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Immunophenotyping has been the primary assay for characterization of immune cells from patients undergoing therapeutic treatments in clinical research, which is critical for understanding disease progression and treatment efficacy. Currently, flow cytometry has been the dominant methodology for characterizing surface marker expression for immunological research. Flow cytometry has been proven to be an effective and efficient method for immunophenotyping, however, it requires highly trained users and a large time commitment. Recently, a novel image cytometry system (Cellaca® PLX Image Cytometer, Revvity Health Sciences, Inc., Lawrence, MA) has been developed as a complementary method to flow cytometry for performing rapid and high-throughput immunophenotyping. In this work, we demonstrated an image cytometric screening method to characterize immune cell populations, streamlining the analysis of routine surface marker panels. The T cell, B cell, NK cell, and monocyte populations of 46 primary PBMC samples from subjects enrolled in autoimmune and oncological disease study cohorts were analyzed with two optimized immunophenotyping staining kits: Panel 1 (CD3, CD56, CD14) and Panel 2 (CD3, CD56, CD19). We validated the proposed image cytometry method by comparing the Cellaca® PLX and the Aurora TM flow cytometer (Cytek Biosciences, Fremont, CA). The image cytometry system was employed to generate bright field and fluorescent images, as well as scatter plots for multiple patient PBMC samples. In addition, the image cytometry method can directly determine cell concentrations for downstream assays. The results demonstrated comparable CD3, CD14, CD19, and CD56 cell populations from the primary PBMC samples, which showed an average of 5% differences between flow and image cytometry. The proposed image cytometry method provides a novel research tool to potentially streamline immunophenotyping workflow for characterizing patient samples in clinical studies., Competing Interests: Declaration of Competing Interest The authors SP, JIM, HM, AHL, SKG, BL, and LLC declare competing financial interests. The Cellaca® PLX Image Cytometer used to demonstrate high-throughput immunophenotypic screening method was from Revvity Health Sciences, Inc., an indirect parent company of Nexcelom Biosciences, LLC. All trademarks, service marks, trade names, and brand names are the property of their respective owners., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Managing percutaneous coronary intervention (PCI) patients with atrial fibrillation (AF) presents challenges given that there are several potential antithrombotic therapy (ATT) strategies., Aims: We examined ATT patterns, agreement between subjective physician ratings and validated risk scores, physician-patient perceptions influencing ATT and 1-year outcomes., Methods: The AVIATOR 2 prospective registry enrolled 514 non-valvular AF-PCI patients from 11 sites. Treating physicians selected ATT and completed smartphone surveys rating stroke and bleeding risks, compared against CHA 2 DS 2 -VASc and HAS-BLED scores. Patients completed surveys regarding treatment understanding. Primary outcomes were 1-year major adverse cardiac or cerebrovascular events (MACCE: composite of death, myocardial infarction, definite/probable stent thrombosis, stroke, target lesion revascularisation) and actionable bleeding (Bleeding Academic Research Consortium 2, 3 or 5)., Results: The mean patient age was 73.2±9.0 years, including 25.8% females. Triple therapy (TT: 1 anticoagulant and 2 antiplatelet agents) was prescribed in 66.5%, dual antiplatelet therapy (DAPT) in 20.7% and dual therapy (1 anticoagulant+1 antiplatelet agent) in 12.8% of patients. Physician ratings and validated risk scores showed poor agreement (stroke: kappa=0.03; bleeding: kappa=0.07). Physicians rated bleeding-related safety (93.8%) as the main factor affecting ATT choice. Patients worried about stroke over bleeding (50.6% vs 14.8%). No group differences by ATT strategy were observed in 1-year MACCE (TT 14.1% vs dual therapy 12.7% vs DAPT 18.5%; p=0.25), or actionable bleeding (14.7% vs 7.9% vs 15.1%, respectively; p=0.89)., Conclusions: The AVIATOR 2 study is the first digital health study examining physician-patient perspectives on ATT choices after AF-PCI. TT was the most common strategy without differences in 1-year outcomes in ATT strategy. Physicians rated safety first when prescribing ATT; patients feared stroke over bleeding., Clinicaltrials: gov: NCT02362659.

Introduction: Multiple trials have demonstrated broad performance ranges for tests attempting to detect coronary artery disease. The most common test, SPECT, requires capital-intensive equipment, the use of radionuclides, induction of stress, and time off work and/or travel. Presented here are the development and clinical validation of an office-based machine learned algorithm to identify functionally significant coronary artery disease without radiation, expensive equipment or induced patient stress., Materials and Methods: The IDENTIFY trial (NCT03864081) is a prospective, multicenter, non-randomized, selectively blinded, repository study to collect acquired signals paired with subject meta-data, including outcomes, from subjects with symptoms of coronary artery disease. Time synchronized orthogonal voltage gradient and photoplethysmographic signals were collected for 230 seconds from recumbent subjects at rest within seven days of either left heart catheterization or coronary computed tomography angiography. Following machine learning on a proportion of these data ( N = 2,522), a final algorithm was selected, along with a pre-specified cut point on the receiver operating characteristic curve for clinical validation. An unseen set of subject signals ( N = 965) was used to validate the algorithm., Results: At the pre-specified cut point, the sensitivity for detecting functionally significant coronary artery disease was 0.73 (95% CI: 0.68-0.78), and the specificity was 0.68 (0.62-0.74). There exists a point on the receiver operating characteristic curve at which the negative predictive value is the same as coronary computed tomographic angiography, 0.99, assuming a disease incidence of 0.04, yielding sensitivity of 0.89 and specificity of 0.42. Selecting a point at which the positive predictive value is maximized, 0.12, yields sensitivity of 0.39 and specificity of 0.88., Conclusion: The performance of the machine learned algorithm presented here is comparable to common tertiary center testing for coronary artery disease. Employing multiple cut points on the receiver operating characteristic curve can yield the negative predictive value of coronary computed tomographic angiography and a positive predictive value approaching that of myocardial perfusion imaging. As such, a system employing this algorithm may address the need for a non-invasive, no radiation, no stress, front line test, and hence offer significant advantages to the patient, their physician, and healthcare system., Competing Interests: This study was supported by CorVista Health. The funder had the following involvement in the study: the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication. HG, IS, WS, TB, FF, AK, and EL were employees of CorVista Health. MGR was a member of the Medical Advisory Board for CorVista Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stuckey, Meine, McMinn, Depta, Bennett, McGarry, Carroll, Suh, Steuter, Roberts, Gillins, Lange, Fathieh, Burton, Khosousi, Shadforth, Sanders and Rabbat.)

