Coronary Artery Disease: Mark DB

Becker RC, Meade TW, Berger PB, Ezekowitz M, O'Connor CM, Vorchheimer DA, Guyatt GH, Mark DB, Harrington RA, Anonymous00140. · Duke Cardiovascular Thrombosis Center, Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA. · Chest. · Pubmed #18574278 links to  free full text

Abstract: The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).

Newman MF, Blumenthal JA, Mark DB. · No affiliation provided · Circulation. · Pubmed #15569848 links to  free full text

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Newman MF, Mathew JP, Grocott HP, Mackensen GB, Monk T, Welsh-Bohmer KA, Blumenthal JA, Laskowitz DT, Mark DB. · Department of Anesthesiology, Duke University Medical Center, Durham, NC 277110, USA. · Lancet. · Pubmed #16920475 No free full text.

Abstract: Millions of individuals with coronary artery or valvular heart disease have been given a new chance at life by heart surgery, but the potential for neurological injury is an Achilles heel. Technological advancements and innovations in surgical and anaesthetic technique have allowed us to offer surgical treatment to patients at the extremes of age and infirmity-the group at greatest risk for neurological injury. Neurocognitive dysfunction is a complication of cardiac surgery that can restrict the improved quality of life that patients usually experience after heart surgery. With a broader understanding of the frequency and effects of neurological injury from cardiac surgery and its implications for patients in both the short term and the long term, we should be able to give personalised treatments and thus preserve both their quantity and quality of life. We describe these issues and the controversies that merit continued investigation.

Mark DB, Shaw LJ, Lauer MS, O'Malley PG, Heidenreich P. · Duke Clinical Research Institute, Duke University, PO Box 17969, Durham, NC 27115, USA. · J Am Coll Cardiol. · Pubmed #12798557 No free full text.

This publication has no abstract.

Hlatky MA, Boothroyd DB, Melsop KA, Brooks MM, Mark DB, Pitt B, Reeder GS, Rogers WJ, Ryan TJ, Whitlow PL, Wiens RD. · Stanford University School of Medicine, HRP Redwood Building, Room 150, Stanford, CA 94305-5405, USA. · Circulation. · Pubmed #15451795 links to  free full text

Abstract: BACKGROUND: Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. METHODS AND RESULTS: Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to 12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was 123,000 dollars versus 120,750 dollars for PTCA, yielding a cost-effectiveness ratio of 14,300 dollars/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. CONCLUSIONS: Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.

Kaul P, Armstrong PW, Fu Y, Knight JD, Clapp-Channing NE, Sutherland W, Granger CB, Mark DB, Anonymous00240. · University of Alberta, Edmonton. · Can J Cardiol. · Pubmed #15229756 links to  free full text

Abstract: BACKGROUND: Comparing American and Canadian practice patterns and outcomes offers a natural experiment to examine the relative benefits of aggressive versus conservative management of coronary artery disease. In a prospective substudy of the Global Use of Strategies to Open Occluded Coronary Arteries IIb (GUSTO-IIb) trial, differences in the management of non-ST elevation acute coronary syndrome, and the associated impact on quality of life (QOL) outcomes, were examined in the two countries. METHODS AND RESULTS: The patient population, selected randomly from the parent trial population, comprised 390 Canadian and 1122 American patients for whom both baseline and one-year data were available. Validated instruments were used to assess QOL, including the Duke Activity Status Index (DASI) and scales from the SF-36 questionnaire. At baseline, American patients had significantly higher cardiac catheterization rates (83% versus 45%), percutaneous coronary intervention rates (39% versus 24%) and coronary bypass surgery rates (19% versus 12%) than did Canadian patients, respectively. However, at one year, Canadian coronary bypass surgery rates were at par with those in the United States (24% versus 26%, respectively). At baseline, the mean DASI score was 24.6 among Canadian patients and 23.4 among American patients (P=0.14). At one year, neither cohort reported any significant change in functional scores and there was no intercountry difference in DASI scores, even after accounting for baseline risk. Canadian patients had significantly worse mental health scores than American patients at baseline (mean score 71.6 versus 75.4, respectively; P=0.02), but by one year, Canadian patients had better scores (mean score 80.1 versus 76.2, respectively; P=0.01). After adjusting for baseline characteristics, Canadian patients continued to report better mental health status scores than did American patients (4 points higher, P<0.01). When asked to rate their health state on a scale from 0 to 100, both cohorts reported similar values at baseline. However, after adjusting for baseline characteristics, American patients' perception of their health state was better than that reported by Canadians (3 points higher, P<0.01). CONCLUSION: Despite higher rates of invasive procedures in the American cohort, one-year QOL outcomes in the cohort were similar to those in the more conservatively managed Canadian cohort. These results suggest that routine cardiac catheterization and increased procedure use may be associated with diminishing marginal returns with respect to improving QOL outcomes among patients with non-ST elevation acute coronary syndromes.

