Search

The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator.In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared.Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All-cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity.Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses.In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile.

The purpose of this study was to assess the extent to which the association between premature dual antiplatelet therapy (DAPT) discontinuation and excess risk of thrombotic events varies according to the reason and timing of DAPT discontinuation and whether high on-treatment platelet reactivity (HPR) influences the risk of thrombotic events after premature DAPT discontinuation.DAPT after percutaneous coronary intervention (PCI) suppresses platelet reactivity, and HPR on clopidogrel after PCI is associated with an increased risk of thrombotic events.ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients successfully treated with coronary drug-eluting stents that assessed HPR on clopidogrel. For patients who discontinued aspirin or clopidogrel at any time during the study, the reasons for discontinuation were systematically categorized.Planned DAPT discontinuation occurred within 2 years in 3,203 (37.3%) patients. One thousand four hundred eighteen (16.5%) patients discontinued DAPT for unplanned reasons, including surgery or trauma (n = 768 [8.9%]), patient nonadherence (n = 321 [3.7%]), bleeding complications (n = 264 [3.1%]), and drug allergy or hypersensitivity (n = 113 [1.3%]). Unplanned but not planned DAPT discontinuation was associated with an increased risk of a major adverse cardiac event (MACE, defined as the composite of cardiac death, myocardial infarction, or stent thrombosis); with highest risk within 3 months after PCI (adjusted HR: 7.65, 95% CI: 2.77-21.10 vs adjusted HR: 2.47, 95% CI: 1.70-3.58 for unplanned DAPT discontinuation ≥3 weeks after PCI). MACE risk after DAPT discontinuation was not moderated by HPR (PIn this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794).

The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention.Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated.In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization.A total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; PTicagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD).The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined.The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with ≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of0.5 mg/dL or a relative increase of ≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate 60 mL/min/1.73 mOf 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted HR: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95% CI: 1.22-2.55; MI, HR: 1.67; 95% CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95% CI: 1.10-2.65; and major bleeding, HR: 1.38; 95% CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95% CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95% CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95% CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95% CI: 1.65-4.31) groups were at higher risk of NACE.CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

The aim of this study was to determine the prevalence and prognostic impact of high bleeding risk (HBR), as determined by the Academic Research Consortium HBR criteria, in real-world patients undergoing left main (LM) percutaneous coronary intervention (PCI).LM PCI is often reserved for patients at increased risk for periprocedural adverse events. Patients at HBR represent a relevant percentage of this cohort, but their outcomes after LM PCI are still poorly investigated.All patients undergoing LM PCI between 2014 and 2017 at a tertiary care center were prospectively enrolled. Patients were defined as having HBR if they met at least 1 major or 2 minor Academic Research Consortium HBR criteria. The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stroke at 12 months.Among 619 enrolled patients, 55.3% were at HBR. The rate of the primary endpoint was 4-fold higher in patients at HBR compared with those without HBR (20.5% vs 4.9%; HR: 4.43; 95% CI: 2.31-8.48), driven by an increased risk for all-cause death (HR: 3.88; 95% CI: 1.88-8.02) and MI (HR: 6.18; 95% CI: 1.83-20.9). Rates of target vessel or lesion revascularization and stent thrombosis were comparable in the 2 groups. Bleeding occurred more frequently in patients at HBR (HR: 3.77; 95% CI: 1.83-7.76). Consistent findings were observed after Cox multivariable regression adjustment.Among patients undergoing LM PCI, those with HBR are at increased risk for all-cause death, MI, and bleeding. Conversely, rates of repeat revascularization and stent thrombosis were comparable, suggesting frailty and comorbidities as primary causes of worse outcomes in patients at HBR.

The aim of this study was to determine the risk period for increased stent thrombosis (ST) after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and whether this increased risk is related to high platelet reactivity (HPR).ST risk after PCI is higher among patients with ACS than those with stable ischemic heart disease. When ST risk is highest in patients with ACS and how that is affected by HPR is unknown.Using the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry, ST rates during 2-year follow-up post-PCI with drug-eluting stents were compared among patients presenting with ACS (myocardial infarction [MI] or unstable angina) or stable ischemic heart disease (non-ACS). Landmark analyses were done at 30 days and 1 year post-PCI. Platelet reactivity on aspirin and clopidogrel post-PCI was assessed using VerifyNow assays.Of 8,582 patients, 2,063 presented with MI, 2,370 with unstable angina, and 4,149 with non-ACS. Incidence rates of HPR were 48.0%, 43.3%, and 39.8%, respectively (p 0.001). Within the first 30 days post-PCI, patients presenting with MI had increased ST risk compared with patients with non-ACS (hazard ratio [HR]: 4.52; 95% confidence interval [CI]: 2.01 to 10.14; p 0.001). After 30 days, relative ST risks were progressively lower and no longer significant between groups (31 days to 1 year post-PCI: HR: 1.97; 95% CI: 0.80 to 4.85;1 year post-PCI: HR: 0.89; 95% CI: 0.27 to 2.92). The elevated ST risk in patients with MI within 30 days was largely confined to those with HPR on clopidogrel (HR: 5.77; 95% CI: 2.13 to 15.63; p 0.001).Among patients undergoing PCI, rates of ST during 2-year follow-up were highest in those with MI and lowest in those with non-ACS. Increased ST risk in patients with MI was greatest in the first 30 days post-PCI and was observed predominantly among those with increased HPR on clopidogrel. These findings emphasize the importance of adequate P2Y

