Interaction Between Race and Income on Cardiac Outcomes After Percutaneous Coronary Intervention.

Background Compared with White Americans, Black Americans have a greater prevalence of cardiac events following percutaneous coronary intervention. We evaluated the association between race and neighborhood income on post-percutaneous coronary intervention cardiac events and assessed whether income modifies the effect of race on this relationship. Methods and Results Consecutive patients (n=23 822) treated with percutaneous coronary intervention from January 1, 2000, to December 31, 2016, were included. All-cause mortality and major adverse cardiac event were assessed at 3 years. Extended 10-year follow-up was performed for those residing locally (n=1285). Neighborhood income was derived using median adjusted annual gross household income reported within the patient's zip code. We compared differences in treatment and outcomes, adjusting for race, income, and their interaction. In total, 3173 (13.3%) patients self-identified as Black Americans, and 20 649 (86.7%) self-identified as White Americans. Black Americans had a worse baseline cardiac risk profile and lower neighborhood income compared with White Americans. Although risk profile improved with increasing income in White Americans, no difference was observed across incomes among Black Americans. Despite similar long-term outpatient cardiology follow-up and medication prescription, risk profiles among Black Americans remained worse. At 3 years, unadjusted all-cause mortality (18.0% versus 15.2%; P<0.001) and major adverse cardiac event (37.3% versus 34.6%; P<0.001) were greater among Black Americans and with lower income (both P<0.001); race, income, and their interaction were not significant predictors in multivariable models. At 10-year follow-up, increasing income was associated with improved outcomes only in White Americans but not Black Americans. In multivariable models for major adverse cardiac event, income (hazard ratio [HR], 0.97 [95% CI, 0.96-0.98]; P=0.005), Black race (HR, 1.77 [95% CI, 1.58-1.96]; P=0.006), and their interaction (HR, 0.98 [95% CI, 0.97-0.99]; P=0.003) were significant predictors. Similar findings were observed for cardiac death. Conclusions Early 3-year post-percutaneous coronary intervention outcomes were driven by worse risk factor profiles in both Black Americans and those with lower neighborhood income. However, late 10-year outcomes showed an independent effect of race and income, with improving outcomes with greater income limited to White Americans. These findings illustrate the importance of developing novel care strategies that address both risk factor modification and social determinants of health to mitigate disparities in cardiac outcomes.

Five years of a comprehensive ST-elevation myocardial infarction protocol and its association with sex disparities.

Aims: To determine whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol is associated with reduced sex disparities over 5 years. Methods and results: This was an observational cohort study of 1833 consecutive STEMI patients treated with percutaneous coronary intervention (PCI) before (1 January 2011-14 July 2014, control group) and after (15 July 2014-15 July 2019, protocol group) implementation of a protocol for early guideline-directed medical therapy (GDMT), rapid door to balloon time (D2BT), and use of trans-radial PCI. In the control group, females had less GDMT (77.1% vs. 68.1%, P = 0.03), similarly low trans-radial PCI (19.0% vs. 17.6%, P = 0.73), and longer D2BT [104 min (79, 133) vs. 112 min (85, 147), P = 0.02] corresponding to higher in-hospital mortality [4.5% vs. 10.3%, odds ratio (OR) 2.44 (1.34-4.46), P = 0.004], major adverse cardiac and cerebrovascular events [MACCE, 9.8% vs. 16.3%, OR 1.79 (1.14-2.84), P = 0.01], and net adverse clinical events [NACE, 16.1% vs. 28.3%, OR 2.06 (1.42-2.99), P < 0.001]. In the protocol group, no significant sex differences were observed in GDMT (87.2% vs. 86.4%, P = 0.81) or D2BT [85 min (64-106) vs. 89 min (65-111), P = 0.06], but trans-radial PCI was used less in females (77.6% vs. 71.2%, P = 0.03). In-hospital mortality [2.5% vs. 4.4%, OR 1.78 (0.91-3.51), P = 0.09] and MACCE [9.0% vs. 11.1%, OR 1.27 (0.83-1.92), P = 0.26] were similar between sexes, but higher NACE in females approached significance [14.8% vs. 19.4%, OR 1.38 (0.99-1.92), P = 0.05] due to higher bleeding risk [7.2% vs. 11.1%, OR 1.60 (1.04-2.46), P = 0.03]. Conclusions: A comprehensive STEMI protocol was associated with sustained reductions for in-hospital ischaemic outcomes over 5 years, but higher bleeding rates in females persisted.