Background: Data on geographical variations in dual antiplatelet therapy (DAPT) cessation and the impact on outcomes after percutaneous coronary intervention (PCI) are limited. We sought to evaluate geographical patterns of DAPT cessation and associated outcomes in patients undergoing PCI in the United States versus Europe., Methods: Analyzing data from the PARIS registry, we studied 3,660 U.S. patients (72.9%) and 1,358 European patients (27.1%) that underwent PCI with stent implantation. DAPT cessation was classified as physician-recommended discontinuation, interruption (< 14 days), or disruption due to bleeding or noncompliance. The primary endpoint was 2-year major adverse cardiovascular events (MACE) defined as a composite of cardiac death, stent thrombosis, myocardial infarction, or target lesion revascularization., Results: Cardiovascular risk factors were more common in the United States, whereas procedural complexity was greater in Europe. The incidence of 2-year DAPT discontinuation was significantly lower in U.S. versus European patients (30.7% vs. 65.6%; p  < 0.001); however, rates of interruption (13.7% vs. 1.5%, p  < 0.001) and disruption (17.7% vs. 5.1%, p  < 0.001) were higher. DAPT discontinuation was associated with lower adjusted risk, whereas DAPT disruption was associated with greater risk for 2-year MACE, without interaction by region. After adjustment for baseline characteristics and DAPT cessation, 2-year MACE risk was not statistically different between regions (10.3% for Europe vs. 11.9% for U.S., adjusted hazard ratio 0.81, 95% confidence interval 0.65-1.01, p  = 0.065)., Conclusion: DAPT cessation patterns, along with clinical and angiographic risk, vary substantially between PCI patients in the U.S. versus Europe. Despite such differences, cardiovascular risk associated with DAPT cessation remains uniform., Competing Interests: D.C. has received research grant support from Eli Lilly and Astra Zeneca, consulting fees from Eli Lilly, Astra Zeneca, and speaking honoraria from Astra Zeneca. T.H. has received research grant support from Eli Lilly & Company and Daiichi-Sankyo. G.D. has received consulting fees and honoraria from Johnson & Johnson, Sanofi, Covidien, The Medicines Company, Merck, CSL Behring, AstraZeneca, Medtronic, Abbott, Bayer, Boston Scientific, Osprey Medical, and GE Healthcare; and research grant support from Sanofi, Bristol-Myers Squibb, and Eli Lilly & Company/Daiichi-Sankyo. M.G. has received research grant support from Angel Medical Corporation, Atrium Medical Systems, Bayer Corporation, Ikaria, Janssen/Johnson & Johnson Corporation, Lantheus Medical Imaging, Merck & Company, Portola Pharmaceuticals, Roche Diagnostics, Sanofi, Stealth Peptides, St. Jude Medical, Volcano Corporation, and Walk Vascular; consulting fees from AstraZeneca, Baxter Healthcare, Bayer Corporation, CRF, Consensus Medical Communications, CSL Behring, Cytori Therapeutics, Eli Lilly & Company/Daiichi Sankyo, Exeter Group, Genentech, GlaxoSmithKline, Janssen/Johnson & Johnson Corporation, Ortho McNeil, St. Jude Medical, and The Medicines Company; and royalty fees from UpToDate in Cardiovascular Medicine. D.M. has received institutional research grant support from AstraZeneca. M.K. has received consulting fees from Abbott Vascular, Abbott Laboratories, OrbusNeich, Angelmed, Volcano, Biosensors, Svelte, OrbusNeich, Medtronic, and Terumo; and research grant support from Abbott, Terumo, Angelmed, Ikaria, OrbusNeich, Cardiovascular Systems, Inc. (CSI), Eli Lilly & Company, and Medtronic. A.C. has received consulting fees and honoraria from Carbostent and Implantable Devices (CID); and other fees from Direct Flow Medical. A.K. serves on the speaker's bureau of the American College of Cardiology; and has received consulting fees from WebMD. P.G.S. discloses the following relationship: research grant from Bayer, Merck, Sanofi, and Servier, speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer-Ingelheim, Bristol-Myers-Squibb, Lilly, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron, Sanofi, and Servier, received personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Medtronic, Servier, Janssen, CSL Behring, and Regeneron; grants and personal fees from Sanofi; and personal fees and nonfinancial support from The Medicines Company, outside the submitted work. R.M. has received institutional research grant support from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers-Squibb, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has served as a consultant for Abbott Vascular, American College of Cardiology, AstraZeneca, Boston Scientific, CardioKinetix, CSL Behring, Medscape, Shanghai Bracco Sine Pharmaceutical, and Spectranetics; has served on the advisory board for Bristol Myers-Squibb; has received institutional advisory board funding from Bristol-Myers Squibb; has received institutional funding from Claret Medical; owns equity in Claret Medical and Elixir Medical; has served on the executive committee for Janssen Pharmaceuticals and Osprey Medical; has served on the data safety monitoring board for Watermark Research Partners; and has a spouse who has served as a consultant for Abiomed and The Medicines Company., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Patients with chronic kidney disease (CKD) experience high rates of ischemic and bleeding events after percutaneous coronary intervention (PCI), complicating decisions surrounding dual antiplatelet therapy (DAPT). This study aims to determine the pattern and impact of various modes of DAPT cessation for patients with CKD undergoing PCI., Methods and Results: Patients from the PARIS registry (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) were grouped based on the presence of CKD defined as creatinine clearance <60 mL/min. After index PCI, time and mode of DAPT cessation (discontinuation, interruption, and disruption) and clinical outcomes (major adverse cardiac events, stent thrombosis, myocardial infarction, and major bleeding [Bleeding Academic Research Consortium type 3 or 5]) were reported. Over 2 years, patients with CKD (n=839) had higher adjusted risks for death (hazard ratio, 3.16; 95% confidence interval, 2.26-4.41), myocardial infarction (hazard ratio, 2.43; 95% confidence interval, 1.65-3.57), and major bleeding (hazard ratio, 2.21; 95% confidence interval, 1.53-3.19) compared with patients without CKD (n=3745). Rates of DAPT discontinuation within the first year after PCI and disruption were significantly higher for patients with CKD. However, DAPT interruption occurred with equal frequency. Associations between DAPT cessation mode and subsequent risk were not modified by CKD status. Findings were unchanged after propensity matching., Conclusions: Patients with CKD display high and comparable risks for both ischemic and bleeding events after PCI. Physicians are more likely to discontinue DAPT within the first year after PCI among patients with CKD, likely reflecting clinical preferences to avoid bleeding. Risks after DAPT cessation, irrespective of underlying mode, are not modified by the presence or absence of CKD., (© 2018 American Heart Association, Inc.)

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for <14 days. Of the study cohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Percutaneous coronary intervention (PCI) of the left main (LM) or proximal left anterior descending artery (pLAD) is considered high-risk as these segments subtend substantial left ventricular myocardial area. We assessed the patterns and associations between dual antiplatelet therapy (DAPT) cessation and 2-year outcomes in LM/pLAD vs. other PCI from the all-comer PARIS registry., Methods: Two-year major adverse cardiovascular events (MACE) were a composite of cardiac death, myocardial infarction, definite/probable stent thrombosis or target lesion revascularization. DAPT cessation was predefined as physician-guided permanent discontinuation, temporary interruption, or non-recommended disruption due to non-compliance or bleeding., Results: Of the study population (n=5018), 25.0% (n=1252) underwent LM/pLAD PCI and 75.0% (n=3766) PCI to other segments. Compared to others, LM/pLAD patients presented with fewer comorbidities, less frequent acute coronary syndromes but more multivessel and bifurcation disease treated with greater stent lengths. Two-year adjusted risk of MACE (11.4% vs. 11.6%; HR 1.10, 95% CI 0.90-1.34, p=0.36) was similar between LM/pLAD vs. other patients. DAPT discontinuation was significantly higher (43.3% vs. 39.4%, p=0.01) in LM/pLAD patients with borderline significance for lower disruption (10.0% vs. 14.7%, p=0.059) compared to other patients. DAPT discontinuation was not associated with higher risk of MACE in LM/pLAD (HR 0.65, 95% CI 0.34-1.25) or other PCI groups (HR 0.67, 95% CI 0.47-0.95)., Conclusions: LM/pLAD PCI was not an independent predictor of 2-year MACE. Compared to other PCI, patients undergoing LM/pLAD PCI had higher rates of physician recommended DAPT discontinuation, however, discontinuation did not result in greater adverse events., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Elevated white blood cell (WBC) count is associated with increased major adverse cardiovascular events (MACE) in the setting of acute coronary syndrome. The aim of this study was to evaluate whether similar associations persist in an all-comers population of patients undergoing percutaneous coronary intervention in the contemporary era., Methods and Results: In the multicenter, prospective, observational PARIS study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry), 4222 patients who underwent percutaneous coronary intervention in the United States and Europe between July 1, 2009, and December 2, 2010, were evaluated. The associations between baseline WBC and MACE (composite of cardiac death, stent thrombosis, spontaneous myocardial infarction, or target lesion revascularization) at 24-month follow-up were analyzed using multivariable Cox regression. Patients with higher WBC were more often younger, smokers, and with less comorbid risk factors compared with those with lower WBC. After adjustment for baseline and procedural characteristics, WBC remained independently associated with MACE (hazard ratio [HR] per 10 3 cells/μL increase, 1.05 [95% confidence intervals (CI), 1.02-1.09]; P =0.001), cardiac death (HR, 1.10 [95% CI, 1.05-1.17]; P <0.001), and clinically indicated target revascularization (HR, 1.04 [95% CI, 1.00-1.09]; P =0.03) but not stent thrombosis (HR, 1.07 [95% CI, 0.99-1.16]; P =0.10) or spontaneous myocardial infarction (HR, 1.03 [95% CI, 0.97-1.09]; P =0.29). The association between WBC and MACE was consistent in acute coronary syndrome and non-acute coronary syndrome presentations (interaction P =0.15)., Conclusions: Increased WBC is an independent predictor of MACE after percutaneous coronary intervention in a contemporary all-comers cohort. Further studies to delineate the underlying pathophysiologic role of elevated WBC across a spectrum of coronary artery disease presentations are warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00998127., (© 2017 American Heart Association, Inc.)

