Adverse Ischemic Events Research Articles

New Possibilities of Antithrombotic Therapy of Patients with Peripheral and Widespread Atherosclerotic Lesion

Atherosclerotic peripheral artery disease (PAD) is well-known thrombotic risk factor in different cohorts of patients. This current review analyzes epidemiological data of trials and registries about influence both clinical and asymptomatic peripheral atherosclerotic disease on adverse ischemic events. Individual assessment of the atherothrombotic prevalence, which is directly related to vascular thrombotic risk, remains an important problem. Issue of PAD routine screening using traditional methods of ultrasound duplex scanning, measurement of ankle-brachial index is discussed in details. Comparative efficiency of present antiplatelet and anticoagulant drugs is shown in the key of preventing PAD thrombotic complications. PAD detection can be the reason for intensification of antithrombotic treatment, the only one option of which until recently was an additional treatment with P2Y12 platelet receptors blockers. However, the routine treatment with dual antiplatelet therapy in stable manifestations of atherothrombosis is not supported by the current guidelines. In this regard, it seems relevant to intensify therapy by simultaneously affecting on the platelet and plasma components of hemostasis in patients with PAD, that was demonstrated in a recently published study COMPASS. Treatment with rivaroxaban small doses in addition to acetylsalicylic acid allowed to improve significantly outcomes in a wide range of patients with stable manifestations of atherothrombosis without high risk of bleeding and severe renal impairment. However, use of this multicomponent therapy has not been approved by relevant clinical recommendations yet, which causes certain difficulties in choosing optimal scheme of antithrombotic treatment among patients with PAD.

Elective Coronary Revascularization Procedures in Patients With Stable Coronary Artery Disease: Incidence, Determinants, and Outcome (From the CORONOR Study)

ObjectivesThe authors sought to describe the incidence, determinants, and outcome of elective coronary revascularization (ECR) in patients with stable coronary artery disease (CAD). BackgroundObservational data are lacking regarding the practice of ECR in patients with stable CAD receiving modern secondary prevention. MethodsThe authors analyzed coronary revascularization procedures performed during a 5-year follow-up in 4,094 stable CAD outpatients included in the prospective multicenter CORONOR (Suivi d'une cohorte de patients COROnariens stables en région NORd-Pas-de-Calais) registry. ResultsSecondary prevention medications were widely prescribed at inclusion (antiplatelet agents 96.4%, statins 92.2%, renin-angiotensin system antagonists 81.8%). A total of 481 patients underwent ≥1 coronary revascularization procedure (5-year cumulative incidences of 3.6% [0.7% per year] for acute revascularizations and 8.9% [1.8% per year] for ECR); there were 677 deaths during the same period. Seven baseline variables were independently associated with ECR: prior coronary stent implantation (p < 0.0001), absence of prior myocardial infarction (p < 0.0001), higher low-density lipoprotein cholesterol (p < 0.0001), lower age (p < 0.0001), multivessel CAD (p = 0.003), diabetes mellitus (p = 0.005), and absence of treatment with renin-angiotensin system antagonists (p = 0.020). Main indications for ECR were angina associated with a positive stress test (31%), silent ischemia (31%), and angina alone (25%). The use of ECR had no impact on the subsequent risk of death, myocardial infarction, or ischemic stroke (hazard ratio: 1.04; 95% confidence interval: 0.76 to 1.41). ConclusionsThese real-life data show that ECR is performed at a rate of 1.8% per year in stable CAD patients widely treated by secondary medical prevention. ECR procedures performed in patients without noninvasive stress tests are not rare. Having an ECR was not associated with the risk of ischemic adverse events.

Optimal pharmacological therapy in ST-elevation myocardial infarction-areview : Areview of antithrombotic therapies in STEMI.

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.