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided pnon-inferiority=0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided pnon-inferiority=0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20·3%) patients assigned to BVS and 274 (20·5%) patients assigned to EES (difference -0·3%, 95% CI -3·4% to 2·9%; one-sided pnon-inferiority=0·0008; two-sided psuperiority=0·8603). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.

Recognized Obstructive Sleep Apnea is Associated With Improved In-Hospital Outcomes After ST Elevation Myocardial Infarction.

BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for many cardiovascular conditions such as coronary artery disease, myocardial infarction, systemic hypertension, pulmonary hypertension, and stroke. However, the association of OSA with outcomes in patients hospitalized for ST-elevation myocardial infarction remains controversial. METHODS AND RESULTS: We used the nation-wide inpatient sample between 2003 and 2011 to identify patients with a primary discharge diagnosis of ST-elevation myocardial infarction and then used the International Classification of Diseases, Clinical Modification code 327.23 to identify a group of patients with OSA. The primary outcome of interest was in-hospital mortality, and secondary outcomes were in-hospital cardiac arrest, length of stay and hospital charges. Our cohort included 1 850 625 patients with ST-elevation myocardial infarction, of which 1.3% (24 623) had documented OSA. OSA patients were younger and more likely to be male, smokers, and have chronic pulmonary disease, depression, hypertension, known history of coronary artery disease, dyslipidemia, obesity, and renal failure (P<0.001 for all). Patients with OSA had significantly decreased in-hospital mortality (adjusted odds ratio, 0.78 [95% CI, 0.73-0.84]), longer hospital stay (5.00±4.68 versus 4.85±5.96 days), and incurred greater hospital charges ($79 460.12±70 621.91 versus $62 889.91±69 124.15). There was no difference in incidence of in-hospital cardiac arrest (adjusted odds ratio, 0.93 [95% CI, 0.84-1.03]) between these 2 groups. CONCLUSION: ST-elevation myocardial infarction patients with recognized OSA had significantly decreased mortality compared with patients without OSA. Although patients with OSA had longer hospital stays and incurred greater hospital charges, there was no difference in incidence of in-hospital cardiac arrest.

Economic Outcomes of Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: 1-Year Results From the ABSORB III Trial.

OBJECTIVES: The purpose of this study was to evaluate the economic impact of the Absorb bioresorbable vascular scaffold compared with the Xience everolimus-eluting stent in patients undergoing percutaneous coronary intervention. BACKGROUND: The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to the Xience stent with respect to target lesion failure at 1 year. Whether health care costs differ between the Absorb scaffold and the Xience stent is unknown. METHODS: We performed a prospective health economic study alongside the ABSORB III trial, in which patients undergoing percutaneous coronary intervention for stable or unstable angina were randomized to receive the Absorb scaffold (n = 1,322) or Xience stent (n = 686). Resource use data were collected through 1 year of follow-up. Costs were assessed using resource-based accounting (for procedures), MedPAR data (for other index hospitalization costs), and Medicare reimbursements (for follow-up costs and physician fees). RESULTS: Initial procedural costs were higher with the Absorb scaffold than the Xience stent ($6,316 ± 1,892 vs. $6,103 ± 1,895; p = 0.02), driven mainly by greater balloon catheter use and the higher cost of the scaffold in the Absorb group. Nonetheless, index hospitalization costs ($15,035 ± 2,992 for Absorb vs. $14,903 ± 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 ± 6,110 for Absorb vs. $17,498 ± 7,411 for Xience; p = 0.29) were similar between the 2 groups. CONCLUSIONS: Although initial procedural costs were higher with the Absorb scaffold, there were no differences in total 1-year health care costs between the 2 cohorts. Longer term follow-up is needed to determine whether meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation of Absorb™ BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906).