Background: Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events., Methods: We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation., Results: The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51)., Conclusions: In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI., Methods: The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127., Findings: We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation., Interpretation: In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type., Funding: Bristol-Myers Squibb and Sanofi-Aventis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To compare outcomes between US and non-US (OUS) sites in patients with non ST-elevation acute coronary syndromes (NSTEACS) and to evaluate potential reasons for differences in outcomes., Background: There are little data comparing outcomes at US versus OUS sites in patients with NSTEACS managed with an invasive strategy., Methods: The ACUITY trial randomized 13,819 patients with NSTEACS in 17 countries to an invasive approach with one of three strategies: (1) heparin plus glycoprotein platelet inhibitors (GPI), (2) bivalirudin plus GPI, or (3) bivalirudin alone., Results: US patients were more often female, were younger, heavier, and had more diabetes, prior myocardial infarction (MI), and prior bypass surgery. US patients were less often treated with percutaneous coronary intervention but had more frequent drug-eluting stent use. US patients had lower mortality and higher MI rates at 30 days and 1 year and higher composite ischemic outcome at 30 days. After adjusting for differences in baseline variables, US patients had higher rates of MI and composite ischemic outcome at 30 days and higher rates of MI at 1 year {HR [95% confidence interval (CI)] = 1.36 [1.18-1.56], P < 0.0001} with no differences in mortality. There were no differences in treatment effects comparing bivalirudin with the other strategies between US and OUS sites., Conclusions: US versus OUS patients with NSTEACS had higher adjusted rates of MI and ischemia. The reasons for these differences are not clear but may be due to unmeasured confounders, different thresholds for event reporting, or valid differences in systems of care which may impact outcomes., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: To examine outcomes in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) at US sites versus sites outside the US (OUS)., Methods and Results: In the HORIZONS-AMI trial 3,602 STEMI patients in 11 countries were randomised to primary PCI with bivalirudin versus heparin + glycoprotein IIb/IIIa inhibitors. US patients (n=814) had more diabetes, prior infarction, prior bypass surgery, and renal insufficiency. OUS patients (n=2,788) had longer door-to-balloon times, more radial access, fewer bypass surgeries, and were discharged more often on beta-blockers and statins. At three years US patients had higher mortality (9.7% vs. 6.0%, p=0.0003), reinfarction (10.2% vs. 6.4%, p=0.001), major adverse cardiac events (MACE; 28.2% vs. 20.1%, p<0.0001), major bleeding (16.9% vs. 6.4%, p<0.0001) and net adverse clinical events (NACE; 36.6% vs. 23.8%, p<0.0001), which persisted after adjusting for baseline risk., Conclusions: In the HORIZONS-AMI trial, STEMI patients undergoing primary PCI at US versus OUS sites had higher rates of adverse events, which persisted after adjusting for baseline risk. The reasons for these differences are not clear but may be due to unmeasured confounders, different thresholds for event reporting, or valid differences in systems of care and treatments.

Objectives: The purpose of this study was to evaluate the frequency and predictors of stent thrombosis (ST) after stenting for ST-segment elevation myocardial infarction (STEMI)., Background: Stent thrombosis remains a major concern with STEMI patients treated with primary percutaneous coronary intervention., Methods: Consecutive patients (N = 1,640) undergoing stenting for STEMI were prospectively enrolled in our database and followed for 1 to 15 years. Bare-metal stents were implanted from 1995 to 2002, and drug-eluting and bare-metal stents were implanted from 2003 to 2009. Stent thrombosis was defined as definite or probable., Results: Our population had a high risk profile, including a high incidence of Killip class III to IV (11.5%) and STEMI due to ST (10.2%). Stent thrombosis occurred in 124 patients, including 42 with early ST (0 to 30 days), 35 with late ST (31 days to 1 year), and 47 with very late ST (>1 year). The frequency of ST was 2.7% at 30 days, 5.2% at 1 year, and 8.3% at 5 years. Independent predictors of early or late ST were STEMI due to ST (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.27 to 8.45), small stent size (HR: 2.44, 95% CI: 1.49 to 4.00), Killip class III to IV (HR: 2.39, 95% CI: 1.30 to 4.40), and reperfusion time ≤2 h (HR: 2.09, 95% CI: 1.03 to 4.24). Drug-eluting stent was the only independent predictor of very late ST (HR: 3.73, 95% CI: 1.81 to 7.88)., Conclusions: Stent thrombosis after primary percutaneous coronary intervention is relatively frequent and continues to increase out to 5 years. New strategies are needed to prevent ST in STEMI patients, and targeted therapies are needed in patients identified at highest risk., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Whether thrombus aspiration and local glycoprotein IIb/IIIa administration reduce infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been established in multicenter studies., Design: INFUSE-AMI is a multicenter, open-label, controlled, single-blind randomized study enrolling 452 subjects with anterior STEMI and an occluded proximal or mid-left anterior descending artery with thrombosis in myocardial infarction 0, 1, or 2 grade flow undergoing primary PCI with bivalirudin anticoagulation. Subjects are randomized in a 2 × 2 factorial to one of the following 4 arms: (1) local infusion of abciximab using the ClearWay RX Local Therapeutic Infusion Catheter (ClearWay, Atrium Medical Corp, Hudson, NH) after aspiration with a 6F Export Aspiration Catheter (Medtronic, Inc, Minneapolis, MN), (2) local infusion of abciximab using the ClearWay RX Infusion Catheter and no aspiration, (3) no local infusion of abciximab and aspiration with a 6F Export Aspiration Catheter, or (4) no local infusion of abciximab and no aspiration. The primary end point is infarct size (percentage of total left ventricular mass) at 30 days measured by cardiac magnetic resonance imaging. Other secondary end points include microvascular obstruction by cardiac magnetic resonance imaging at 5 days, ST-segment resolution, angiographic myocardial perfusion, thrombus burden, angiographic complications, and clinical events through 1-year follow-up. Safety end points include major and minor bleeding., Summary: INFUSE-AMI is testing the hypothesis that the intracoronary administration of an abciximab bolus with or without thrombus aspiration before stent implantation compared to no infusion with or without thrombus aspiration reduces infarct size among patients undergoing primary PCI for anterior STEMI who are treated with bivalirudin., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Bleeding events have been associated with adverse early and late outcomes in virtually all clinical settings. The mechanism behind this observation remains poorly understood. We sought to determine if the reason might be the provocation of an inflammatory response by bleeding events. In a formal substudy of the ACUITY trial, plasma samples of a range of biomarkers were collected at baseline, discharge, 30 days, and 1 year from 192 patients with acute coronary syndromes (ACS) and were analyzed in a central core laboratory. Temporal changes in biomarker levels were assessed in patients who experienced in-hospital hemorrhagic events, recurrent ischemic events, or neither. Sixteen patients were excluded from the study (7 with incomplete samples, 5 undergoing coronary artery bypass grafting (CABG) during index hospitalization; 1 had both bleeding and ischemic events). Median high sensitivity C-reactive protein (hs-CRP) levels (mg/l) increased significantly more from admission to discharge among the 9 patients who experienced an in-hospital major bleed compared to either the 9 patients who had a recurrent ischemic event (+6.0 vs. +0.70, P = 0.04) or the 151 patients who had no event (+6.0 vs. +0.60, P = 0.003). Compared to patients with no in-hospital events, median interleukin-6 (IL-6) levels (pg/ml) increased from admission to hospital discharge non-significantly in those with a bleeding event (+0.92 vs. +2.46, P = 0.55) and in those who experienced an in-hospital recurrent ischemic event (+0.92 vs. +3.60, P = 0.09). These data suggest that major bleeding is associated with development of a pro-inflammatory state. If confirmed, this mechanism may in part explain the poor prognosis of patients experiencing an acute hemorrhagic event.