Abstract TP84: Safety and Effectiveness of Ticagrelor in Patients With Clopidogrel Resistance Undergoing Angioplasty, Stent or Flow Diverter Placement

Background and Purpose: Nearly 30% of the patients have clopidogrel resistance and are at high risk for in-stent thrombosis and adverse ischemic events. Ticagrelor is an allosteric platelet antagonist that reversibly inhibits the P2Y12 platelet receptor more potently than clopidogrel. We report upon the safety and effectiveness of ticagrelor in patients with cerebrovascular diseases and clopidogrel resistance undergoing angioplasty and/or stent or flow diverter placement. Methods: We analyzed data from our prospectively maintained endovascular database and identified patients treated with ticagrelor and underwent treatment with a stent or flow diverter. The patients were divided into an acutely loaded dose group and those converted from clopidogrel due to clopidogrel resistance, defined by platelet aggregation value of 200 PRU VerifyNow P2Y12 test. Patients received standard dual antiplatelet therapy, however, despite repeat clopidogrel loading doses, were found to be clopidogrel non-responders and were then administered ticagrelor 180mg loading dose and maintained on 90mg BID dosing. We ascertained occurrence of any bleeding complications, classified as major (hgb decrease &gt;5 g/dl), minor (hgb decrease 3-5 g/dl), or insignificant. Results: A total of 36 (13.8%) patients (mean age 64.7±13.8 years; 58.3% females) had clopidogrel resistance out of 260 patients screened. Of those, 29 patients were switched from clopidogrel to ticagrelor due to an elevated PRU (avg 294.76±41.32 PRU) and 7 patients without previous antiplatelet use received a bolus and maintenance dose. Only one patient experienced a transient ischemic event within 24 hours after starting ticagrelor. Patients who were acutely loaded did not experience any ischemic events. No patient experienced symptomatic or asymptomatic hemorrhage on ticagrelor in the post-op period. A total of 43 procedures were performed in 36 patients with clopidogrel resistance: 26 pipeline placements, 8 wingspan stent placements, 2 LVIS stents, 1 neuroform stent with pipeline, and 7 angioplasties. Conclusions: Our study demonstrates the safety and effectiveness of loading or switching patients to ticagrelor with cerebrovascular diseases undergoing angioplasty, stent or flow diverter placement.

Males With Rheumatoid Arthritis Often Evidence Carotid Atheromas on Panoramic Imaging: A Risk Indicator of Future Cardiovascular Events

Males with rheumatoid arthritis (RA) are at an exceedingly high risk of adverse intraoperative ischemic events, given the role of systemic inflammation in the atherogenic process. We hypothesized that their panoramic images would demonstrate calcified carotid artery atheromas (CCAPs) significantly more often than those from a general population of similarly aged men. We implemented a retrospective observational study. The sample was composed of male patients older than 55years of age who had undergone panoramic imaging studies. The predictor variable was the diagnosis of RA confirmed by a positive rheumatoid factor (RF) titer, and the outcome variable was the prevalence rate of CCAPs. The other major study variable was the level of RF among the patients evidencing CCAPs. The prevalence of CCAPs among the patients with RA was then compared with that of a historical general population of similarly aged men. Descriptive and bivariate statistics were computed, and the P value was set at .05. Of the 100 men (mean age 69.89±8.927years) with RA, 29 (29%; mean age 72.10±7.68years) had atheromas (CCAP+). Of these 29 men, 25 (86%; mean age 71.88±7.43years) had a RF titer of ≥41 IU/mL, twice that of normal. A statistically significant (P<.05) association was found between a diagnosis of RA and the presence of an atheroma on the panoramic image compared with the 3% rate found in the historical cohort. The results of the present study suggest that CCAP, a risk indicator of future adverse cardiovascular events, is frequently seen on panoramic images of male patients with RA and that these individuals routinely manifest high titer levels of RF, a biologic marker of inflammation. Oral and maxillofacial surgeons planning surgery for male patients with RA must be uniquely vigilant for the presence of these lesions.

Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation

Background and aimsTarget lesion restenosis is the most frequent complication after angioplasty and stenting for peripheral artery disease (PAD). MicroRNAs (miRs) regulate crucial pathophysiological processes leading to in-stent restenosis and thrombosis. The aim of this study was to investigate the predictive value of 11 miRs for the composite endpoint of target lesion restenosis and atherothrombotic events (primary endpoint), and target vessel revascularization (TVR, secondary endpoint) in 62 consecutive PAD patients after infrainguinal angioplasty with stent implantation. MethodsCirculating miRs were assessed using quantitative real-time polymerase chain reactions. ResultsWithin the 2 years of follow-up, the primary endpoint occurred in 26 patients (41.9%), and 21 patients (33.9%) underwent TVR. miR-92a and miR-195 were identified as independent predictors of the primary endpoint after adjustment for age, sex and clinical risk factors with respective HR per 1 increase of standard deviation (1-SD) of 0.55 (95% CI: 0.34–0.88, p = 0.013) and HR per 1-SD of 0.40 (95% CI: 0.23–0.68, p = 0.001). MiR-195 independently predicted TVR with HR per 1-SD of 0.40 (95% CI: 0.22–0.75, p = 0.005). Adding miR-195 to clinical risk factors improved Harrell's C-index to 0.75 (95% CI: 0.66–0.85, p = 0.03) and was superior to a model with miR-92a (C-index: 0.70, 95% CI: 0.60–0.80, p for comparison =0 .012). Assessment of both miR-92a and miR-195 had no incremental value when compared to miR-195 alone (C-index: 0.79, 95% CI: 0.69–0.88, p = 0.313). ConclusionsCirculating miR-195 predicts adverse ischemic events and TVR after infrainguinal angioplasty with stent implantation. MiR-195 could improve risk stratification after peripheral endovascular revascularizations.

Percutaneous coronary intervention of lesions with in-stent restenosis: A report from the ADAPT-DES study

There is a paucity of data from large contemporary cohorts of patients with in-stent restenosis (ISR) treated with drug-eluting stents (DESs), and no studies have examined the impact of high platelet reactivity (HPR) on the occurrence of ischemic events after ISR percutaneous coronary intervention (PCI) with DESs. We sought to report outcomes after PCI of ISR lesions and its association with HPR. Patients in the prospective, multicenter ADAPT-DES study were stratified according to whether they had ISR versus non-ISR PCI. Two-year outcomes were compared between the groups using Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; target vessel failure (TVF) was defined as the composite of all-cause death, myocardial infarction, or ischemia-driven target vessel revascularization. Among the 8,582 patients included in the ADAPT-DES study, 840 (9.8%) patients underwent successful ISR PCI. ISR PCI was independently associated with a higher 2-year risk of TVF (adjusted hazard ratio [HR] 1.95; 95% CI 1.68-2.27; P<.001) and stent thrombosis (adjusted HR 1.95; 95% CI 1.08-3.51; P=.027) but not bleeding (adjusted HR 0.94; 95% CI 0.73-1.21; P=.64). There was no statistical interaction between HPR and ISR versus non-ISR PCI in regard to TVF (adjusted Pinteraction=.81). ISR PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in ISR and non-ISR PCI. More effective therapeutic strategies for managing ISR lesions are necessary.

The quest for safer antithrombotic treatment regimens in patients with coronary artery disease: new strategies and paradigm shifts

ABSTRACTIntroduction: Despite the undeniable benefits on reducing ischemic adverse events, antiplatelet regimens including dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor inhibitors are associated with an increased risk of bleeding. The awareness of the unfavorable prognostic implications associated with bleeding complications have somewhat hampered the enthusiasm towards the use of more potent antiplatelet treatment regimens or prolonged use of DAPT. This awareness also has prompted a series of investigations geared towards the identification of antithrombotic treatment regimens which are efficacious at reducing ischemic recurrences while also safe in terms of bleeding risk profile.Areas covered: The present manuscript focuses on new approaches for improving the safety profile of antithrombotic treatment regimens, including most recent updates from clinical trials, as well as future perspectives in the field.Expert commentary: Results of ongoing trials testing new antithrombotic treatment regimens, including new drugs, new combinations, which may be used for different duration of time according to the individual’s risk of thrombotic and bleeding complications, may lead to paradigm shifts in secondary prevention of atherothrombotic events in patients with coronary artery disease.