Impact of lean six sigma process improvement methodology on cardiac catheterization laboratory efficiency.

BACKGROUND: Operational inefficiencies are ubiquitous in several healthcare processes. To improve the operational efficiency of our catheterization laboratory (Cath Lab), we implemented a lean six sigma process improvement initiative, starting in June 2010. We aimed to study the impact of lean six sigma implementation on improving the efficiency and the patient throughput in our Cath Lab. METHODS: All elective and urgent cardiac catheterization procedures including diagnostic coronary angiography, percutaneous coronary interventions, structural interventions and peripheral interventions performed between June 2009 and December 2012 were included in the study. Performance metrics utilized for analysis included turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start and manual sheath-pulls inside the Cath Lab. RESULTS: After implementation of lean six sigma in the Cath Lab, we observed a significant improvement in turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start as well as sheath-pulls inside the Cath Lab. The percentage of cases with optimal turn-time increased from 43.6% in 2009 to 56.6% in 2012 (p-trend<0.001). Similarly, the percentage of cases with an aggregate on-time start increased from 41.7% in 2009 to 62.8% in 2012 (p-trend<0.001). In addition, the percentage of manual sheath-pulls performed in the Cath Lab decreased from 60.7% in 2009 to 22.7% in 2012 (p-trend<0.001). CONCLUSIONS: The current longitudinal study illustrates the impact of successful implementation of a well-known process improvement initiative, lean six sigma, on improving and sustaining efficiency of our Cath Lab operation. After the successful implementation of this continuous quality improvement initiative, there was a significant improvement in the selected performance metrics namely turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start as well as sheath-pulls inside the Cath Lab.

Utility of Glycated Hemoglobin for Assessment of Glucose Metabolism in Patients With ST-Segment Elevation Myocardial Infarction.

Glycated hemoglobin (HbA1c) is an approved and widely used laboratory investigation for diagnosis of diabetes that is not affected by acute changes in blood glucose. Our aim was to analyze the extent to which routine HbA1c measurements diagnose unknown diabetes mellitus (DM) in patients presenting with ST-segment elevation myocardial infarction (STEMI). We also compared outcomes in patients with newly diagnosed DM, previously established DM and those without DM. Consecutive patients undergoing PCI for STEMI from January 2005 to December 2012 were included and routinely performed admission HbA1c was used to identify patients with previously undiagnosed DM (HbA1c ≥6.5 and no history of DM or DM therapy) and pre-DM (HbA1c 5.7% to 6.4%). Overall 1,686 consecutive patients underwent primary percutaneous coronary intervention for STEMI during the study period and follow-up data were available for 1,566 patients (90%). A quarter of the patients (24%, n = 405) had history of DM, 7% (n = 118) had previously undiagnosed DM, and 38.7% (n = 652) had pre-DM. Mortality was comparable in patients with known DM and newly diagnosed DM both in-hospital (11.1% vs 11.9%, p = 0.87) and at 3-year follow-up (27.3% and 24%). Patients with DM, including those who were newly diagnosed, had higher mortality at 3 years (26.5%) compared to those with pre-DM (12.1%) or no dysglycemia (11.2%, p <0.01). In conclusion, a substantial number of patients with STEMI have previously undiagnosed DM (7%). These patients have similar in-hospital and long-term mortality as those with known DM, and outcomes are inferior to patients without dysglycemia.

Length of stay and long-term mortality following ST elevation myocardial infarction.