Brummett BH, Babyak MA, Mark DB, Clapp-Channing NE, Siegler IC, Barefoot JC. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. · Ann Behav Med. · Pubmed #14979860 No free full text.

Abstract: BACKGROUND: Psychological stress is known to have a negative effect on the health and well-being of coronary artery disease (CAD) patients. Although the study of stress CAD samples has received considerable attention, few studies have examined the effects of gender and age, had multiple follow-ups over an extended period, and had extensive baseline assessment batteries. PURPOSE: In this study, demographic, clinical, social, and personality variables were evaluated as predictors of nine repeated assessments of stress over a 2-year period in 322 CAD patients (33.2% female). METHODS: At baseline, perceived social support, coping style, and social conflict were associated with stress ratings. Mixed models were used to evaluate predictors of reported stress during the subsequent 2 years. RESULTS: The results showed that higher stress was present in patients who were female and young. Follow-up stress was also found in patients with moderate income, congestive heart failure, high social conflict, low social support, and negative coping style. CONCLUSIONS: These findings may help clinicians identify patients who are likely to experience higher levels of stress over a prolonged period following a diagnosis of CAD and may also suggest which patients may benefit most from stress reduction interventions.

Hassan SA, Hlatky MA, Boothroyd DB, Winston C, Mark DB, Brooks MM, Eagle KA. · Henry Ford Hospital, Detroit, Michigan, USA. · Am J Med. · Pubmed #11239843 No free full text.

Abstract: PURPOSE: Previous studies have shown that coronary artery bypass surgery reduces the risk of cardiac complications after noncardiac surgery. Whether coronary angioplasty provides equivalent protection is not known. SUBJECTS AND METHODS: Patients were randomly assigned to undergo cardiac artery bypass surgery or angioplasty as part of the Bypass Angioplasty Revascularization Investigation trial. All subsequent noncardiac surgeries during a mean (+/- SD) follow-up of 7.7 years were recorded among participants in the ancillary Study of Economics and Quality of Life. Rates of mortality and nonfatal myocardial infarction, length of stay, and hospital costs were compared by the original randomized assignment. RESULTS: A total of 501 patients had noncardiac surgery at a median of 29 months after their most recent coronary revascularization procedure. Mortality and nonfatal myocardial infarction within 30 days of the first noncardiac surgery occurred in 4 of the 250 of the surgery-assigned patients and in 4 of the 251 of the angioplasty-assigned patients (P = 1.0). There were no significant differences in the mean length of hospital stay (6.3 +/- 6.7 versus 6.2 +/- 6.8 days; P = 0.47) or hospital cost ($8,920 +/- $11,511 versus $7,785 +/- $7,643; P = 0.33) between the surgery and angioplasty groups. Similar results were obtained when subsequent noncardiac procedures were included in the analysis. CONCLUSION: Rates of myocardial infarction and death after noncardiac surgery are similarly low after contemporary bypass surgery or angioplasty in patients with multivessel coronary artery disease.

Pepine CJ, Mark DB, Bourassa MG, Chaitman BR, Davies RF, Knatterud GL, Forman S, Pratt CM, Sopko G, Conti CR. · University of Florida College of Medicine, Division of Cardiovascular Medicine, Gainesville, USA. · Am J Cardiol. · Pubmed #10614796 No free full text.