Impact of Pre-Diabetes on Coronary Plaque Composition and Clinical Outcome in Patients With Acute Coronary Syndromes: An Analysis From the PROSPECT Study

ObjectivesThe aim of this study was to investigate the impact of pre-diabetes (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients with acute coronary syndromes (ACS). BackgroundPre-DM (i.e., the early stages of glucometabolic disturbance) is common among patients with ACS, but the extent to which pre-DM influences coronary plaque characteristics and the risk for adverse ischemic events is unclear. MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in Coronary Tree) study, patients with ACS underwent quantitative coronary angiography, grayscale intravascular ultrasound, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention. Patients were divided into 3 groups according to their glucometabolic status, as defined by the American Diabetes Association: normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups were compared with regard to coronary plaque characteristics and the risk for major adverse cardiac events (MACEs) (defined as cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina). ResultsAmong 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183 (33.4%) had DM. There were no significant differences between the groups with regard to intravascular ultrasound findings indicative of vulnerable plaques. Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20; 95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio: 1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with increased risk for MACEs. ConclusionsImpaired glucose metabolism is common among patients presenting with ACS. DM but not pre-DM is associated with an increased risk for MACEs. Thus, preventing patients from progressing from pre-DM to DM is important. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466)

Percutaneous coronary intervention of bifurcation lesions and platelet reactivity.

Although bifurcation percutaneous coronary intervention (PCI) is associated with lower procedural success rates and higher risk of complications, there are little data regarding outcomes after successful bifurcation PCI with contemporary stents and techniques. Whether residual platelet reactivity (PR) affects outcomes differently after bifurcation versus non-bifurcation PCI is also unknown. We studied the association between bifurcation PCI, PR, and clinical outcomes among patients undergoing successful PCI with drug-eluting stents. Patients in the prospective, multicenter ADAPT-DES study were stratified according to whether they underwent bifurcation PCI. Two-year outcomes were compared between groups using Cox proportional hazards models. Target vessel failure (TVF) was defined as the composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization. Among the 8582 patients included in ADAPT-DES, 1276 (15%) had bifurcation PCI. Bifurcation PCI was independently associated with increased risk of TVF (adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08-1.46, p=0.003), driven by higher risk of myocardial infarction (5.9% vs. 4.6%, p=0.033) and ischemia-driven target vessel revascularization (13.0% vs. 9.2%, p<0.0001). There was no statistical interaction between PR and bifurcation PCI regarding TVF risk (adjusted pinteraction=0.87). Stenting of both bifurcation branches was associated with the highest risk of TVF (adjusted HR 1.91, 95% CI 1.48-2.46 versus non-bifurcation PCI; ptrend<0.001). Bifurcation PCI is associated with a higher risk of 2-year adverse ischemic events than non-bifurcation PCI, a risk that is particularly high when both bifurcation branches are stented, and with HPR conferring similar risk for bifurcation and non-bifurcation PCI.

TCT-724 Impact of Coronary Calcification Severity on Clinical Outcomes After Contemporary PCI – Insights From the CHAMPION PHOENIX Trial

Percutaneous coronary intervention (PCI) of calcified lesions has been associated with an increased risk of adverse ischemic events. The importance of coronary artery calcification (CAC) severity and its association with outcomes has not been clearly studied in a large, contemporary cohort. We

Benefits and risks of P2Y12 inhibitor preloading in patients with acute coronary syndrome and stable angina.

Treatment with P2Y12 inhibitors is an integral part of the standard of care for patients undergoing percutaneous coronary intervention. However, the most appropriate timing for P2Y12 inhibitor administration remains unclear, and the value of "preloading" with P2Y12 inhibitors prior to cardiac catheterization is controversial. While pre-catheterization treatment with P2Y12 inhibitors is performed with the goal of decreasing adverse cardiovascular events, this potential benefit must be weighed against the increased risk of bleeding complications and operative delay if coronary artery bypass graft surgery is indicated. A number of studies have been conducted to evaluate the utility of preloading with P2Y12 inhibitors prior to cardiac catheterization for varying indications including stable angina and acute coronary syndrome (ACS). In this article, we review the literature and discuss the advantages and disadvantages of the preloading strategy. Several individual studies offer inconclusive and even conflicting findings. However, when taken in sum, these studies allow for several conclusions about the utility of P2Y12 inhibitor pretreatment. The existing literature demonstrate that preloading is associated with some degree of reduction in adverse ischemic events, although this benefit comes with an increased risk of bleeding complications. The appropriateness of preloading therefore varies based on the indication for catheterization, likely justified in patients with ACS but unlikely to benefit patients with stable angina.