Objectives: The purpose of this study was to assess the frequency of very late stent thrombosis (VLST) after stenting with bare-metal stents (BMS) and drug-eluting stents (DES) for ST-segment elevation myocardial infarction (STEMI)., Background: Stent thrombosis occurs more frequently after stenting for STEMI than after elective stenting, but there are little data regarding VLST., Methods: Consecutive patients (n = 1,463) who underwent stenting for STEMI were prospectively enrolled in our database. BMS were implanted exclusively from 1995 to 2002, and DES and BMS were implanted from 2003 to 2009. Follow-up was obtained at 1 to 15 years., Results: BMS patients (n = 1,095) were older and had more shock, whereas DES patients (n = 368) had more diabetes and smaller vessels. Stent thrombosis occurred in 107 patients, of which 42 were VLST (>1 year). Stent thrombosis continued to increase to at least 11 years with BMS and to at least 4.5 years with DES. Stent thrombosis rates with BMS versus DES were similar at 1 year (5.1% and 4.0%, respectively) but increased more with DES after the first year (1.9%/year vs. 0.6%/year, respectively). Landmark analysis (>1 year) found DES had a higher frequency of VLST (p < 0.001) and reinfarction (p = 0.003). DES was the only significant independent predictor of VLST (hazard ratio: 3.79, 95% confidence interval: 1.64 to 8.79, p = 0.002)., Conclusions: VLST after primary PCI for STEMI occurs with relatively high frequency to at least 11 years with BMS and to at least 4.5 years with DES. Very late stent thrombosis and reinfarction (>1 year) were more frequent with DES. New strategies are needed to manage this problem., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the relationship between 1-year mortality and baseline patient risk in the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial., Background: The HORIZONS-AMI trial showed that bivalirudin compared with unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decreased major bleeding and 30-day and 1-year mortality in patients undergoing primary percutaneous intervention for acute myocardial infarction., Methods: Patients in the HORIZONS-AMI trial were classified as low, intermediate, and high risk according to the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) risk score based on 7 clinical variables., Results: Among 2,530 CADILLAC-score evaluable HORIZONS-AMI trial patients, 1,522 (60%) were classified as low risk, 531 (21%) as intermediate risk, and 477 (19%) as high risk. The mortality rates in the bivalirudin and UFH plus GPI arms, respectively, were 0.4% and 1.2% (p = 0.09) in the low-risk group, 4.2% and 4.1% (p = 0.99) in the intermediate-risk group, and 8.4% and 15.9% (p = 0.01) in the high-risk group. Among high-risk patients, there was also a decreased rate of recurrent myocardial infarction in patients randomized to bivalirudin as compared to UFH plus GPI (3.6% vs. 7.9%, p = 0.04)., Conclusions: In high-risk patients undergoing primary percutaneous coronary intervention for acute myocardial infarction, bivalirudin compared with UFH plus GPI reduces 1-year mortality and recurrent myocardial infarction. (HORIZONS-AMI trial; NCT00433966)., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Our objective was to evaluate the impact of door-to-balloon time (DBT) on mortality depending on clinical risk and time to presentation., Background: DBT affects the mortality rate in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, but the impact may vary across subgroups., Methods: The CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials evaluated stent and antithrombotic therapy in patients undergoing primary percutaneous coronary intervention. We studied the impact of DBT on mortality in 4,548 patients based on time to presentation and clinical risk., Results: The 1-year mortality rate was lower in patients with short versus long DBT (< or = 90 min vs. >90 min, 3.1% vs. 4.3%, p = 0.045). Short DBTs were associated with a lower mortality rate in patients with early presentation (< or = 90 min: 1.9% vs. 3.8%, p = 0.029) but not those with later presentation (>90 min: 4.0% vs. 4.6%, p = 0.47). Short DBTs showed similar trends for a lower mortality rate in high-risk (5.7% vs. 7.4%, p = 0.12) and low-risk (1.1% vs. 1.6%, p = 0.25) patients. Short DBTs had similar relative risk reductions in patients with early presentation in high-risk (3.7% vs. 7.0%, p = 0.08) and low-risk (0.8% vs. 1.5%, p = 0.32) patients, although the absolute benefit was greatest in high-risk patients., Conclusions: Short DBTs (< or = 90 min) are associated with a lower mortality rate in patients with early presentation but have less impact on the mortality rate in patients presenting later. The absolute mortality rate reduction with short DBT is greatest in high-risk patients presenting early. These data may be helpful in designing triage strategies for reperfusion therapy in patients presenting to non-percutaneous coronary intervention hospitals., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the impact of delay to angioplasty in patients with acute coronary syndromes (ACS)., Background: There is a paucity of data on the impact of delays to percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing an invasive management strategy., Methods: Patients undergoing PCI in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial were stratified according to timing of PCI after clinical presentation for outcome analysis., Results: Percutaneous coronary intervention was performed in 7,749 patients (median age 63 years; 73% male) with NSTE-ACS at a median of 19.5 h after presentation (<8 h [n=2,197], 8 to 24 h [n=2,740], and >24 h [n=2,812]). Delay to PCI>24 h after clinical presentation was significantly associated with increased 30-day mortality, myocardial infarction (MI), and composite ischemia (death, MI, and unplanned revascularization). By multivariable analysis, delay to PCI of >24 h was a significant independent predictor of 30-day and 1-year mortality. The incremental risk of death attributable to PCI delay>24 h was greatest in those patients presenting with high-risk features., Conclusions: In this large-scale study, delaying revascularization with PCI>24 h in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes. These findings suggest that urgent angiography and triage to revascularization should be a priority in NSTE-ACS patients., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study compares outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients undergoing saphenous vein graft (SVG) intervention., Background: The safety and efficacy of DES in patients undergoing SVG intervention is controversial., Methods: The STENT (Strategic Transcatheter Evaluation of New Therapies) registry is a multicenter U.S. registry evaluating outcomes with DES. Our study population includes patients undergoing PCI of SVG lesions with DES (n = 785) or BMS (n = 343) who completed 9-month or 2-year follow-up. Outcomes were adjusted with propensity analyses., Results: The DES patients had fewer emergent procedures but had smaller vessels and longer lesions. The DES patients had less death or myocardial infarction at 9 months (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.33 to 0.83, p = 0.006) and less death at 2 years (HR: 0.60, 95% CI: 0.36 to 0.98, p = 0.041). Target vessel revascularization (TVR) was less with DES at 9 months (7.2% vs. 10.0%, HR: 0.36, 95% CI: 0.22 to 0.61, p < 0.001) but was no different by 2 years (18.3% vs. 16.9%, p = 0.86), although adjusted TVR rates were lower (HR: 0.60, 95% CI: 0.40 to 0.90, p = 0.014). The DES reduced TVR at 9 months in SVG lesions with diameter <3.5 mm (8.0% vs. 17.2%, p = 0.013) but not >or=3.5 mm (6.0% vs. 6.6%, p = 0.74)., Conclusions: Treatment of SVG lesions with DES vs. BMS is effective in reducing TVR at 9 months, although most of this advantage is lost at 2 years. The DES seem safe with less death or myocardial infarction, although selection bias might have affected these results. Our data suggest that DES might have short-term advantages over BMS in SVG lesions with diameter <3.5 mm.