BACKGROUND: Over the last few decades, there has been a significant reduction in hospital length of stay (LOS) among patients undergoing percutaneous intervention (PCI) for ST elevation myocardial infarction (STEMI). Although studies have looked at predictors of long hospital stay after STEMI, the impact of LOS on long-term outcomes after PCI remains unknown. We aimed to evaluate the association between LOS at the time of index hospitalization for PCI and long-term mortality among patients presenting with STEMI. METHODS: We examined all patients undergoing PCI for STEMI at the Cleveland Clinic Catheterization Laboratory between 2002 and 2011. Long-term all-cause mortality was assessed using the Social Security Death Index and electronic medical record review. LOS was extracted from the discharge summary of the index hospitalization. RESULTS: A total of 1,963 patients were included in the study. Of these 1,963 patients undergoing PCI for STEMI, 126 (6.4%) died during the index hospitalization. Among survivors of this hospitalization, we observed a significant increase in long-term mortality with an increase in LOS during index hospitalization (P < 0.001). Adjustment for demographic and clinical characteristics yielded statistically significant increased mortality among patients with LOS of 6-10 days [HR (95% CI): 2.2 (1.3-3.5)] and LOS > 10 days [HR (95% CI): 2.6 (1.6-4.3)], in comparison with patients with LOS of 1-2 days. CONCLUSIONS: Long hospital stay after PCI among patients with STEMI was associated with an increased long-term mortality. A long hospital stay may be used as a marker to identify patients at higher risk for long-term mortality.

Prognostic value of estimated functional capacity incremental to cardiac biomarkers in stable cardiac patients.

BACKGROUND: Few studies have investigated functional capacity self-assessment tools in either prediction of future major adverse cardiac outcomes beyond all-cause mortality or direct comparisons with clinically available biomarkers. METHODS AND RESULTS: We estimated functional capacity using the Duke Activity Status Index (DASI) questionnaire in 8987 sequential stable patients without acute coronary syndrome who were undergoing elective diagnostic coronary angiography with 3-year follow-up of major adverse cardiac events (death, nonfatal myocardial infarction, or stroke). A low DASI score provided independent prediction of a 4.8-fold increase in future risk of incident major adverse cardiac events at 3 years (quartiles 1 versus 4 hazard ratio [95% CI] 4.76 [4.03 to 5.61], P<0.001), and a 3.8-fold increased risk after adjusting for traditional risk factors (3.77 [3.15 to 4.51], P<0.001). The prognostic value of the DASI score was evident in both primary and secondary prevention cohorts, with and without heart failure, as well as high and low C-reactive protein and B-type natriuretic peptide levels. The DASI score reclassified 15% of patients (P<0.001) beyond traditional risk factors in predicting future MACE. CONCLUSION: A simple self-assessment tool of functional capacity in stable patients undergoing elective diagnostic cardiac evaluation provides independent and incremental prognostic value for prediction of both significant coronary angiographic disease and long-term adverse clinical events.

Impact of diabetes on long-term mortality following multivessel percutaneous interventions: an insight into optimal statistical analysis.

BACKGROUND: Several studies have demonstrated better long-term outcomes with drug eluting stents (DES) as compared to bare metal stents (BMS) among diabetics with coronary artery disease (CAD). A significant heterogeneity exists with respect to the optimal statistical strategy to analyze stent related data. METHODS: We used our percutaneous intervention (PCI) registry to identify all diabetics with CAD, who underwent PCI on two or more vessel territories between 2003 and 2009. Long-term mortality was assessed using the social security death index. Six different analytical strategies were applied. RESULTS: A total of 1568 DES and 336 BMS interventions were encountered in 756 diabetics. Considerable differences were observed in the results between the methods applied. Generalized estimating equation (GEE) approach with an autoregressive correlation structure (GEE) was a robust method to account for the cluster structure, since the measurements taken through time on the same person were assumed to be highly correlated, if they were spaced more closely in time. Diabetics undergoing PCI with BMS had a significantly higher long-term mortality as compared to the patients undergoing DES-PCI [Hazard ratio (95% CI): 1.47 (1.04-2.09)]. CONCLUSION: There is a great potential for erroneous interpretation of PCI data due to complex spatial and temporal clustering. Use of GEE with autoregressive correlation matrix and robust variance is most optimal to account for the clustered nature of the PCI related data. Using GEE, we observed that there is a 47% (4%-119%) higher hazard for mortality among diabetics undergoing BMS-PCI as compared to diabetics undergoing DES-PCI.