Platelet aggregation and the risk of stent thrombosis or bleeding in elective percutaneous coronary intervention patients.

: Platelet aggregation monitoring in patients after stent implantation is a promising way of preventing stent thrombosis and bleeding. The aim of the study was to verify whether clopidogrel (ADPtest) and aspirin (ASPItest) response measured by Multiplate (Dynabyte, Munich, Germany) analyzer in elective percutaneous coronary implantation patients predict the risk of stent thrombosis or other ischemic adverse events and bleeding. In this prospective, observational study 697 elective percutaneous coronary implantation patients were analyzed. The median ASPItest was 86 AU min. In 69 patients (9.9%), an ASPI result of more than 203 AU min was observed. The median ADP-dependent platelet aggregation was 212 AU min. In 36 (5.2%) patients, the result was at least 468 AU min. Cox regression analysis showed the prognostic factors of definite or probable stent thrombosis and cardiac death at 1 year were higher ASPItest result [odds ratio (OR) 1.006, 95% confidence interval (CI) 1.004-1.008, P < 0.001], ASPItest more than 203 AU min (OR 7.61, 95% CI 2.83-20.43, P < 0.001), higher ADPtest result (OR 1.005, 95% CI 1.003-1.007, P < 0.001) and ADPtest at least 468 AU min (OR 12.54, 95% CI 4.56-35.53, P < 0.001). In turn, ADPtest 188 AU min or less predicted GUSTO scale major and moderate bleeding (OR 4.15, 95% CI 1.12-15.32, P = 0.033). There was also a strong trend toward higher rate of major and moderate bleeding for the ASPItest less than 35 AU min (lowest quintile) - (OR 3.04, 95% CI 0.96-9.58, P = 0.058). Lower creatinine clearance and lower hemoglobin level were associated with both ischemic and bleeding complications. The results of this study show that impaired platelet response to clopidogrel and aspirin measured by the Multiplate analyzer results in increased risk of stent thrombosis and cardiac death. Furthermore, the study showed that increased response to clopidogrel is related to major and moderate bleeding events.

Percutaneous Coronary Intervention of Saphenous Vein Graft.

Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) has historically been associated with a high risk of adverse ischemic events, but there is a paucity of contemporary data on the second-generation drug-eluting stent use within SVG, and the relative importance of high platelet reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied ischemic and bleeding events after SVG PCI and their association with HPR. Subjects in the prospective, multicenter ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two-year outcomes were compared between groups using univariate and multivariable Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; major adverse cardiac events were defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG PCI was independently associated with a higher 2-year risk of major adverse cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69-3.23; P<0.0001), ischemia-driven target vessel revascularization (adjusted hazard ratio, 1.82; 95% confidence interval, 1.37-2.42; P<0.0001), and stent thrombosis (adjusted hazard ratio, 2.26; 95% confidence interval, 1.42-3.59; P=0.0006), but not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68-1.46; P=0.97). There was no statistical interaction between HPR and SVG PCI in regard to major adverse cardiac events (adjusted Pinteraction=0.99). SVG PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual Antiplatelet Therapy

Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggregation after platelet stimulation with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel (group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent elective angioplasty and stenting, whereas all patients included in groups 2 and 3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent PCI. Significant differences between maximal and final platelet aggregation were observed with all agonists throughout the groups (all p<0.001). Disaggregation was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP (clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel-treated patients, and after platelet stimulation with collagen and epinephrine in prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet activation that are not inhibited by standard antiplatelet therapy allow persisting platelet aggregation and may at least in part be responsible for adverse ischemic events.