Abstract: Costs for management of myocardial ischemia are enormous, yet comparison cost and outcome data for various ischemia treatment strategies from randomized trials are lacking and will require cost and resource utilization data from a large prospective trial. The Asymptomatic Cardiac Ischemia Pilot provided feasibility data for planning such a trial and an opportunity to estimate the long-term costs of different treatment strategies. Economic implications for ischemia management were compared in 558 patients with stable coronary artery disease and myocardial ischemia during both stress testing and daily life. Participants were randomized to 3 different initial treatment strategies and followed for 2 years. Based on cost trends over follow-up, costs for subsequent care were estimated. As expected, due to initial procedural costs, at 3 months, estimated costs for revascularization were approximately 10 times greater than costs for a medical care strategy. Extrapolated costs for anticipated resource consumption for care beyond 2 years, however, were approximately 2 times greater for an initial medical care strategy than for initial revascularization. This was due to increased need for drugs and hospitalizations for both late revascularizations and other ischemia-related events. Estimated costs for anticipated care in the medical strategies reached the anticipated cost of the revascularization strategy within 10 years. Because this cost-equal time period is well within the median life expectancy for such a patient population, these findings could have important public health implications and require testing in a full-scale prognosis trial. We anticipate that over the patients' life expectancy, early revascularization is likely to become either cost-neutral or cost-effective.

Hlatky MA, Boothroyd DB, Brooks MM, Winston C, Rosen A, Rogers WJ, Reeder GS, Smith HC, Ryan TJ, Pitt B, Whitlow PL, Wiens RD, Mark DB. · Department of Health Research and Policy, Stanford University School of Medicine, HRP Redwood Bldg, Room 150, Stanford, 94305-5405, USA. · Am Heart J. · Pubmed #10426855 No free full text.

Abstract: BACKGROUND: Medical costs vary substantially among patients. Understanding the baseline factors that predict subsequent cost may allow better selection of therapy for individual patients. Understanding the postprocedure events that increase cost should help to improve efficiency and effectiveness of coronary revascularization. METHODS: Data on 4-year costs were collected from patients randomly assigned to coronary angioplasty or bypass surgery as part of the BARI (Bypass Angioplasty Revascularization Investigation) trial. Regression models first examined factors known at the time of randomization that prospectively predicted initial procedure cost and long-term cost. Subsequent models tested the value of postrandomization events as explanatory variables for cost. RESULTS: The independent baseline predictors of higher initial percutaneous transluminal coronary angioplasty cost included 3-vessel disease (+12%) and acute presentations (+22%), whereas the independent predictors of higher initial coronary artery bypass grafting cost included the number of comorbid conditions (+5% per condition) and female sex (+7%). The independent baseline predictors of 4-year cost included heart failure (+26%), diabetes (+22%), comorbidity (+10%), and angioplasty assignment in patients with 2-vessel disease (-15%). Postrandomization models showed higher initial and long-term costs were strongly correlated with the number of repeat revascularization procedures (+30% to +128%) and the occurrence of clinical complications (+8% to +131%). CONCLUSIONS: Two-vessel disease identifies patients likely to have lower costs after angioplasty, whereas heart failure, comorbid conditions, and diabetes identify patients likely to accrue higher costs after either angioplasty or bypass surgery. Long-term costs can be potentially reduced by interventions that decrease procedural complications or reduce the need for repeat revascularization.

Brummett BH, Morey MC, Boyle SH, Mark DB. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 2969, Durham, NC 27710, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #19515993 No free full text.

Abstract: We examined associations between positive emotion (PE) and functional status (Duke Activity Status Inventory) in 948 coronary artery disease (CAD) patients (35.1% women; age M = 70.1 years, SD = 6.3). Emotion and function measures were gathered during hospitalization and annually for 3 years. We used random coefficient models to examine PE during hospitalization and follow-up, as a predictor of change in function. Analyses adjusted for baseline functional status, negative emotion, social support, marital status, and disease severity. Sex was examined as a moderator of effects. PE assessed during hospitalization was a significant predictor of change in function such that lower levels of PE were associated with accelerated decline in function. Lower levels of PE during follow-up were also related to increasing decline in function but only in men. Thus, our findings indicate that PE is associated with less decline in functional status following hospitalization for CAD.

Kruk M, Kadziela J, Reynolds HR, Forman SA, Sadowski Z, Barton BA, Mark DB, Maggioni AP, Leor J, Webb JG, Kapeliovich M, Marin-Neto JA, White HD, Lamas GA, Hochman JS. · Institute of Cardiology, Warsaw, Poland. · JACC Cardiovasc Interv. · Pubmed #19194534 No free full text.