The impact of thienopyridine administration prior to primary stenting in acute myocardial infarction (AMI) has not been well studied. We therefore examined the database from the prospective, multicenter, controlled CADILLAC trial in which 1,036 patients were randomized to bare metal stenting with or without abciximab to determine whether patients who received a thienopyridine prior to bare metal stenting in AMI had superior clinical outcomes. Per operator discretion, 659 patients (63.6%; Th+) received either a 500 mg ticlopidine loading dose (n = 623) or a 300 mg clopidogrel loading dose (n = 40), while 377 patients (36.4%; Th-) received no thienopyridine prior to stent implantation. Baseline and procedural characteristics of the two groups, including abciximab use (52.5% vs 52.8%, P = 0.93) were well matched. Th+ compared to Th- patients had lower rates of core lab assessed TIMI 0/1 flow postprocedure (0.8% vs 2.7%, P = 0.01). Th+ compared to Th- patients also had significantly reduced in-hospital and 30-day rates of ischemic target vessel revascularization (TVR) (1.1% vs 3.2%, P = 0.01 and 1.5% vs 3.8%, P = 0.02, respectively) and major adverse cardiovascular events (MACE) (2.7% vs 5.8%, P = 0.01 and 4.0% vs 6.9%, P = 0.03, respectively), results that remained significant after covariate adjustment. In conclusion, in this large prospective, controlled trial, patients receiving a thienopyridine prior to primary stenting in AMI were less likely to have TIMI 0/1 flow postprocedure and experienced reduced in-hospital and 30-day rates of ischemic TVR and MACE compared to those not administered a thienopyridine prior to stent implantation.

Objectives: We sought to determine the relationship between red blood cell (RBC) transfusion and clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI)., Background: The implications of RBC transfusion in patients undergoing primary PCI for AMI have not been evaluated., Methods: Clinical outcomes of patients from the prospective, randomized CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial were analyzed by administration of in-hospital RBC transfusion not related to coronary artery bypass surgery., Results: Of 2,060 randomized patients, 82 (3.98%) received RBC transfusion during the index hospitalization, including 33 (1.60%) with moderate/severe bleeding and 49 (2.38%) without overt major bleeding. Transfusion was independently associated with baseline anemia (odds ratio [95% confidence interval]: 4.44 [2.60 to 7.58], p < 0.0001), older age (1.03 [1.01 to 1.06], p = 0.002), triple-vessel disease (2.54 [1.47 to 4.38], p = 0.0008), and female sex (1.04 [1.02 to 1.06], p = 0.0008). Patients transfused versus not transfused had significantly higher rates of 1-year mortality (23.9% vs. 3.4%), disabling stroke (2.5% vs. 0.5%), reinfarction (7.0% vs. 2.2%), and composite major adverse cardiac events (41.0% vs. 16.6%) (all p values < 0.01). After multivariable adjustment for potential confounders including transfusion propensity, RBC transfusion was independently associated with mortality at 30 days (hazards ratio: 4.71, p = 0.0005) and 1 year (hazards ratio: 3.16, p = 0.0005)., Conclusions: An RBC transfusion after primary PCI in AMI may be harmful, which is consistent with the findings from other studies after PCI in the noninfarct setting. Alternatively, RBC transfusion may be a marker of markedly increased risk. Randomized studies are warranted to determine the optimal threshold for RBC transfusion in patients with AMI undergoing mechanical reperfusion therapy.

Objective: The aim of this article is to examine whether clopidogrel and ticlopidine treatments produce similar clinical outcomes for patients receiving primary stenting for acute myocardial infarction (AMI)., Background: Prior studies have yielded conflicting results on the relative safety and efficacy of clopidogrel and ticlopidine after stent implantation, warranting an evaluation in primary stenting for AMI., Methods: In the multicenter, prospective CADILLAC trial, patients undergoing primary infarct stenting were treated at operator discretion with either ticlopidine (931 patients) or clopidogrel (163 patients) and then followed for 1 year. Baseline clinical and angiographic characteristics were comparable except for baseline TIMI 0/1 flow (72.5% clopidogrel vs. 63.9% ticlopidine, P = 0.04)., Results: Patients receiving clopidogrel had more recurrent ischemia in hospital (6.1 vs. 2.8%, P = 0.02) and at 30 days (10.5 vs. 5.8%, P = 0.02), more moderate and severe bleeding at 30 days (7.4 vs. 2.7%, P = 0.002), and similar rates of stent thrombosis out to 1 year (P = 0.11). By multivariable analysis, clopidogrel use was an independent predictor for recurrent ischemia in hospital (P = 0.0002), and at 30 days (P = 0.012); and of moderate and severe bleeding in hospital (P = 0.002), and at 30 days (P = 0.001)., Conclusions: Despite thienopyridines similarities, their efficacy may be different within the first 30 days of primary stenting for AMI. A prospective, randomized trial is required to confirm these findings., (Copyright 2008 Wiley-Liss, Inc.)

Objectives: This study compares outcomes with drug-eluting stents (DES) versus bare metal stents (BMS) in patients with ST-elevation myocardial infarction (STEMI)., Background: DESs have been effective in elective percutaneous coronary intervention (PCI), but their safety and efficacy in patients with STEMI have not been well studied., Methods: The STENT Registry is a multicenter United States registry evaluating outcomes of DES. Our study population includes patients with STEMI treated with either a DES or BMS who completed 9-month or 2-year follow-up. Outcomes were adjusted using propensity score analysis., Results: DES patients were younger, had less prior infarction and prior bypass surgery, but had smaller vessels and longer lesions. After adjusting for differences in baseline variables, there were no significant differences between DES and BMS in death, reinfarction, or major adverse cardiac events (MACE). DES had lower rates of stent thrombosis at 9 months (1.0% vs. 2.7%, HR 0.40 [0.17-0.95]) and lower rates of target vessel revascularization (TVR) at 9 months (4.0% vs. 7.5%, HR 0.55 [0.34-0.88]) and 2 years (8.0% vs. 11.3%, HR 0.57 [0.35-0.92]). There was a nonsignificant increase in stent thrombosis with DES versus BMS from 1 to 2 years (1.1% vs. 0.3%, P = 0.28)., Conclusions: Our data suggest that DES used with primary PCI for STEMI are more effective than BMS in reducing TVR and are safe for up to 2 years. Whether DES are safe beyond 2 years and whether the reduction in TVR is enough to justify their use in STEMI will have to wait for the results of large randomized trials., (Copyright 2008 Wiley-Liss, Inc.)