The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.The role of abbreviated DAPT followed by an oral P2YTwo randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar.Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

The aim of this study was to assess race-based differences in patients undergoing percutaneous coronary intervention from a large pooled database of randomized controlled trials.Data on race-based outcomes after percutaneous coronary intervention are limited, deriving mainly from registries and single-center studies.Baseline characteristics and outcomes at 30 days, 1 year, and 5 years were assessed across different races, from an individual patient data pooled analysis from 10 randomized trials. Endpoints of interest included death, myocardial infarction, and major adverse cardiac events (defined as cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization). Multivariate Cox proportional hazards regression was performed to assess associations between race and outcomes, controlling for differences in 12 baseline covariates.Among 22,638 patients, 20,585 (90.9%) were white, 918 (4.1%) were black, 404 (1.8%) were Asian, and 473 (2.1%) were Hispanic. Baseline and angiographic characteristics differed among groups. Five-year major adverse cardiac event rates were 18.8% in white patients (reference group), compared with 23.9% in black patients (p = 0.0009), 11.2% in Asian patients (p = 0.0007), and 21.5% in Hispanic patients (p = 0.07). Multivariate analysis demonstrated an independent association between black race and 5-year risk for major adverse cardiac events (hazard ratio: 1.28; 95% confidence interval: 1.05 to 1.57; p = 0.01).In the present large-scale individual patient data pooled analysis, comorbidities were significantly more frequent in minority-group patients than in white patients enrolled in coronary stent randomized controlled trials. After accounting for these differences, black race was an independent predictor of worse outcomes, whereas Hispanic ethnicity and Asian race were not. Further research examining race-based outcomes after percutaneous coronary intervention is warranted to understand these differences.

The aim of this study was to determine 1-year safety and efficacy after treatment with the COMBO and Orsiro stents.The COMBO stainless-steel stent has an anti-CD34For this analysis we included European patients from the COMBO collaboration, a patient-level pooling of 2 prospective all-comers registries of COMBO stent implantation (n = 2,775), and all patients randomized to the Orsiro stent (n = 1,169) from the Dutch BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) randomized trial. The main outcome of interest was 1-year target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization evaluated using propensity score-matched analysis.At baseline, COMBO patients were older and had more insulin-treated diabetes, renal insufficiency, and other comorbidities. However, Orsiro patients included more current smokers and more acute coronary syndrome presentations. Orsiro patients also received longer stents and had more complex target lesions. After propensity score-matched analysis (n = 862/arm), 1-year target lesion failure occurred in 4.1% of COMBO-treated and 2.7% of Orsiro-treated patients (hazard ratio: 1.55; 95% confidence interval: 0.92 to 2.62; p = 0.10). Definite stent thrombosis occurred in 0.5% of COMBO-treated and 0.5% of Orsiro-treated patients (p = 0.99).A propensity score-matched comparison of all comers treated with the COMBO or Orsiro stent showed no statistically significant differences. Stent thrombosis risk was low and similar between the stents. (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population [BIO-RESORT], NCT01674803; MASCOT-Post Marketing Registry [MASCOT], NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE Reg], NCT01874002).

The responsibilities of the interventional cardiologist (IC) have evolved in contemporary practice to include substantial acute care clinical duties outside of the cardiac catheterization laboratory. In particular, the IC has assumed a central role in the global management of myocardial infarction and other acute coronary syndromes in the intensive care unit and beyond. These duties have expanded to include many nonprocedural tasks. The Interventional Section Leadership Council (ISLC) of the American College of Cardiology (ACC) therefore recommends: 1) these implications should be directly considered in the ACC’s future planning and policy statements concerning manpower, competence, education, and reimbursement; 2) the development of an acute care cardiology subspecialty should be undertaken; 3) steps should be taken to adjust the number of ICs primarily on the basis of optimizing procedural volume and quality; and 4) the annual number of coronary interventions performed should not solely define competence in the future, but should include the performance of acute cardiology responsibilities.

The authors sought to determine the factors that influence fellows-in-training (FITs) to pursue a career in interventional cardiology (IC) and how these differ by sex.Despite increases in the proportion of women across numerous medical and surgical specialties over the last decade, IC still ranks at the bottom in terms of representation of women. It is unclear why this maldistribution persists.An online survey of cardiovascular FITs was conducted under the direction of the American College of Cardiology Women in Cardiology Leadership Council to assess FIT perspectives regarding subspecialty choices.Of 574 respondents, 33% anticipated specializing in IC. Men were more likely to choose IC than women (39% men, 17% women, odds ratio: 3.98 [95% confidence interval: 2.38 to 6.68]; p 0.001). Men were more likely to be married (p = 0.005) and have children (p = 0.002). Among married FITs, male IC FITs were more likely to have spouses who do not work (p = 0.003). Although men were more likely to be influenced by positive attributes to pursue IC, women were significantly more likely to be influenced negatively against pursuing the field by attributes including greater interest in another field (p = 0.001), little job flexibility (p = 0.02), physically demanding nature of job (p = 0.004), radiation during childbearing (p 0.001), "old boys' club" culture (p 0.001), lack of female role models (p 0.001), and sex discrimination (p 0.001).Many factors uniquely dissuade women from pursuing IC compared with men, largely related to the culture of IC as a subspecialty. Targeted resolution of these specific factors may provide the most impact in reducing sex imbalances in the field.