Abstract: OBJECTIVES: This study sought to determine predictors of outcome and examine the influence of baseline risk on therapeutic impact of late mechanical opening of a persistently occluded infarct related artery after myocardial infarction in stable patients. BACKGROUND: Previous studies in patients with acute coronary syndromes suggest that the impact of infarct-related artery recanalization on clinical outcome is greatest in patients at highest risk. METHODS: Of 2,201 patients (age 58.6 +/- 11.0 years) with infarct-related artery occlusion on days 3 to 28 after myocardial infarction in the OAT (Occluded Artery Trial) study, 1,101 were assigned to percutaneous coronary intervention (PCI) and 1,100 to medical therapy alone and followed for a mean of 3.2 years. The primary end point was a composite of death, reinfarction, or New York Heart Association functional class IV heart failure. Interaction of treatment effect with tertiles of predicted survival were examined using the Cox survival model. RESULTS: The 5-year rate for the primary end point was 18.9% versus 16.1% for patients assigned to PCI and medical treatment alone, respectively (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.92 to 1.43, p 0.23). Lack of benefit of PCI was consistent across the risk spectrum for both the primary end point and total mortality, including for the highest tertile (33.9% PCI vs. 27.3% medical treatment alone, HR: 1.27, 99% CI: 0.87 to 1.85 primary end point and 23.5% PCI vs. 21.7% medical treatment alone, HR: 1.16, 99% CI: 0.73 to 1.85 mortality). The independent predictors of the composite outcome were history of heart failure (HR: 2.06, p < 0.001), peripheral vascular disease (HR: 1.93, p 0.001), diabetes (HR: 1.49, p 0.002), rales (HR: 1.88, p < 0.001), decreasing ejection fraction (HR: 1.48 per 10%, p < 0.001), decreasing days from myocardial infarction to randomization (HR: 1.04 per day, p < 0.001), and decreasing glomerular filtration rate (HR: 1.11 per 10 ml/min/1.73 m(2), p < 0.001). CONCLUSIONS: In the OAT study, there was no variation in the effect of PCI on clinical outcomes at different levels of patient risk, including the subset with very high event rates. (Occluded Artery Trial [OAT]; NCT00004562)

Kim JH, Newby LK, Clare RM, Shaw LK, Lodge AJ, Smith PK, Jolicoeur EM, Rao SV, Becker RC, Mark DB, Granger CB. · Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA. · Am Heart J. · Pubmed #19061702 No free full text.

Abstract: BACKGROUND: Short-term use of clopidogrel plus aspirin among patients with acute coronary syndrome reduces ischemic events, but concerns about coronary artery bypass graft (CABG) surgery-related bleeding limit its early use. METHODS: Using data from 4,794 consecutive CABG procedures in the Duke Databank for Cardiovascular Disease (January 1999 to December 2003), we developed multivariable models for associations with CABG-related bleeding defined as reoperation for bleeding, red cell transfusion, and a composite of reoperation/transfusion/hematocrit drop>or=15%. We examined clopidogrel use<or=5 days versus no clopidogrel<or=5 days before CABG in each model. Models were adjusted for propensity for clopidogrel use<or=5 days. RESULTS: Of 4,794 CABG patients, 332 (6.9%) received clopidogrel<or=5 days before CABG, 127 (2.6%) had reoperation for bleeding, 3,277 (68.4%) received red cell transfusion, and 4,387 (91.5%) had the composite outcome. After adjustment, clopidogrel use<or=5 days was not significantly associated with reoperation (odds ratio [OR] 1.24, 95% CI 0.63-2.41) or the composite end point (OR 1.23, 95% CI 0.72-2.10). Clopidogrel<or=5 days was modestly associated with red cell transfusion (OR 1.40, 95% CI 1.04-1.89) but more weakly than other factors, including which surgeon performed the procedure. CONCLUSION: Clopidogrel administration<or=5 days before CABG was not significantly associated with reoperation for bleeding or a bleeding composite, and only weakly with red cell transfusion after surgery. The impact of withholding clopidogrel acutely in those for whom clopidogrel has proven benefits and the impact of delaying CABG to prevent bleeding among patients treated with clopidogrel should be viewed in the context of other stronger determinants of bleeding.

Mark DB, Knight JD, Cowper PA, Davidson-Ray L, Anstrom KJ. · Outcomes Research Group, Duke Clinical Research Institute, Durham, NC 27715, USA. · Am Heart J. · Pubmed #18926150 No free full text.