Percutaneous coronary revascularization in coronary artery disease: lessons from a single center experience.

OBJECTIVES: To determine the role of percutaneous coronary intervention (PCI) and its impact on mortality in coronary artery disease (CAD). BACKGROUND: It's unclear whether PCI provides benefit in patients with CAD outside of acute settings. We sought to determine the role of PCI and its effect on mortality in patients with similar entry criteria to prior RCTs and compare outcomes with medical treatment. METHODS: Using institutional diagnostic catheterization database of consecutive patients undergoing coronary angiography from 1/2004 to 1/2010, we examined records for patients with a positive stress test and >70% coronary stenosis or symptoms of angina and >80% coronary stenosis. We excluded those with acute coronary syndromes, low ejection fraction (EF), history of CABG, and CABG following index catheterization. We stratified patients by treatment and performed unadjusted and propensity matched analyses. The outcome was all-cause mortality obtained from the social security death index. RESULTS: We identified 3,375 patients using study inclusion criteria. Mean age was 65 ± 11 years and 69% (n = 2,332) were men. Mean EF was 55% ± 8%. In the unadjusted cohort, 1,265 patients received medical management and 2,110 received PCI. The unadjusted analysis revealed significantly better survival in PCI patients (P < 0.0001) (HR: 0.51; 95% confidence interval (CI), 0.41-0.63). Propensity matching was performed for 1,580 patients and analysis showed better survival among patients receiving PCI (0 = 0.04) (HR: 0.74; 95% CI, 0.55-0.98). PCI continued to show better survival after excluding patients with malignancy (P = 0.03) and unstable angina (P = 0.007). CONCLUSIONS: This single center registry analysis demonstrated better survival in stable CAD patients undergoing PCI compared to medical management alone. These data suggest there may be a benefit of PCI beyond symptom relief. Future randomized trials are needed to further understand the role of PCI in broader patient populations.

Stent choice and the hidden consequences of cost savings.

Amin and colleagues have attempted to estimate the cost savings to the US health-care system if drug-eluting coronary stents were more selectively used in patients at low risk of restenosis. Their results and conclusions raise statistical, societal, and ethical issues that need to be considered before this approach should be widely embraced.

Comparison of outcomes of unprotected left main versus multivessel coronary artery interventions.

Left main coronary artery (LMCA) percutaneous coronary intervention (PCI) has emerged as an appealing alternative to bypass surgery for significant LMCA disease, especially in high-risk candidates. PCI for unprotected LMCA stenosis is currently designated a class IIb indication. Direct comparisons between unprotected LMCA PCI and multivessel PCI are lacking. We aimed to determine the incremental risk associated with unprotected LMCA PCI compared to multivessel PCI. We queried the Cleveland Clinic PCI database to identify patients who underwent unprotected LMCA PCI from 2003 through 2009 and compared these to patients undergoing multivessel PCI in the same period. Patients undergoing PCI for acute myocardial infarction were excluded. Mortality was derived using the Social Security Death Index. Short-term (≤30-day) mortality rates in the LMCA PCI group (n = 468, 1.9%) were similar to the death rate in the multivessel PCI group (n = 1,973, 1.3%, p = 0.3). There was no significant difference in adjusted mortality between the 2 study groups. Stratifying LMCA PCI by the number of concomitant vessel territories treated, there was no significant difference in mortality in any LMCA PCI category (LMCA only, LMCA + 1-vessel PCI, LMCA + multivessel PCI) compared to multivessel PCI. In conclusion, there was comparable short-term and long-term mortality in the LMCA PCI and multivessel PCI groups. LMCA stenting did not appear to incur incremental risk compared to multivessel PCI.