Women have historically been underrepresented in clinical trials evaluating cardiovascular devices. Existing initiatives through government agencies have made some progress, but contemporary rates of female clinical trial participation leave much room for improvement. This position paper provides a narrative review and investigates reasons for the underrepresentation of women in cardiovascular trials. The observed differences in safety and/or effectiveness of devices in women warrant a campaign to increase their trial participation with the aim of better understanding and improving outcomes. The authors propose a multifaceted approach to increasing female enrollment through the development of a national public awareness and education campaign aimed to inform women, clinician-providers, and clinical research personnel of these differences. Finally, the authors visit some barriers relevant to women and recommend ways to facilitate their participation in clinical trials through multistakeholder engagement.

The aim of this study was to evaluate 1-year clinical safety and efficacy of the dual-therapy COMBO stent in a large, all-comers patient-level pooled cohort.The COMBO stent (OrbusNeich Medical, Fort Lauderdale, Florida) is a novel stent with abluminal sirolimus elution from a biodegradable polymer and a luminal pro-healing anti-CD34+ antibody layer, which attracts circulating endothelial progenitor cells. These endothelial progenitor cells can quickly mature into normal endothelium, providing rapid endothelialization.The MASCOT (Multinational Abluminal Sirolimus Coated biO-engineered stenT) (N = 2,614, 61 global sites) and REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt Post Market Registry) (N = 1,000, 9 European sites) registries are 2 prospective, multicenter studies evaluating clinical outcomes after attempted COMBO stent placement in all-comer patients undergoing percutaneous coronary intervention. In this patient-level pooled analysis we analyzed 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Furthermore, we determined predictors of 1-year TLF.A total of 3,614 patients (63.5 ± 11.2 years of age; 23.8% women) were included in this analysis. The prevalence of diabetes mellitus was 29.3%, and 54.3% patients presented with acute coronary syndrome. The primary endpoint of 1-year TLF occurred in 140 (3.9%) patients, with incidence of cardiac death in 1.6%, target vessel myocardial infarction in 1.2%, clinically driven target lesion revascularization in 2.2%, and definite stent thrombosis in 0.5% patients. Insulin-treated diabetes mellitus, chronic renal failure, and American College of Cardiology/American Heart Association lesion type B2/C were independent predictors of 1-year TLF.In this large patient-level pooled analysis of patients treated with the dual-therapy COMBO stent excellent results at 1-year were observed. (MASCOT - Post Marketing Registry [MASCOT]; NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the COMBO Stent [REMEDEE Reg]; NCT01874002).

The aim of this study was to compare complete revascularization with a culprit-only strategy in patients presenting with ST-segment elevation myocardial infarction (MI) and multivessel disease by a meta-analysis of randomized trials.Although several trials have compared complete with culprit-only revascularization in ST-segment elevation MI, it remains unclear whether complete revascularization may lead to improvement in hard endpoints (death and MI).Randomized trials comparing complete revascularization with culprit-only revascularization in patients with ST-segment elevation MI without cardiogenic shock were identified by a systematic search of published research. Random-effects meta-analysis was performed, comparing clinical outcomes in the 2 groups.Eleven trials were identified, including a total of 3,561 patients. Compared with a culprit-only strategy, complete revascularization significantly reduced risk for death or MI (relative risk [RR]: 0.76; 95% confidence interval [CI]: 0.58 to 0.99; p = 0.04). Meta-regression showed that performing complete revascularization at the time of primary percutaneous coronary intervention (PCI) was associated with better outcomes (p = 0.016). The 6 trials performing complete revascularization during primary PCI (immediate revascularization) were associated with a significant reduction in risk for both total mortality (RR: 0.62; 95% CI: 0.39 to 0.97; p = 0.03) and MI (RR: 0.40; 95% CI: 0.25 to 0.66; p 0.001), whereas the 5 trials performing only staged revascularization did not show any significant benefit in either total mortality (RR: 1.02; 95% CI: 0.65 to 1.62; p = 0.87) or MI (RR: 1.04; 95% CI: 0.48 to 1.68; p = 0.86).When feasible, complete revascularization with PCI can significantly reduce the combined endpoint of death and MI. Complete revascularization performed during primary PCI was also associated with significant reductions in both total mortality and MI, whereas staged revascularization did not improve these outcomes.

The authors sought to investigate the association between P2YThe association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear.Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation.Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2YHigher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y

This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2YCompared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p0.05 for all subgroups).Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).

The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging.TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease.SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume.Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p 0.001), verbal memory (p 0.001), and visual memory (p 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations.There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

In this analysis of 2-year outcomes in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) study, the authors sought to examine the independent associations between platelet reactivity to both aspirin and clopidogrel and subsequent outcomes.The relationship between platelet reactivity and long-term adverse events following implantation of drug-eluting stents (DES) has been incompletely characterized.The ADAPT-DES study was a multicenter registry of patients undergoing routine platelet function testing following percutaneous coronary intervention with DES. The primary study endpoint was definite or probable stent thrombosis (ST); other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding.A total of 8,582 patients were enrolled between 2008 and 2010; 46.3% of patients were on dual antiplatelet therapy at 2 years without discontinuation. At 2 years, definite or probable ST occurred in 92 patients (1.07%). In patients treated with dual antiplatelet therapy continuously for 2 years, high platelet reactivity on clopidogrel was independently associated with definite or probable ST (adjusted hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.27 to 3.67; p = 0.003), myocardial infarction (adjusted HR: 1.35; 95% CI: 1.05 to 1.74; p = 0.02), freedom from clinically relevant bleeding (adjusted HR: 0.74; 95% CI: 0.62 to 0.90; p = 0.002), and all-cause mortality (adjusted HR: 1.36; 95% CI: 1.01 to 1.85; p = 0.04). Between years 1 and 2, high platelet reactivity was not associated with the very late ST and in patients on aspirin monotherapy, aspirin hyporesponsiveness was not associated with adverse outcomes.The present study confirms the strong relationship of high platelet reactivity on clopidogrel to 2-year ischemic and bleeding outcomes after DES. The majority of stent-related events occurred within the first year.