Abstract: BACKGROUND: In 10,001 patients with stable coronary artery disease (CAD) enrolled in the Treating to New Targets (TNT) trial, 80 mg/d of atorvastatin (high-dose regimen) reduced the composite primary end point of death from CAD, nonfatal myocardial infarction, resuscitation from cardiac arrest, or stroke by 22% relative to 10 mg/d (low-dose regimen). METHODS: We performed an economic analysis of this trial from the US perspective using hospital bills and Medicare physician fees to estimate costs for cardiovascular hospitalizations in all US patients (n = 5,308). Atorvastatin costs were assigned using a discounted average wholesale price. Cost-effectiveness was calculated as the within-trial incremental cost required to prevent one primary end point event with high-dose atorvastatin. RESULTS: During a mean 4.9-year follow-up, the high-dose arm had fewer potential end point cardiovascular hospitalizations (35% vs 41%, P < .001) and revascularization procedures (16% vs 22%, P < .001). The high-dose regimen was $1 per day more expensive. At the end of 5 years, cumulative incremental cost for the high-dose arm was $252 (95% CI-$722 to +$1,276). With an absolute reduction in the primary end point of 2.8 per 100 treated with the high-dose regimen, the cost to prevent one additional primary end point event was $8,964. CONCLUSION: High-dose atorvastatin treatment of 5 years had only a small net incremental cost because of reduced complications and procedures. The cost to prevent one additional primary end point event with high-dose therapy was similar to that for drug-eluting stents versus bare metal stents in stable CAD and for early invasive versus early conservative therapy in acute coronary syndromes.

Anstrom KJ, Kong DF, Shaw LK, Califf RM, Kramer JM, Peterson ED, Rao SV, Matchar DB, Mark DB, Harrington RA, Eisenstein EL. · Department of Biostatistics, Duke Clinical Research Institute, Durham, NC 27715, USA. · Arch Intern Med. · Pubmed #18695078 No free full text.

Abstract: BACKGROUND: Clinical trials of drug-eluting stents (DES) vs bare metal stents (BMS) report a reduced need for target lesion revascularization with no difference in death or myocardial infarction. However, these trials selectively enrolled patients with lower risk, single-vessel coronary artery disease (CAD) and limited the follow-up period to 1 year or less. Thus, it is not known how these short-term results apply to patients with higher risk, multivessel CAD seen in community practice settings. The objective of this study was to compare the long-term clinical outcomes of patients receiving DES vs BMS in a clinical practice setting. METHODS: Patients from the Duke Databank for Cardiovascular Disease undergoing their initial revascularization with DES or BMS from January 1, 2000, through July 31, 2005, were included in the study population. Propensity scores and inverse probability weighted estimators were used to adjust for treatment group imbalances. RESULTS: The study population included 1501 patients who received DES and 3165 who received BMS. After adjustment, DES reduced target vessel revascularization (TVR) rates at 6, 12, and 24 months compared with BMS (24-month rates: DES, 6.6%; BMS, 16.3%; difference, -9.7%; 95% confidence interval [CI], -11.7% to -7.7%; P < .001). The TVR benefit for DES increased among patients with multivessel CAD (1-vessel CAD: -8.3%; 95% CI, -10.9% to -5.8%; P < .001; 2-vessel CAD: -9.7%; 95% CI, -3.6% to -5.8%; P < .001; 3-vessel CAD: -16.2%; 95% CI, -25.2% to -7.2%; P < .001). However, in the overall cohort there were no statistically significant differences in the composite of death or myocardial infarction. CONCLUSIONS: Patients receiving DES vs BMS in a clinical practice setting have lower TVR rates, albeit with less absolute benefit than those observed in clinical trials. Patients with multivessel vs single-vessel disease experience a greater reduction in TVR.

Velazquez EJ, Lee KL, O'Connor CM, Oh JK, Bonow RO, Pohost GM, Feldman AM, Mark DB, Panza JA, Sopko G, Rouleau JL, Jones RH, Anonymous00315. · Division of Cardiovascular Medicine, Department of Medicine, Duke University Medical Center, Durham, NC; Duke Clinical Research Institute, Durham, NC, USA. · J Thorac Cardiovasc Surg. · Pubmed #18023680 No free full text.