Enhanced prediction of mortality after percutaneous coronary intervention by consideration of general and neurological indicators.

OBJECTIVES: This study sought to improve methodology for predicting post-percutaneous coronary intervention (PCI) mortality. BACKGROUND: Recently, an increased proportion of post-PCI deaths caused by noncardiac causes has been suggested, often in rapidly triaged patients resuscitated from sudden cardiac death or presenting with cardiogenic shock. Older risk adjustment algorithms may not adequately reflect these issues. METHODS: Consecutive patients undergoing PCI from 2000 to 2009 were randomly divided into training (n = 8,966) and validation (n = 8,891) cohorts. The 2010 ACC-NCDR (American College of Cardiology-National Cardiovascular Data Registry) mortality algorithm was applied to the training cohort and its highest risk decile, separately. Variables describing general and neurological status at admission were then tested for their additional predictive capability and new algorithms developed. These were tested in the validation cohort, using receiver-operator characteristic curve, Hosmer-Lemeshow, and reclassification measures as principal outcome measures. RESULTS: In-hospital mortality was 1.0%, of which 52.2% had noncardiac causes or major contributions. Baseline model C-statistics for the total and upper decile training cohorts were 0.904 and 0.830. The Aldrete score (addressing consciousness, respiration, skin color, muscle function, and circulation) and neurology scores added incremental information, resulting in improved validation cohort C-statistics (entire group: 0.883 to 0.914, p < 0.001; high-risk decile: 0.829 to 0.874, p < 0.001). Reclassification of the ACC-NCDR <90th and ≥90th risk percentiles by the new score yielded improved mortality prediction (p < 0.001 and p = 0.033, respectively). CONCLUSIONS: Half of in-hospital deaths in this series were of noncardiac causation. Prediction of in-hospital mortality after PCI can be considerably improved over conventional models by the inclusion of variables describing general and neurological status.

Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients.

BACKGROUND: Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD). A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. RESULTS: Microarray analysis of RNA samples from a 195 patient Duke CATHGEN registry case:control cohort yielded 2,438 genes with significant CAD association (p < 0.05), and identified the clinical/demographic factors with the largest effects on gene expression as age, sex, and diabetic status. RT-PCR analysis of 88 CAD classifier genes confirmed that diabetic status was the largest clinical factor affecting CAD associated gene expression changes. A second microarray cohort analysis limited to non-diabetics from the multi-center PREDICT study (198 patients; 99 case: control pairs matched for age and sex) evaluated gene expression, clinical, and cell population predictors of CAD and yielded 5,935 CAD genes (p < 0.05) with an intersection of 655 genes with the CATHGEN results. Biological pathway (gene ontology and literature) and statistical analyses (hierarchical clustering and logistic regression) were used in combination to select 113 genes for RT-PCR analysis including CAD classifiers, cell-type specific markers, and normalization genes.RT-PCR analysis of these 113 genes in a PREDICT cohort of 640 non-diabetic subject samples was used for algorithm development. Gene expression correlations identified clusters of CAD classifier genes which were reduced to meta-genes using LASSO. The final classifier for assessment of obstructive CAD was derived by Ridge Regression and contained sex-specific age functions and 6 meta-gene terms, comprising 23 genes. This algorithm showed a cross-validated estimated AUC = 0.77 (95% CI 0.73-0.81) in ROC analysis. CONCLUSIONS: We have developed a whole blood classifier based on gene expression, age and sex for the assessment of obstructive CAD in non-diabetic patients from a combination of microarray and RT-PCR data derived from studies of patients clinically indicated for invasive angiography. CLINICAL TRIAL REGISTRATION INFORMATION: PREDICT, Personalized Risk Evaluation and Diagnosis in the Coronary Tree, http://www.clinicaltrials.gov, NCT00500617.

The clinical impact of routine angiographic follow-up in randomized trials of drug-eluting stents: a critical assessment of "oculostenotic" reintervention in patients with intermediate lesions.