The aim of this study was to investigate the efficacy and safety of intraprocedural embolic protection (EP) during transcatheter aortic valve replacement (TAVR).Randomized controlled trials (RCTs) investigating the efficacy of EP devices during TAVR were relatively underpowered.A systematic review and study-level meta-analysis was performed of randomized controlled trials that tested the efficacy and safety of EP during TAVR. Trials using any type of EP and TAVR vascular access were included. Primary imaging efficacy endpoints were total lesion volume and number of new ischemic lesions. Primary clinical efficacy endpoints were any deterioration in National Institutes of Health Stroke Scale and Montreal Cognitive Assessment scores at hospital discharge. Primary analyses were performed using the intention-to-treat approach.Four randomized clinical trials (total n = 252) were included. Use of EP was associated with lower total lesion volume (standardized mean difference -0.65; 95% confidence interval [CI]: -1.06 to -0.25; p = 0.002) and smaller number of new ischemic lesions (standardized mean difference -1.27; 95% CI: -2.45 to -0.09; p = 0.03). EP was associated with a trend toward lower risk for deterioration in National Institutes of Health Stroke Scale score at discharge (risk ratio: 0.55; 95% CI: 0.27 to 1.09; p = 0.09) and higher Montreal Cognitive Assessment score (standardized mean difference 0.40; 95% CI: 0.04 to 0.76; p = 0.03). Risk for overt stroke and all-cause mortality were nonsignificantly lower in the EP group.Use of EP seems to be associated with reductions in imaging markers of cerebral infarction and early clinical neurological effectiveness in patients undergoing TAVR.

The aim of this study was to understand the impact of the timing of ischemic and hemorrhagic events after percutaneous coronary intervention (PCI) with drug-eluting stents on subsequent mortality.These events have been strongly associated with subsequent death.In the multicenter, prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents) study, patients at 11 clinical sites with successful PCI with drug-eluting stents underwent assessment of platelet function and were followed for 2 years. Events occurring after PCI-definite or probable stent thrombosis (ST), myocardial infarction (MI) not related to ST, and clinically relevant bleeding (CB)-were classified as early (≤30 days), late (31 to 365 days), or very late (365 days). Mortality within 30 days of each event was estimated by Kaplan-Meier methodology. Cox regression multivariate modeling was used to analyze the relationship between each event (as a time-updated variable) and mortality over the entire study period.Among 8,582 patients, 1,060 (12.4%) had events-691 (8.1%) had CB, 294 (3.4%) had MI, and 75 (0.9%) had ST-and 7,522 (87.6%) had no events. The highest risk was associated with early ST (38.5% mortality at 30 days after the event), whereas very late MI (7.5%) and late CB (7.3%) were less dangerous. By multivariate analysis, each event was independently predictive of death, with hazard ratios of 2.4, 1.8, and 11.4, respectively (p 0.0001).Approximately 1 in 8 patients successfully undergoing PCI with drug-eluting stents had CB, MI, or ST during the ensuing 2 years. These events are associated with an increased hazard of mortality, particularly within the first 30 days following the event, warranting efforts to prevent their occurrence.

The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI).Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI.Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor.In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI).The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized.A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression.Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding.Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy.

This study sought to assess sex differences in chest pain after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES).Sex-based data on chest pain after PCI with DES are scarce.The authors performed a patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials, in which patients were treated with newer generation permanent polymer-coated DES. At 1 and 2 years, clinical follow-up was available in 99.8% and patient-reported chest pain data in 94.1% and 93.6%, respectively.Among all 3,202 patients, the 871 (27.2%) women were older (67.5 ± 10.2 years vs. 62.8 ± 10.6 years; p0.001) and had more cardiovascular risk factors: diabetes (24.2% vs. 17.8%; p0.001), hypertension (63.6% vs. 51.6%; p0.001), and positive family history (54.5% vs. 50.1%; p = 0.03). At 1- and 2-year follow-up, women reported more clinically relevant chest pain (16.3% vs. 10.5%; p0.001, and 17.2% vs. 11.1%; p0.001, respectively). Multivariate analysis demonstrated that female sex independently predicted clinically relevant chest pain at 1- and 2-year follow-up both during daily activities and at minimum physical exertion/at rest (1 year adjusted odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2 to 2.4; p = 0.002; and adjusted OR: 1.8; 95% CI: 1.3 to 2.5; p0.001; 2-year adjusted OR: 1.8; 95% CI: 1.3 to 2.6; p0.001; and adjusted OR: 1.7; 95% CI: 1.3 to 2.3; p = 0.001). Nevertheless, the 2-year rates of death, myocardial infarction, revascularization, stent thrombosis, and various composite clinical endpoints were similar for both sexes.Although the incidence of adverse cardiovascular events was low and similar for both sexes, women showed a statistically significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction.