Abstract: OBJECTIVES: The rationale and design of the Surgical Treatment for Ischemic Heart Failure trial is described. Before the Surgical Treatment for Ischemic Heart Failure trial, less than 1000 patients with ischemic cardiomyopathy had been studied in randomized comparisons of medical therapy versus coronary artery bypass grafting. Trial data reflect how these therapies were delivered more than 20 years ago and do not indicate the relative benefits of medical therapy versus coronary artery bypass grafting in contemporary practice. METHODS: Randomization of consenting patients with heart failure, left ventricular ejection fraction of 0.35 or less, and coronary artery disease is based on whether patients are judged by attending physicians to be candidates only for coronary artery bypass grafting or can be treated with medical therapy without coronary artery bypass grafting. Patients eligible for surgical ventricular reconstruction because of significant anterior wall akinesis or dyskinesis but ineligible for medical therapy are randomly assigned to coronary artery bypass grafting with or without surgical ventricular reconstruction. Patients eligible for medical therapy are randomly assigned between medical therapy only and medical therapy with coronary artery bypass grafting. Patients eligible for all 3 are randomly assigned evenly to medical therapy only, medical therapy and coronary artery bypass grafting, or medical therapy and coronary artery bypass grafting and surgical ventricular reconstruction. Major substudies will examine quality of life, cost-effectiveness, changes in left ventricular volumes, effect of myocardial viability, selected biomarkers, and selected polymorphisms on treatment differences. RESULTS: Enrollment is now complete in both STICH hypotheses. Follow-up will continue until sufficient end points are available to address both hypotheses with at least 90% power. The primary outcome of hypothesis 2 is expected to be reported in 2009. The primary outcome of hypothesis 1 is expected to be reported in 2011. CONCLUSIONS: The Surgical Treatment for Ischemic Heart Failure trial is a National Heart, Lung, and Blood Institute-funded multicenter international randomized trial addressing 2 specific primary hypotheses: (1) coronary artery bypass grafting with intensive medical therapy improves long-term survival compared with survival with medical therapy alone, and (2) in patients with anterior left ventricular dysfunction, surgical ventricular reconstruction to a more normal left ventricular size plus coronary artery bypass grafting improves survival free of subsequent hospitalization for cardiac cause when compared with that with coronary artery bypass grafting alone.

Jonassaint CR, Boyle SH, Williams RB, Mark DB, Siegler IC, Barefoot JC. · Department of Psychiatry, Duke University, Durham, North Carolina, USA. · Psychosom Med. · Pubmed #17510289 links to  free full text

Abstract: OBJECTIVE: To examine the NEO Personality Inventory (NEO PI) Openness to Experience (O) domain and its facets as predictors of cardiac deaths and all-cause mortality. METHODS: The NEO PI was administered to a sample of 977 coronary catheterization patients with significant coronary artery disease. Over an average 15-year follow-up period, 266 cardiac deaths and 463 total deaths occurred. The relationships of O scores to mortality were examined with Cox proportional hazard models. Each model included age, left ventricular ejection fraction, severity of congestive heart failure, and number of diseased vessels as covariates. RESULTS: The O domain score was not associated with all-cause mortality and only approached significance for decreased cardiac deaths (p = .055). However, a higher score for Openness to Feelings was associated with a decreased risk of cardiac death (p < .01) and all-cause mortality (p < .01). High Openness to Actions was also associated with decreased cardiac mortality (p < .01) and all-cause mortality (p = .03) risk. Higher Openness to Aesthetics and Ideas were only associated with decreased cardiac death risk (both p values <.04). In contrast, Openness to Fantasy and Values were not associated with longevity. Previous evidence suggested that educational achievement may account for the effects of Openness to Experience on mortality; however, controlling for educational achievement did not change the results. CONCLUSION: These findings suggest that greater emotional awareness and high curiosity, as indicated by the NEO PI Feelings and Actions facets, are associated with increased patient longevity independently of other risk factors and educational achievement.

Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, Kramer JM, Harrington RA, Matchar DB, Kandzari DE, Peterson ED, Schulman KA, Califf RM. · Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. · JAMA. · Pubmed #17148711 links to  free full text