Objectives: This study evaluates outcomes and complications in patients treated with drug-eluting stents (DES) for "off-label" indications., Background: Drug-eluting stents have been effective in randomized trials, but their safety and efficacy for off-label indications has not been well studied., Methods: The STENT (Strategic Transcatheter Evaluation of New Therapies) Registry is the largest multicenter U.S. registry evaluating outcomes of DES. Off-label indications included ostial, left main, long, bifurcation, and in-stent restenotic lesions, saphenous vein grafts, chronic total occlusions, small or large vessels, multilesion or multivessel percutaneous coronary interventions, and ST-segment elevation myocardial infarction. Outcomes were adjusted using Cox proportional hazards regression and propensity analyses., Results: Drug-eluting stents were used in an off-label manner in 59% of patients. The patients who received off-label treatment were more often male, had a higher incidence of prior infarction and bypass surgery, and lower ejection fractions. Off-label versus "on-label" use of DES was associated with higher rates of death, myocardial infarction, target vessel revascularization, major adverse cardiac events, and stent thrombosis at 9 months and 2 years. Off-label use of DES compared with off-label use of bare-metal stents (BMS) had lower rates of death, myocardial infarction, target vessel revascularization, and major adverse cardiac events at 9 months and 2 years and lower rates of stent thrombosis at 9 months., Conclusions: Off-label use of DES is associated with higher event rates compared with on-label use of DES, which is consistent with a higher risk clinical and lesion profile. However, event rates with off-label use of DES are lower compared with off-label use of BMS. Pending results from randomized trials, our data support the use of DES for off-label indications in selected patients.

Aims: We sought to investigate the impact of multivessel coronary artery disease (CAD) on reperfusion success and prognosis following primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). The influence of multivessel disease on myocardial reperfusion and subsequent survival after primary PCI has not been studied., Methods and Results: In the CADILLAC trial, primary PCI was performed in 2082 patients of any age with AMI within 12 h of symptom onset. Myocardial perfusion post-PCI assessed by ST-segment recovery and myocardial blush and clinical outcomes were stratified by the extent of CAD. Single-, double-, and triple-vessel disease were present in 1066 (51.2%), 692 (33.2%), and 324 (15.6%) patients, respectively. Patients with multivessel disease compared with those with single-vessel disease undergoing primary PCI were significantly more likely to have absent ST-segment recovery (13.3 vs. 7.4%, P = 0.01), though the rates of post-procedural TIMI-3 flow (89.7 vs. 88.9%, P = 0.66) and grade 2 or 3 myocardial blush (51.2 vs. 51.5%, P = 0.91) in the infarct vessel were comparable. By 1 year, the cumulative incidence of death for patients with single-, double-, and triple-vessel disease was 3.2, 4.4, and 7.8%, respectively (P = 0.003), and the composite rate of major adverse cardiac events (MACE) was 14.8, 19.5, and 23.6%, respectively (P = 0.0006). By multivariable analysis, the presence of triple-vessel disease was the strongest predictor of 1-year death [hazard ratio (HR) = 2.60, P = 0.009], death and re-infarction (HR = 1.88, P = 0.03), and MACE (HR = 1.80, P = 0.0009)., Conclusion: Patients with extensive CAD in vessels remote from the infarct-related artery have reduced reperfusion success and an adverse prognosis following primary PCI in AMI. Future studies regarding the optimal treatment of patients with multivessel disease and AMI are warranted.

The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p=0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.

Background: Thrombus and soft, friable atheromatous plaque are present in the majority of patients with acute myocardial infarction (AMI), and may result in distal embolization and no reflow during primary angioplasty. Thrombectomy prior to intervention may decrease thromboembolic complications and improve outcomes., Methods: The X-TRACT AMI registry was a prospective, multicenter study evaluating the safety and feasibility of the X-Sizer thrombectomy system prior to primary angioplasty in native coronary arteries and saphenous vein grafts (SVGs) in patients presenting within 24 hours AMI onset., Results: A total of 216 patients (220 target lesions) with AMI were enrolled at 28 U.S. sites, with approximately 90% of lesions in native coronary arteries and 10% in SVGs. Preprocedural TIMI 0/1 flow was present in 56% of patients, with thrombus in 76%. Glycoprotein IIb/IIIa inhibitors were used in 86% of patients, and bare metal stents were implanted in 94% (mean stent length 26 mm). TIMI-3 flow was present in 27% of patients at baseline, in 81% after thrombectomy, and in 92% following PCI. Normal myocardial blush grade 3 was present in 6% of patients at baseline, and in 52% postprocedure. At 30 and 360 days, 93.1% and 80.8% of patients were free from major cardiovascular events., Conclusion: In this broad multicenter experience, use of the X-Sizer device prior to stent implantation in thrombus containing native coronary arteries and diseased SVGs was feasible and associated with high rates of normalized postprocedural epicardial blood flow and myocardial blush, warranting further study as an adjunct during primary angioplasty.

We evaluated the utility of a routine postprocedure course of unfractionated heparin after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in patients not receiving glycoprotein IIb/IIIa inhibitors. In the CADILLAC study, 2,082 patients with AMI who underwent primary PCI were randomized to receive stents versus percutaneous transluminal coronary angioplasty (PTCA), each with or without abciximab. In a subset of 976 patients who did not receive abciximab, we compared outcomes of patients who received postprocedural heparin (n = 758; 78%; median duration 2 days) with those who did not. In 421 patients treated with PTCA, postprocedural heparin use was associated with lower in-hospital major adverse cardiac events (MACEs; 5.3% vs 11.4%, p = 0.069), 1-year MACEs (22% vs 31%, p = 0.08), and decreased in-hospital moderate/severe bleeding (2.3% vs 8.9%, p = 0.01). By multivariate analyses, heparin use correlated with freedom from in-hospital and 1-year MACEs in patients after PTCA. In contrast, in 555 patients who underwent stenting, postprocedural heparin use was associated with increased bleeding and hospitalization costs without a decrease in early or late MACEs. In conclusion, in patients with AMI treated with coronary stenting without glycoprotein IIb/IIIa inhibitors, routine postprocedural heparin was not associated with any significant benefits and may be safely omitted. However, in a subset of patients treated with PTCA, postprocedural heparin use was independently associated with fewer in-hospital and 1-year MACEs.

We determined the outcomes of patients with acute ST-segment elevation (STE) myocardial infarction (STEMI) and non-STEMI (NSTEMI) after primary percutaneous coronary intervention (PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for > 30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725 (87.8%) and NSTEMI in 239 (12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival (2.4 vs 1.8 hours, p = 0.0002) and increased door-to-balloon time (3.2 vs 1.9 hours, p < 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline (37.3% vs 19.4%, p < 0.0001) and higher ejection fraction (58.7% vs 55.8%, p = 0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality (3.4% vs 4.4%, p = 0.40) but higher rates of major adverse cardiac events (24.0% vs 16.6%, p = 0.007) that was driven by more frequent ischemic target vessel revascularization (21.8% vs 11.9%, p <0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.