This study sought to determine the extent to which individual components of intraprocedural thrombotic events (IPTEs) are associated with adverse events.IPTEs occurring during percutaneous coronary intervention (PCI) are associated with adverse in-hospital and late outcomes in patients with acute coronary syndromes.A total of 6,591 patients who underwent PCI for non-ST-segment elevation acute coronary syndromes/ST-segment elevation myocardial infarction in the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) and HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trials underwent detailed frame-by-frame core laboratory angiographic analysis to assess for IPTEs. The associations of IPTE components with death, major bleeding, and major adverse cardiac events at 30 days were assessed using univariable analyses and multivariable models.The overall incidence of IPTEs was 7.7%, with a greater incidence in ST-segment elevation myocardial infarction patients (12.2%) compared with non-ST-segment elevation acute coronary syndromes patients (3.5%). Specific components of IPTEs included no-reflow/slow reflow in 58.0%, new/worsened thrombus in 35.3%, distal embolization in 34.9%, abrupt closure in 19.8%, and intraprocedural stent thrombosis (IPST) in 9.5% of patients. Each IPTE component was independently associated with 30-day death, major bleeding, and MACE in multivariable models, with the strongest association observed for IPST (MACE hazard ratio: 7.51 [95% confidence interval: 4.36 to 12.94]).The occurrence of IPTEs is not infrequent among high-risk acute coronary syndromes patients undergoing PCI, and each IPTE component was associated with subsequent adverse events. Although IPST represented 10% of IPTE events overall, it was the component with the strongest association with adverse events.

The purpose of this study was to evaluate the efficacy and long-term outcomes of a novel polymer/carrier-free drug-coated stent (DCS) in patients with de novo coronary lesions.The BioFreedom (BFD) DCS incorporates a low-profile, stainless-steel platform, with a surface that has been modified to create a selectively microstructured abluminal surface that allows adhesion and further release of Biolimus A9 (Biosensors Europe SA, Morges, Switzerland).A total of 182 patients (183 lesions) were randomized into a 1:1:1 ratio for treatment with BFD "standard dose" (BFD) or BFD "low dose" (BFD-LD) versus first-generation paclitaxel-eluting stents (PES) at 4 sites in Germany.Baseline and procedural characteristics were well matched. At 4-month angiographic follow-up (Cohort 1, n = 75), in-stent late lumen loss (LLL) was significantly lower with BFD and BFD-LD versus PES (0.08 and 0.12 mm vs. 0.37 mm, respectively; p0.0001 for BFD vs. PES, and p = 0.002 for BFD-LD vs. PES). At 12 months (Cohort 2, n = 107), in-stent LLL (primary endpoint) was 0.17 mm in BFD versus 0.35 mm in PES (p = 0.001 for noninferiority; p = 0.11 for superiority); however, the BFD-LD (0.22 mm) did not reach noninferiority (p = 0.21). At 5 years (175 of 182), there were no significant differences in major adverse cardiac events (23.8%, 26.4%, and 20.3%) and clinically indicated target lesion revascularization (10.8%, 13.4%, and 10.2%) for BFD, BFD-LD, and PES, respectively; also, there was no definite/probable stent thrombosis reported.The BFD, but not the BFD-LD, demonstrated noninferiority versus PES in terms of in-stent LLL, a surrogate of neointimal hyperplasia, at 12-month follow-up. At 5 years, clinical event rates were similar, without occurrence of stent thrombosis in all groups. (BioFreedom FIM Clinical Trial; NCT01172119).

This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation.Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes.In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU).The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p0.001). However, there were no significant independent associations between the level of PRU and mortality.In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).

The invention of intracoronary stents greatly increased the safety and applicability of percutaneous coronary interventions. At this time,1 million coronary stent implantations are performed each year in the United States. But together with the growing use of stents, stent thrombosis, the most feared complication after stent implantation, has emerged as an important entity to understand and prevent. Adjunct pharmacological therapy, stent design, and deployment technique have been adjusted ever since to reduce its occurrence. The current clinical overview of stent thrombosis ranges from its pathophysiology to current state-of-the-art technical and pharmacological recommendations to avoid this complication.

Our aim was to study the impact of delay from symptom onset to first coronary device on infarct size and clinical outcomes at 30 days and 1 year in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention.Longer delay from symptom onset to reperfusion has been linked to increased mortality and worse clinical outcome. The mechanisms underpinning this association are not entirely clear.The INFUSE-AMI trial (INFUSE-Anterior Myocardial Infarction) randomized patients with anterior STEMI undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation within 5 h of symptom onset to intralesion (IL) bolus abciximab versus no abciximab and to thrombus aspiration versus no aspiration. The primary endpoint was contrast magnetic resonance infarct size (IS) (percentage of left ventricular mass) at 30 days. Time to reperfusion was classified as3 versus ≥3 h.There were 280 patients (62%) with3-h delay and 170 patients (38%) with ≥3-h delay. Patients with longer delay were significantly older, more often women, and diabetic. Earlier reperfusion was not associated with higher rates of final Thrombolysis In Myocardial Infarction flow grade 3 or myocardial blush grade 2/3, but was an independent predictor of smaller IS (p = 0.02 by multivariable linear regression). Mortality at 1 year was reduced in patients with shorter delay to reperfusion (4.0% vs. 9.2%, p = 0.02).In patients with large anterior myocardial infarction undergoing relatively early reperfusion, longer delays to reperfusion were associated with larger IS and 1-year mortality, but not with reduced reperfusion success. (The INFUSE - Anterior Myocardial Infarction [AMI] Study; NCT00976521).