Meta-Analysis of Randomized Controlled Trials of Percutaneous Coronary Intervention With Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease

Few randomized controlled trials (RCTs) and observational studies had shown acceptable short-term efficacy and safety of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) compared with coronary artery bypass grafting (CABG) in selected patients with left main coronary artery disease (LMCAD). We aimed to evaluate long-term outcomes of PCI using DES compared with CABG in patients with LMCAD. On November 1, 2016, we searched available databases for published RCTs directly comparing DES PCI with CABG in patients with LMCAD. Odds ratios (ORs) were used as the metric of choice for treatment effects using a random-effects model. I-squared index was used to assess heterogeneity across trials. Prespecified end points were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, and repeat revascularization at maximal available follow-up. We identified 5 RCTs including a total of 4,595 patients, with a median follow-up of 60months. The risk of all-cause mortality (OR 1.01; 95% confidence interval [CI] 0.76 to 1.34) and cardiovascular mortality (OR 1.02; 95% CI 0.73 to 1.42) were comparable between PCI with DES and CABG. Similarly, there were no statistically significant differences between PCI with DES and CABG for MI (OR 1.45; 95% CI 0.87 to 2.40) and stroke (OR 0.87; 95% CI 0.38 to 1.98). Conversely, repeat revascularization was significantly higher with PCI compared with CABG (OR 1.82; 95% CI 1.51 to 2.21). In conclusion, in patients with LMCAD, PCI with DES appears to be a viable alternative to CABG at long-term follow-up, with similar risks of ischemic adverse events (mortality, MI, and stroke) but a higher risk of repeat revascularization.

Antithrombotic therapy for patients with STEMI undergoing primary PCI.

Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Intravenous anticoagulant drugs available for PPCI include the indirect thrombin inhibitors unfractionated heparin and low-molecular-weight heparin, and the direct thrombin inhibitor bivalirudin. Intravenous antiplatelet drugs mainly include glycoprotein IIb/IIIa inhibitors and the P2Y12-receptor inhibitor cangrelor. Dual antiplatelet therapy with aspirin and an oral P2Y12-receptor inhibitor is pivotal for the acute and long-term treatment of patients with STEMI undergoing PPCI. Prasugrel and ticagrelor provide a more prompt, potent, and predictable antiplatelet effect compared with clopidogrel, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in PPCI. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. Thrombin has an important role, suggesting the need for strategies directly targeting circulating thrombin or other factors of the coagulation cascade, such as oral anticoagulants (rivaroxaban), and the thrombin receptor on the platelet membrane (vorapaxar). In this Review, we provide an overview of currently available antithrombotic therapies used in patients with STEMI undergoing PPCI, results from pivotal clinical trials and their implications for guidelines, as well as recommendations for clinical practice.

Safety of Intra-Arterial Injection with Tumor-Activated T Cells to the Rabbit Brain Evaluated by MRI and SPECT/CT

Glioblastoma multiforme (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical, radiotherapy, and surgical therapy. A continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TILs) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intraarterial injection of TILs as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor. Prior to clinical trials of intra-arterial injections with any cells, preclinical safety data with special emphasis on embolic–ischemic events are necessary to obtain. We used native rabbits as a model for intra-arterial injections with routine clinical catheter material and a clinical angiography suite. We selectively infused a total dose of 20 million activated T cells at a cell concentration of 4,000 cells/ml over 8 min of injection time. The rabbits were evaluated for ischemic lesions by 9.4 T magnetic resonance imaging (MRI) (n = 6), and for tracking of injected cells, single-photon emission computed tomography/computed tomography (SPECT/CT) was used (n = 2). In this study, we show that we can selectively infuse activated T cells to a CNS volume of 3.5 cm3 (estimated from the volumetric MRI) without catastrophic embolic– ischemic adverse events. We had one adverse event with a limited basal ganglia infarction, probably due to catheter-induced mechanical occlusion of one of the lateral lenticulostriatal arteries. The cells pass through the native brain without leaving SPECT signals. The cells then, over the first hours, end up in the liver to a large extent and to a lesser degree by the spleen, pancreas, and kidneys. Virtually no uptake could be detected in the lungs. This indicates a difference in biodistribution as opposed to other cell types when infused intravenously.

