lower repeat revascularization rate. Subgroup analysis showed that ischemiaguided reduced the risk of MACCE in PCI but not in CABG patients [4]. Several diagnostic modalities are available for use as tools to establish the initial diagnosis, assess disease severity, and select the appropriate treatment strategy in symptomatic patients suspected of having SCAD. In relation to this point, a multicenter study performed in Japan hypothesise that the choice of the initial diagnostic test might influence the treatment strategy. They showed that patients receiving initial SPECT had a lower rate of revascularization than those receiving coronary angiography [5]. In relation to invasive methods assessing ischemia, fractional flow reserve (FFR) is considered nowadays the elective way for invasive assessment of physiological stenosis significance and a decisive tool for decision making in coronary revascularization. The recently published ESC guidelines on the management of stable coronary artery disease endorse the use of FFR for risk stratification. FFR is calculated as the ratio of distal coronary pressure to aortic pressure measured during maximal hyperaemia. A normal value for FFR is 1.0. Stenoses with a FFR >0.80 are hardly ever associated with exercise-induced ischaemia [6]. The principal utility of FFR is in certain situations when it is not clear whether an intermediate angiographic lesion causes ischemia. The use of FFR in the catheterization laboratory accurately identifies which lesions should be revascularized and improves the outcome in most elective clinical and angiographic conditions, as compared with the situation where revascularization decisions are simply made on the basis of angiographic appearance of the lesion [7]. The DEFER study evaluated the 5-year outcomes in 325 patients assigned to 3 groups: deferred group (FFR ≥0.75 without PCI), PCI group (FFR ≥0.75 with PCI), and a control group (FFR <0.75 with PCI). 5-year event-free survival rates were similar in the deferred and PCI groups, with a risk of cardiac death or MI in patients with normal FFR inferior to 1% per year [8]. FAME study evaluated angio-guided versus FFR-guided percutaneous revascularization in patients with multivessel disease. Routine measurement of FFR in patients with multivessel coronary artery disease who were undergoing PCI with drug-eluting stents significantly reduced the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at one year of follow up [9]. The 2-year outcome report of the FAME study supported the safety of deferring PCI for non ischemic lesions [10]. Of interest, a sub analysis of the FAME study also showed that angiography is inaccurate in assessing the functional significance of a coronary stenosis when compared with the FFR in the 50% to 70% category but also in the 70% to 90% angiographic severity category [11]. The FAME-2 trial tested the benefits, for SCAD, of FFR-guided PCI plus optimal medical therapy with optimal medical treatment alone. PCI group had significant lower rate of primary endpoint event: death, MI, or urgent revascularization. Also there was a lower rate of urgent revascularization in the PCI group than in the medical therapy group [12].

In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease. Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7-4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25-0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively. In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.