This study sought to investigate the prognostic value of access site bleeding (ASB) and non-ASB for recurrent ischemic outcomes and mortality in patients with ST-segment elevation myocardial infarction (STEMI).The prognostic value of ASB-related complications after STEMI is subject to debate.The prognostic value of ASB and non-ASB for 1-year mortality, recurrent myocardial infarction (MI), stent thrombosis, and stroke was investigated in 2,002 STEMI patients undergoing primary percutaneous coronary intervention. In addition, we performed a meta-analysis of studies investigating the prognostic value of ASB and non-ASB in patients undergoing percutaneous coronary intervention.Seventy-four patients (3.7%) were treated by radial access. ASB developed in 124 patients (6.3%) and non-ASB developed in 102 (5.2%). By multivariable analysis, ASB was not associated with a higher risk of 1-year mortality (hazard ratio [HR]: 1.03; p = 0.89), recurrent MI (HR: 1.16; p = 0.64), stent thrombosis (HR: 0.55; p = 0.42), or stroke (HR: 0.47; p = 0.31). Non-ASB was independently associated with 1-year mortality (HR: 2.77; p0.001) and stent thrombosis (HR: 3.10; p = 0.021), but not with recurrent MI and stroke. In a meta-analysis including 495,630 patients, non-ASB was associated with a greater adjusted risk of subsequent 1-year mortality than ASB (HR: 1.66; 95% CI: 1.56 to 1.76 and HR: 1.21; 95% CI: 1.11 to 1.31).In STEMI, ASB was not significantly associated with 1-year clinical outcomes, whereas non-ASB was significantly associated with 1-year mortality and stent thrombosis. These results taken together with those of previous studies indicate a greater risk of subsequent mortality in patients with non-ASB.

This study sought to evaluate the short- and long-term outcomes for smokers with non-ST-segment elevation acute coronary syndromes (NSTE-ACS).Smoking has been associated with the "paradox" of reduced mortality after acute myocardial infarction (MI). This is thought to be due to favorable baseline characteristics and less diffuse coronary artery disease (CAD) among smokers.In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients (29.1% smokers) with moderate- to high-risk NSTE-ACS underwent angiography and, if indicated, revascularization.Smokers were significantly younger and had fewer comorbidities than nonsmokers. Incidence of death and MI were comparable at 30 days, although smokers had significantly reduced risks of 30-day major bleeding (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.67 to 0.96; p = 0.016) and 1-year mortality (HR: 0.797, 95% CI: 0.65 to 0.97; p = 0.027). After correction for baseline and clinical differences, smoking was no longer predictive of major bleeding (odds ratio: 1.06, 95% CI: 0.86 to 1.32; p = 0.56) and was associated with higher 1-year mortality (HR: 1.37, 95% CI: 1.07 to 1.7; p = 0.013). This pattern of reversed risk after multivariable correction held true for those smokers requiring percutaneous coronary intervention. Core laboratory angiographic analysis showed that smokers and nonsmokers were comparable in terms of the extent of CAD, Thrombolysis In Myocardial Infarction flow, myocardial blush, and the presence of thrombi.In contrast to the paradox previously described in ST-segment elevation MI, our analysis finds smoking to be an independent predictor of higher 1-year mortality in patients presenting with NSTE-ACS, and our angiographic study demonstrates CAD in smokers that is comparable to that in nonsmokers but evident ∼1 decade earlier. (Acute Catheterization and Urgent Intervention Triage Strategy [ACUITY]; NCT00093158).

This study evaluated the impact of nonculprit vessel myocardial perfusion on outcomes of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) patients.ST-segment elevation myocardial infarction patients have decreased perfusion in areas remote from the infarct-related vessel. The impact of myocardial hypoperfusion of regions supplied by nonculprit vessels in NSTE-ACS patients treated with percutaneous coronary intervention (PCI) is unknown.The angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial included 6,921 NSTE-ACS patients. Complete 3-vessel assessments of baseline coronary TIMI (Thrombolysis In Myocardial Infarction) flow grade and myocardial blush grade (MBG) were performed. We examined the outcomes of PCI-treated patients according to the worst nonculprit vessel MBG identified per patient.Among the 3,826 patients treated with PCI, the worst nonculprit MBG was determined in 3,426 (89.5%) patients, including 375 (10.9%) MBG 0/1 patients, 475 (13.9%) MBG 2 patients, and 2,576 (75.2%) MBG 3 patients. Nonculprit MBG 0/1 was associated with worse baseline clinical characteristics. Patients with nonculprit MBG 0/1 versus MBG 3 had increased rates of 30-day (3.0% vs. 0.7%, p0.0001) and 1-year (4.4% vs. 1.0%, p0.0001) death. Similar results were found among patients with pre-procedural TIMI flow grade 3 in the culprit vessel, where nonculprit vessel MBG 0/1 (hazard ratio: 2.81 [95% confidence interval: 1.63 to 4.84], p = 0.0002) was the strongest predictor of 1-year mortality.Reduced myocardial perfusion in an area supplied by a nonculprit vessel is associated with increased short- and long-term mortality rates in NSTE-ACS patients undergoing PCI. Furthermore, worst nonculprit MBG is able to risk-stratify patients with normal baseline flow of the culprit vessel.