Orbital atherectomy for treating de novo , severely calcified coronary lesions: 3-year results of the pivotal ORBIT II trial

The presence of heavy coronary artery calcification increases the complexity of percutaneous coronary intervention (PCI) and increases the incidence of major adverse cardiac events (MACE): death, myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis. The ORBIT II (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) trial reported low rates of procedural, 30-day, 1-year, and 2-year ischemic complications after treatment of de novo, severely calcified lesions with the Diamondback 360° Coronary Orbital Atherectomy System (OAS) (Cardiovascular Systems, Inc.). ORBIT II was a single-arm trial that enrolled 443 patients at 49U.S. sites; in this study, de novo, severely calcified coronary lesions were treated with OAS prior to stenting. The primary safety endpoint was 30-day MACE: the composite of cardiac death, MI, and TVR (inclusive of target lesion revascularization (TLR)). The primary efficacy endpoint was procedural success: stent delivery with a residual stenosis of <50% without the occurrence of in-hospital MACE.The present analysis reports the final, 3-year follow-up results from ORBIT II. The majority of subjects (88.2%) underwent PCI with drug-eluting stents after orbital atherectomy. There were 360 (81.3%) subjects who completed the protocol-mandated 3-year visit.The overall cumulative rate of 3-year MACE was 23.5%, including cardiac death (6.7%), MI (11.2%), and TVR (10.2%). The 3-year target lesion revascularization rate was 7.8%. In the final 3-year analysis of the ORBIT II trial, orbital atherectomy of severely calcified coronary lesions followed by stenting resulted in a low rate of adverse ischemic events compared with historical controls.Orbital atherectomy represents a safe and effective revascularization strategy for patients with severely calcified coronary lesions. The ORBIT II trial enrolled 443 subjects to study orbital atherectomy followed by stenting for de novo severely calcified coronary lesions. The overall cumulative 3-year MACE rate was 23.5%, including cardiac death (6.7%), MI (11.2%), and TVR (10.2%); the 3-year target lesion revascularization rate was 7.8%. Orbital atherectomy of heavily calcified coronary lesions followed by stenting results in a low rate of adverse ischemic events compared with historical controls; it represents a reasonable revascularization strategy for patients with severely calcified coronary lesions.

Impact of completeness of revascularization in complex coronary artery disease as measured with the SYNTAX revascularization index: An SEEDS Substudy

We sought to study whether the level of completeness of revascularization as measured by the SYNTAX revascularization index (SRI) independently predicts adverse ischemic events after percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES). The SRI quantifies the proportion of revascularized myocardium. It has been shown to independently predict adverse ischemic events after PCI with first-generation DES. Among 1,900 patients enrolled in a registry to evaluate safety and effectiveness of everolimus drug-eluting stent (SEEDS) for coronary revascularization, the SRI was calculated and available for 1,851 patients. The patients were stratified into three groups according to the degree of revascularization (SRI = 100% [complete revascularization], SRI = 50 to <100%, and SRI <50%). Two-year mortality and major adverse cardiac events (MACE) were compared between the groups. The SRI ranged from 4-100%, with a mean of 85.4%. Complete revascularization was achieved in 1,190 patients, while the SRI was 50% to <100% in 472 patients and <50% in 189 patients. Two-year mortality and MACE rates were higher in patients with lower SRI. ROC analysis showed an optimal SRI cutoff of 85% for predicting the 2-year mortality risk. An SRI ≥85% was associated with a similar risk of death to complete revascularization. The SRI independently predicted 2-year mortality and MACE. The SRI predicts mortality and adverse ischemic events in patients with complex CAD who underwent contemporary PCI with second-generation DES. Revascularizing ≥85% of the CAD burden was associated with a good prognosis and should be considered as a reasonable goal. © 2017 Wiley Periodicals, Inc.