Background: The association between infarct artery location, reperfusion success, and clinical outcomes after primary percutaneous coronary intervention (PCI) has not been characterized. We examined the infarct artery-specific impact of epicardial and myocardial flow and reperfusion after primary PCI for acute myocardial infarction., Methods: Among 2082 patients undergoing primary PCI in the CADILLAC trial, myocardial blush grade, TIMI flow grade, ST-segment resolution, and clinical outcomes were analyzed according to the infarct artery., Results: Baseline clinical characteristics did not significantly differ between patients experiencing infarction in the left anterior descending (LAD, 37%) versus left circumflex (18%) and right coronary artery (46%) distributions. Baseline left ventricular function was reduced, and collateral flow was less commonly present in patients with infarction involving the LAD. Achievement of final TIMI-3 flow, grade 3 myocardial blush, and ST-segment resolution >70% was also significantly less common in anterior infarction. Patients with anterior versus nonanterior infarction had significantly higher mortality at 30 days (3.4% vs 1.3%, P = .0006) and 1 year (6.5% vs 2.9%, P < .0001) and had increased 1-year rates of reinfarction (3.6% vs 1.7%, P = .009) and ischemic target vessel revascularization (16.1% vs 11.7%, P = .006). By multivariate analysis, LAD infarction was a powerful independent predictor of 1-year mortality (odds ratio 2.45, P = .009)., Conclusions: Acute myocardial infarction involving the LAD distribution is associated with reduced left ventricular function, less frequent collateral flow, impaired myocardial perfusion and decreased reperfusion success, findings associated with reduced survival, and increased major adverse cardiac events compared with other vascular territories. These data provide mechanistic insights to the adverse prognosis of patients with anterior infarction.

Background: The prognostic importance of obesity after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) is unknown. We therefore sought to investigate the impact of body mass index (BMI) in patients with AMI undergoing primary PCI., Methods: In the CADILLAC trial, 2082 patients of any age with AMI within 12 hours onset undergoing primary PCI were randomized to balloon angioplasty versus stenting, each +/-abciximab. Outcomes were stratified by baseline BMI., Results: Baseline BMI was measured in 2035 (98%) randomized patients; 552 (27%) patients have normal weight (BMI < 25 kg/m2), 915 (45%) were overweight (> or = 25 to < 30 kg/m2), and 568 (28%) were obese (> or = 30 kg/m2). Compared with normal-weight patients, obese patients were younger and more frequently had diabetes, hyperlipidemia, hypertension, non-anterior myocardial infarction, and higher creatinine clearance. Obese patients were less likely to develop thrombocytopenia (1.8% vs 4.2%), moderate hemorrhagic complications (1.4% vs 3.3%), or required blood product transfusions (3.2% vs 6.3%) (all P < or = .04). Obese compared with normal-weight patients had lower inhospital mortality (0.9% vs 2.7%, P = .03) at 30 days (1.1% vs 3.8%, P = .02) and 1 year (1.8% vs 7.5%, P < .0001). Independent predictors of 30-day and 1-year mortality included lower ejection fraction, advanced age, 3-vessel disease, anterior AMI, and lower creatinine clearance, but not BMI., Conclusions: Obese patients with AMI have an improved prognosis after primary PCI compared with normal-weight patients, a finding attributable to AMI onset at younger age, with better renal function and less anterior infarction.

We examined the effect of aspirin use at the time of admission and discharge from a large-scale, prospective multicenter trial of patients who had been treated with primary percutaneous coronary intervention in acute myocardial infarction.

We sought to identify the predictors and clinical outcomes of early thrombosis after primary angioplasty and stenting for acute myocardial infarction (AMI). Little is known about the correlates and prognosis of acute and subacute thromboses after percutaneous coronary intervention (PCI) for AMI. We therefore studied the frequency, clinical determinants, and implications of early thrombosis in a large trial of patients who had primary PCI. In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications trial, 2,082 patients who had AMI were randomized in a 2 x 2 factorial design to primary stenting or to balloon angioplasty, each with and without abciximab. Early thrombosis occurred in 19 patients (0.9%) at a median of 2 days (range 0 to 23). Maximal balloon diameter was smaller, and aneurysmal and bifurcation lesions were more prevalent in the group with early thrombosis. Early thrombosis occurred in 0.4% of patients who had been randomized to receive abciximab versus 1.5% of control patients (p <0.01) and in 0.5% of patients who had been randomized to undergo stenting versus 1.4% of those who underwent balloon angioplasty (p = 0.04). By multivariate analysis, abciximab use was an independent predictor of no thrombosis (hazard ratio 0.27, 95% confidence interval 0.09 to 0.86, p = 0.026). Within 30 days, 5.3% of patients who had early thrombosis died, 32.9% developed reinfarction, and 89.5% required repeat target vessel revascularization (including bypass surgery in 11.1%). As a result, patients who had versus those who did not have early thrombosis had markedly higher rates of major adverse cardiac events at 30 days (94.7% vs 5.0%, p <0.0001) and at 1 year (94.7% vs 16.9%, p <0.0001). Patients who develop early thrombosis after primary PCI have a very high rate of major adverse cardiac events, including death and reinfarction, and usually require repeat coronary angioplasty or surgery for management. Complex baseline angiographic morphology and smaller maximal balloon diameter are predictors of early thrombosis after primary PCI for AMI. The incidence of early thrombosis after primary angioplasty and stenting is decreased by abciximab use.

Background: Biological age is a strong determinant of prognosis in patients with acute myocardial infarction (AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty., Methods and Results: In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty, angioplasty plus abciximab, stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age (1.6% for patients <55 years, 2.1% for 55 to 65 years, 7.1% for 65 to 75 years, 11.1% for patients >75 years; P<0.0001). Elderly patients also had increased rates of stroke and major bleeding compared with their younger counterparts. Among elderly patients (> or =65 years), 1-year rates of ischemic target revascularization (7.0% versus 17.6%; P<0.0001) and subacute or late thrombosis (0% versus 2.2%; P=0.005) were reduced with stenting compared with balloon angioplasty. Routine abciximab administration, although safe, was not of definite benefit in elderly patients. Rates of mortality, reinfarction, disabling stroke, and major bleeding in the elderly were independent of reperfusion modality., Conclusions: Despite contemporary mechanical reperfusion strategies, mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein IIb/IIIa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI.

Objective: This study was done to assess and compare the prognostic significance of multiple methods for measuring ST-segment elevation resolution (STR) following primary percutaneous coronary intervention (PCI)., Background: Resolution of ST-segment elevation (STE) is a powerful predictor of both infarct-related artery patency and mortality in acute myocardial infarction (AMI). Recent thrombolytic studies have suggested that simple measures of STR may be as powerful as more complex algorithms. The optimal method of assessing STR following primary PCI has not been studied., Methods: We analyzed 700 patients with technically adequate baseline and post-PCI electrocardiograms from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Five methods were used to assess STR: 1) summed %STR across multiple leads (SigmaSTR); 2) %STR in the single lead with maximum baseline STE (MaxSTR); 3) absolute maximum STE before the procedure; 4) absolute maximum STE after intervention (MaxSTPost); and 5) a categorical variable based upon MaxSTPost (High Risk)., Results: At 30 days, SigmaSTR, MaxSTR, and MaxSTPost all correlated strongly with mortality (p = 0.004, p = 0.005, and p < 0.0001, respectively) and the combined end point of mortality or reinfarction (p = 0.001, p = 0.001, and p < 0.0001). At one year, SigmaSTR and MaxSTPost correlated with mortality (p = 0.04, p = 0.0001), reinfarction (p = 0.02, p = 0.0015), and the combined end point (p = 0.02, p < 0.0001). By multivariate analysis, only the simpler measures of MaxSTPost and High Risk categorization independently predicted all outcomes at both time points., Conclusions: The STR following primary PCI in AMI correlates strongly with mortality and reinfarction, independent of target vessel patency. The simple measure of the maximal residual degree of STE after primary PCI is a strong independent predictor of both survival and freedom from reinfarction at 30 days and 1 year.