This study sought to assess the contemporary outcomes of patients with prior coronary artery bypass graft (CABG) who present with moderate and high-risk acute coronary syndromes (ACS) and are treated with an early invasive strategy and contemporary antithrombin regimens.The prognosis of patients with ACS and prior CABG in relation to triage strategy and contemporary antithrombotic regimens is unknown.In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%) with ACS managed with an early invasive strategy had previously undergone CABG. Their outcomes were examined according to treatment and randomized antithrombin regimen.Prior CABG was associated with older age, more frequent comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower left ventricular ejection fraction. Patients with versus without prior CABG were less likely to undergo (repeat) CABG and were more likely to be managed medically. At 1 year, patients with versus without prior CABG had higher rates of major adverse cardiac events (MACE) (22.5% vs. 15.2%, p0.0001) due to greater mortality (5.4% vs. 3.9%, p0.0001), myocardial infarction (10.0% vs. 6.8%, p0.0001), and unplanned revascularization (13.1% vs. 8.2%, p0.0001). History of CABG was an independent predictor of MACE. The 1-year MACE rates were not significantly different after randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90 to 1.70).Despite the progress in the treatment of coronary artery disease, patients with prior CABG and ACS have a poor prognosis, substantially worse than for those without prior CABG. Whereas bivalirudin monotherapy was an acceptable treatment for these patients, it did not improve their prognoses.

This study sought to examine the relationship between the aspirin dose prescribed at hospital discharge and long-term outcomes after ST-segment elevation myocardial infarction in patients treated with primary percutaneous coronary intervention (PCI).Patients with ST-segment elevation myocardial infarction who undergo primary PCI are prescribed maintenance aspirin doses that vary between 75 and 325 mg daily. Whether the dose of aspirin affects long-term patient outcomes is unknown.We compared 3-year outcomes in patients who were prescribed high-dose (200 mg daily) versus low-dose (≤200 mg daily) aspirin from the large-scale HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial.Among 2,851 patients, 2,289 patients (80.3%) were discharged on low-dose aspirin and 562 patients (19.7%) were discharged on high-dose aspirin. Patients discharged on high-dose rather than low-dose aspirin were more likely to have a history of hypertension, hyperlipidemia, family history of premature coronary disease, prior treatment with PCI or coronary artery bypass surgery, and to be enrolled in the United States. Patients discharged on high-dose aspirin had higher 3-year rates of major adverse cardiovascular events, reinfarction, ischemic target vessel revascularization, major bleeding, and stent thrombosis. After multivariable analysis, discharge on high-dose aspirin was an independent predictor of major bleeding (hazard ratio: 2.80; 95% confidence interval: 1.31 to 5.99; p = 0.008), but not of adverse ischemic events.In patients with ST-segment elevation myocardial infarction undergoing primary PCI, discharge on high-dose rather than low-dose aspirin may increase the rate of major bleeding without providing additional ischemic benefit.

The aim of this study was to examine the incidence, correlates, and consequences of intra-procedural stent thrombosis (IPST) in patients with acute coronary syndromes (ACS).Stent thrombosis (ST) is a rare but serious complication of percutaneous coronary intervention (PCI). The Academic Research Consortium definition of ST excludes events occurring during PCI.Angiograms from the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) and HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trials were reviewed frame-by-frame at an independent core laboratory for the occurrence of IPST. Patients with versus without IPST were compared to identify baseline characteristics associated with IPST and demonstrate the independent association between IPST and adjudicated events at 30 days and 1 year.Intra-procedural ST occurred in 47 (0.7%) of 6,591 patients. The occurrence of IPST was associated with ST-segment elevation myocardial infarction presentation, high white blood cell count, treatment of thrombotic and bifurcation lesions, bivalirudin monotherapy, bail-out IIb/IIIa inhibitor use, and implantation of bare-metal (rather than drug-eluting) stents. Major adverse ischemic events were markedly higher in patients with versus without IPST, including mortality at 30 days (12.9% vs. 1.4%, p0.0001) and 1 year (12.9% vs. 3.1%, p0.0001). Out-of-lab Academic Research Consortium definite or probable ST also occurred significantly more often among IPST patients at 30 days (17.4% vs. 1.8%, p0.0001) and 1 year (19.9% vs. 2.7%, p0.0001). Intra-procedural ST was a significant independent predictor of 1-year mortality (hazard ratio: 3.86, 95% confidence interval: 1.66 to 9.00, p = 0.002).Intra-procedural ST is a relatively rare complication of PCI in ACS but is strongly associated with subsequent out-of-lab ST and mortality. Intra-procedural ST should be considered as a distinct category of ST and routinely reported, particularly for ACS patients.

This study sought to investigate the impact of chronic kidney disease (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) with different antithrombotic strategies.CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI.HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial was a multicenter, international, randomized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) during primary PCI in STEMI. CKD, defined as creatinine clearance60 ml/min, was present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for 3 years. Net adverse cardiac event (NACE) was defined as the composite of death, reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or non-coronary artery bypass grafting (CABG)-related major bleeding.Patients with CKD compared with patients without had higher rates of NACE (41.4% vs. 23.8%, p0.0001), death (18.7% vs. 4.4%, p0.0001), and major bleeding (19.3% vs. 6.7%, p0.0001). Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51, 95% confidence interval: 1.21 to 1.87, p0.001). Patients with CKD randomized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p = 0.88) at 3 years. In patients with CKD, there was no difference in the rates of TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1% vs. 15.1%, p = 0.8).STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD. In patients with CKD, there appears to be no benefit of bivalirudin compared with heparin + GPI, or DES versus BMS during primary PCI in improving clinical outcomes.