OBJECTIVES: The aim of this study was to study the long-term clinical effects of routine angiographic follow-up and related reintervention after drug-eluting stenting. BACKGROUND: Prior stent trials have shown that protocol-mandated angiographic follow-up increases repeat interventions compared with clinical follow-up alone. The long-term clinical impact of this practice is unknown. METHODS: Long-term outcomes of patients assigned to routine angiographic follow-up in 3 large-scale TAXUS (Boston Scientific, Natick, Massachusetts) trials were compared with patients assigned to clinical follow-up alone, in a propensity score-adjusted patient-level meta-analysis. Outcomes were also compared in patients with treated versus untreated nonischemic intermediate lesions (quantitative angiographic stenosis between >or=40% and <70%) detected at angiographic follow-up. RESULTS: Target lesion revascularization (TLR) rates at 5 years were significantly higher in the angiographic compared with clinical follow-up cohort (18.3% vs. 11.1%, p < 0.001). This was due to more frequent treatment of intermediate lesions, but there was no associated reduction in rates of cardiac death or myocardial infarction (8.9% vs. 8.8%, p = 0.93). Of patients with nonischemic intermediate lesions, 17% who were not revascularized at the time of angiographic follow-up had a subsequent TLR, whereas 7% of patients who had TLR at this follow-up angiogram required additional revascularization during long-term follow-up. CONCLUSIONS: A strategy of routine angiographic follow-up increases oculostenotic revascularization of nonischemic intermediate lesions without affecting subsequent rates of cardiac death or myocardial infarction, and TLR was not required in 83% of those lesions. A conservative approach, in which repeat angiography is limited to patients with recurrent ischemia or progressive symptoms, minimizes repeat revascularization of nonischemic intermediate lesions and optimizes long-term event-free survival after drug-eluting stent implantation.

Cost effectiveness of paclitaxel-eluting stents for patients undergoing percutaneous coronary revascularization: results from the TAXUS-IV Trial.

OBJECTIVES: This study sought to compare aggregate medical care costs for patients undergoing percutaneous coronary intervention with paclitaxel-eluting stents (PES) and bare-metal stents (BMS) and to formally evaluate the incremental cost effectiveness of PES for patients undergoing single-vessel percutaneous coronary intervention. BACKGROUND: Although the cost effectiveness of SES has been studied in both clinical trials and decision-analytic models, few data exist on the cost effectiveness of alternative drug-eluting stent (DES) designs. In addition, no clinical trials have specifically examined the cost effectiveness of DES among patients managed without mandatory angiographic follow-up. METHODS: We performed a prospective economic evaluation among 1,314 patients undergoing percutaneous coronary revascularization randomized to either PES (N = 662) or BMS (N = 652) in the TAXUS-IV trial. Clinical outcomes, resource use, and costs (from a societal perspective) were assessed prospectively for all patients over a 1-year follow-up period. Cost effectiveness was defined as the incremental cost per target vessel revascularization (TVR) event avoided and was analyzed separately among cohorts assigned to mandatory angiographic follow-up (n = 732) or clinical follow-up alone (n = 582). RESULTS: The PES reduced TVR by 12.2 events per 100 patients treated, resulting in a 1-year cost difference of 572 dollars per patient with incremental cost-effectiveness ratios of 4,678 dollars per TVR avoided and 47,798 dollars/quality-adjusted life year (QALY) gained. Among patients assigned to clinical follow-up alone, the net 1-year cost difference was 97 dollars per patient with cost-effectiveness ratios of 760 dollars per TVR event avoided and $5,105/QALY gained. CONCLUSIONS: In the TAXUS-IV trial, treatment with PES led to substantial reductions in the need for repeat revascularization while increasing 1-year costs only modestly. The cost-effectiveness ratio for PES in the study population compares reasonably with that for other treatments that reduce coronary restenosis, including alternative drug-eluting stent platforms.