Objectives: We sought to investigate the impact of anemia in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI)., Background: The prognostic importance of anemia on primary PCI outcomes is unknown., Methods: In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, 2,082 patients of any age with AMI within 12 h onset undergoing primary PCI were randomized to balloon angioplasty versus stenting, each +/- abciximab. Outcomes were stratified by the presence of anemia at baseline, as defined by World Health Organization criteria (hematocrit <39% for men and <36% for women)., Results: Anemia was present in 260 (12.8%) of 2,027 randomized patients with baseline laboratory values. Patients with versus without baseline anemia more frequently developed in-hospital hemorrhagic complications (6.2% vs. 2.4%, p = 0.002), had higher rates of blood product transfusions (13.1% vs. 3.1%, p < 0.0001), and had a prolonged (median 4.1 vs. 3.5 days, p < 0.0001) and more expensive (median costs $12,434 vs. $11,603, p = 0.002) index hospitalization. Patients with versus without anemia had strikingly higher mortality during hospitalization (4.6% vs. 1.1%, p = 0.0003), at 30 days (5.8% vs. 1.5%, p < 0.0001), and at 1 year (9.4% vs. 3.5%, p < 0.0001). The rates of disabling stroke at 30 days (0.8% vs. 0.1%, p = 0.005) and at 1 year (2.1% vs. 0.4%, p = 0.0007) were also significantly higher in patients with anemia. By multivariate analysis, anemia was an independent predictor of in-hospital mortality (hazard ratio, 3.26; p = 0.048) and one-year mortality (hazard ratio, 2.38; p = 0.016)., Conclusions: Anemia at baseline in patients with AMI undergoing primary PCI is common, and is strongly associated with adverse outcomes and increased mortality.

Objectives: We sought to determine the prognostic importance of myocardial reperfusion after various contemporary interventional strategies in patients with acute myocardial infarction (AMI)., Background: The frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty in AMI have not been examined in a large-scale prospective study. Similarly, whether glycoprotein (GP) IIb/IIIa inhibitors and/or stents improve myocardial perfusion beyond balloon angioplasty has not been investigated., Methods: Tissue-level perfusion assessed by the myocardial blush grade was evaluated in 1,301 patients with AMI randomized to balloon angioplasty versus stenting, each with or without abciximab., Results: Despite Thrombolysis In Myocardial Infarction flow grade 3 restoration in 96.1% of patients, myocardial perfusion was normal in only 17.4% of patients, reduced in 33.9%, and absent in 48.7%. Myocardial perfusion status post-coronary intervention stratified patients into three distinct risk categories, with 1-year mortality rates of 1.4% (normal blush), 4.1% (reduced blush), and 6.2% (absent blush) (p = 0.01). Among patients randomized to angioplasty, angioplasty + abciximab, stenting, and stenting + abciximab, normal myocardial perfusion was restored in 17.7%, 17.0%, 17.5%, and 17.6%, respectively (p = 0.95), which was associated with similar 1-year rates of mortality in patients randomized to stenting versus angioplasty (4.5% vs. 4.8%, p = 0.91) and abciximab versus no abciximab (4.3% vs. 5.0%, p = 0.63)., Conclusions: Restoration of normal tissue-level perfusion is a powerful determinate of survival after primary PCI in AMI and is achieved in a minority of patients. Neither stents nor GP IIb/IIIa inhibitors significantly enhance myocardial perfusion compared to balloon angioplasty alone, underlying the similar long-term mortality with these different mechanical reperfusion strategies.

Objectives: We sought to determine the prognostic importance of mitral regurgitation (MR) in patients undergoing percutaneous coronary intervention for acute myocardial infarction (AMI)., Background: Mitral regurgitation has been associated with a poor prognosis in patients treated with thrombolytic therapy for AMI. The prognostic significance of MR in patients undergoing mechanical reperfusion therapy for AMI is unknown., Methods: Left ventriculography was performed during the index procedure in 1,976 (95%) of 2,082 non-shock patients enrolled in a prospective, multicenter, randomized trial of mechanical reperfusion strategies in AMI. The severity of operator-assessed MR was divided into four strata: none (n = 1,726), mild (n = 192), and moderate/severe (n = 58)., Results: Patients with progressively more severe MR were older (p < 0.0001), were more often women (p < 0.0001), and had higher Killip class (p = 0.0007). More severe grades of MR correlated with triple-vessel disease (p < 0.0001) and lower left ventricular ejection fraction (LVEF) as measured during the index procedure (p = 0.0004). Increasingly severe MR was strongly associated with a higher mortality at 30 days (1.4% vs. 3.7% vs. 8.6%, respectively; p < 0.0001) and at one year (2.9%, 8.5%, 20.8%, respectively; p < 0.0001). By multivariate analysis, the presence of even mild MR was an independent predictor of long-term mortality (mild MR, relative risk [RR] = 2.40, p = 0.005; moderate/severe MR, RR = 2.82, p = 0.006)., Conclusions: Mitral regurgitation of any degree present on the baseline left ventriculogram during the index procedure is a powerful, independent predictor of mortality in patients undergoing mechanical reperfusion therapy for AMI. The presence of MR identifies high-risk patients in whom close out-patient follow-up is warranted, and who may benefit from aggressive adjunctive medical or surgical therapies.

Background: Both stenting and the glycoprotein IIb/IIIa inhibitor abciximab improve outcomes for patients undergoing primary angioplasty for acute myocardial infarction (AMI). However, the cost-effectiveness of these strategies is unknown., Methods and Results: We performed a prospective cost-utility analysis among US participants in the CADILLAC trial. Patients with AMI (n=1703) were randomized to stenting versus balloon angioplasty (PTCA) and abciximab versus no abciximab according to a 2-by-2 factorial design. Total 1-year costs and lifetime incremental cost-effectiveness ratios, measured as cost per quality-adjusted year of life (QALY) gained, were calculated. Compared with PTCA, stenting increased procedural costs by 1148 dollars and initial hospital costs by 1384 dollars (both P<0.001). By 1-year, stenting led to fewer repeat revascularization procedures and reduced follow-up medical care costs by 1215 dollars, such that aggregate costs were similar for the PTCA and stent groups (18 690 dollars versus 18 859 dollars, P=0.75). The cost-effectiveness ratio for stenting versus PTCA was favorable at 11 237 dollars/QALY gained and remained <20 000 dollars/QALY in sensitivity analyses. Compared with standard anticoagulation, abciximab increased initial procedural costs by 1122 dollars (P<0.001). By facilitating accelerated hospital discharge, abciximab reduced length of stay by approximately 0.6 days, offsetting most of the drug costs. These cost offsets were not maintained, however; aggregate 1-year costs for the abciximab group were 1244 dollars greater than for standard therapy (19 389 dollars versus 18 145 dollars , P=0.02). Abciximab was reasonably cost-effective (cost-effectiveness ratio 21 305 dollars/QALY) only if nonsignificant differences in 1-year mortality (3.7% versus 4.3%, P=0.62) were incorporated in the analysis., Conclusions: Primary stenting is a highly cost-effective treatment for AMI. The cost-effectiveness of abciximab in this setting is uncertain and depends primarily on whether long-term survival is enhanced.

The results of bail-out stenting after unsuccessful primary balloon angioplasty compared with routine stenting or successful balloon angioplasty in acute myocardial infarction are unknown. In the CADILLAC trial, 168 of 1,044 patients (16.1%) randomized to balloon angioplasty crossed over to stenting after unsuccessful dilatation. Event-free survival was similar after bail-out and routine stenting, and was greater than after successful balloon angioplasty.

The utility of glycoprotein IIb/IIIa receptor inhibitors as a "bail-out" modality after unsuccessful primary percutaneous coronary intervention for acute myocardial infarction is unknown. In the CADILLAC trial, of 1,030 control patients, 62 patients (6.0%) crossed over and received abciximab for procedural complications or suboptimal angioplasty results. Compared with patients who received routine upfront abciximab, those treated with bail-out abciximab had markedly lower rates of Thrombolysis In Myocardial Infarction grade 3 flow and increased rates of hemorrhagic and ischemic complications at 30 days and 1 year.