We sought to evaluate the safety and efficacy of bivalirudin compared with glycoprotein IIb/IIIa inhibitors (GPI) in diabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Prior studies have demonstrated that GPI are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI.In the multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI were randomized to bivalirudin or unfractionated heparin plus a GPI. Clinical outcomes were analyzed at 30 days and 1 year in patients with diabetes.Diabetes mellitus was present in 593 patients (16.5%). The rates of cardiac death were significantly lower in diabetic patients treated with bivalirudin compared with heparin plus GPI (30 days: 2.1% vs. 5.5%, p = 0.04; 1 year: 2.5% vs. 7.1%, p = 0.01), and bivalirudin resulted in lower 30-day rates of stroke (0% vs. 2%, p = 0.02). There were no significant differences among diabetic patients randomized to bivalirudin versus heparin plus GPI in the 1-year rates of major adverse cardiac events (14.2% vs. 16.2%, p = 0.44), major bleeding (8.7% vs. 10.7%, p = 0.42), or stent thrombosis (4.2% vs. 3.8%, p = 0.85). By interaction testing, the relative effects of bivalirudin compared with heparin plus GPI were not significantly different in patients with and without diabetes.In patients with diabetes mellitus presenting with STEMI undergoing primary PCI, anticoagulant therapy with bivalirudin compared with heparin plus GPI is safe and effective and might reduce cardiac mortality at 30 days and 1 year. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality.Bleeding complications after PCI have been independently associated with early and late mortality.This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)-related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality.A non-CABG-related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG-related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality.Non-CABG-related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

The aim of this study was to understand the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infarction (AMI).Attenuated plaques identified by grayscale intravascular ultrasound (IVUS) might predict transient deterioration in coronary flow and/or no-reflow during percutaneous coronary intervention (PCI).We analyzed clinical, angiographic, and IVUS data from 364 patients (n = 364 infarct-related arteries) enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. No-reflow was final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 in the absence of mechanical obstruction. Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1 mm, scoring the angle as 1 to 4 (corresponding to90°, 90° to 180°, 180° to 270°, or 270° to 360°, respectively), summing the scores, and normalizing for analysis length.Overall, 284 (78.0%) patients had attenuated plaques; no-reflow occurred in 37 (10.2%). Patients with no-reflow had a higher mean attenuation score (median [interquartile range] 2.2 [0.0 to 2.8] vs. 1.3 [0.7 to 1.8], p0.001), lower baseline left ventricular ejection fraction (52.8% [43.2% to 61.5%] vs. 61.4% [52.2% to 68.1%], p = 0.002), and more baseline angiographic thrombus (89.2% vs. 74.1%, p = 0.043) with no differences in post-PCI stent expansion versus patients without no-reflow. Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 points (90° to 180°, sensitivity of 81.5%, and specificity of 80.5%).Attenuated plaque was present in three-quarters of patients with AMI. The amount of attenuated plaque strongly correlated with no-reflow; the larger the attenuated plaque, the greater the likelihood of no-reflow. (Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [TAXUS™] or Uncoated Bare Metal Stent [EXPRESS2™]; NCT00433966).

The objective of this study is to investigate the incidence and clinical implications of thrombus on baseline angiography among patients presenting with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).Given current advances in the pharmacological and mechanical treatment of ACS patients managed with an early invasive strategy, the incidence and prognostic importance of pre-procedural lesion thrombus is warranted.In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, a total of 3,627 patients with moderate- and high-risk ACS undergoing PCI had their baseline and final post-PCI angiograms analyzed by an independent angiographic core laboratory.Patients with thrombus (n = 530 [15%]) compared with those without thrombus had higher rates of impaired final epicardial coronary flow (final Thrombolysis In Myocardial Infarction [TIMI] flow grade 3: 89.6% vs. 97.1%, p0.0001). Thrombus was an independent predictor of 30 day death (odds ratio [OR]: 3.16 [95% confidence interval (CI): 1.20 to 8.37], p = 0.02), and myocardial infarction (MI) at 30 days (OR: 1.62 [95% CI: 1.17 to 2.24], p = 0.003) and at 1 year (OR: 1.56 [95% CI: 1.16 to 2.08], p = 0.003). Patients with thrombus had significantly higher rates of stent thrombosis (ST) compared with patients without thrombus at 30 days (2.8% vs. 1.1%, p = 0.002) and at 1 year (3.7% vs. 1.8%, p = 0.003), and thrombus was an independent predictor of ST at both 30 days (OR: 2.61 [95% CI: 1.38 to 4.91]) and 1 year (OR: 2.98 [95% CI: 1.64 to 5.42]).Pre-procedural thrombus was present in 15% of moderate- and high-risk ACS patients undergoing PCI in the ACUITY trial. Baseline thrombus predicts increased ischemic complications at 30 days including a 3-fold increased risk of death as well as MI up to 1 year. Further evaluation of adjunctive pharmacotherapy is needed in this high-risk population.