Abstract: CONTEXT: Recent studies of drug-eluting intracoronary stents suggest that current antiplatelet regimens may not be sufficient to prevent late stent thrombosis. OBJECTIVE: To assess the association between clopidogrel use and long-term clinical outcomes of patients receiving drug-eluting stents (DES) and bare-metal stents (BMS) for treatment of coronary artery disease. DESIGN, SETTING, AND PATIENTS: An observational study examining consecutive patients receiving intracoronary stents at Duke Heart Center, a tertiary care medical center in Durham, NC, between January 1, 2000, and July 31, 2005, with follow-up contact at 6, 12, and 24 months through September 7, 2006. Study population included 4666 patients undergoing initial percutaneous coronary intervention with BMS (n = 3165) or DES (n = 1501). Landmark analyses were performed among patients who were event-free (no death, myocardial infarction [MI], or revascularization) at 6- and 12-month follow-up. At these points, patients were divided into 4 groups based on stent type and self-reported clopidogrel use: DES with clopidogrel, DES without clopidogrel, BMS with clopidogrel, and BMS without clopidogrel. MAIN OUTCOME MEASURES: Death, nonfatal MI, and the composite of death or MI at 24-month follow-up. RESULTS: Among patients with DES who were event-free at 6 months (637 with and 579 without clopidogrel), clopidogrel use was a significant predictor of lower adjusted rates of death (2.0% with vs 5.3% without; difference, -3.3%; 95% CI, -6.3% to -0.3%; P = .03) and death or MI (3.1% vs 7.2%; difference, -4.1%; 95% CI, -7.6% to -0.6%; P = .02) at 24 months. However, among patients with BMS (417 with and 1976 without clopidogrel), there were no differences in death (3.7% vs 4.5%; difference, -0.7%; 95% CI, -2.9% to 1.4%; P = .50) and death or MI (5.5% vs 6.0%; difference, -0.5%; 95% CI, -3.2% to 2.2%; P = .70). Among patients with DES who were event-free at 12 months (252 with and 276 without clopidogrel), clopidogrel use continued to predict lower rates of death (0% vs 3.5%; difference, -3.5%; 95% CI, -5.9% to -1.1%; P = .004) and death or MI (0% vs 4.5%; difference, -4.5%; 95% CI, -7.1% to -1.9%; P<.001) at 24 months. However, among patients with BMS (346 with and 1644 without clopidogrel), there continued to be no differences in death (3.3% vs 2.7%; difference, 0.6%; 95% CI, -1.5% to 2.8%; P = .57) and death or MI (4.7% vs 3.6%; difference, 1.0%; 95% CI, -1.6% to 3.6%; P = .44). CONCLUSIONS: The extended use of clopidogrel in patients with DES may be associated with a reduced risk for death and death or MI. However, the appropriate duration for clopidogrel administration can only be determined within the context of a large-scale randomized clinical trial.

Liao L, Kong DF, Shaw LK, Sketch MH, Milano CA, Lee KL, Mark DB. · Duke Clinical Research Institute, USA. · J Am Coll Cardiol. · Pubmed #16256869 No free full text.

Abstract: OBJECTIVES: The purpose of this study was to determine the value of a new anatomic score for prognosis after diagnostic catheterization in patients with previous coronary artery bypass grafting (CABG). BACKGROUND: Previous CABG patients comprise a growing proportion of patients with coronary artery disease (CAD). Whereas prognostic scores are available to adjust for native CAD, there are no comparable scores for patients with previous CABG. METHODS: We studied 3,178 previous CABG patients (2,729 in a training set) who underwent cardiac catheterization. With a Cox model to develop relative weights in the training set, we created a graft index that adjusted native anatomy for territories with grafts free of significant (> or =75%) stenoses. Scaling the regression coefficients by the maximum coefficient created an index ranging from 0 to 100, where 100 was three-vessel CAD with no patent grafts. RESULTS: The graft index was significantly associated with all-cause death (chi-square = 121.9, p < 0.001). In combined models, the index was more strongly associated with all-cause death than either number of diseased vessels (chi-square = 68.0 and 1.7, respectively) or the Duke CAD index (chi-square = 54.3 and 9.5, respectively). In models for death using an independent validation set, the index was also associated more strongly than either native disease descriptors. In a model including other clinical variables, the graft index remained significantly associated with all-cause death (chi-square = 40.1, p < 0.001). CONCLUSIONS: For previous CABG patients, the Duke graft index was significantly more associated with prognosis than native anatomy alone and quantifies the effect of patent grafts on survival. This tool has the potential to help determine prognosis and inform the referral of post-CABG patients to repeat revascularization procedures.

Boyle SH, Williams RB, Mark DB, Brummett BH, Siegler IC, Barefoot JC. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #15979435 No free full text.

Abstract: This study examined hostility as a predictor of survival in a sample of 1,328 patients who had documented coronary artery disease. After controlling for disease severity, there was a significant interaction between age and hostility. Hostility was significantly associated with poorer survival but only in younger (<61.2 years) patients.

Kaul P, Newby LK, Fu Y, Mark DB, Goodman SG, Wagner GS, Harrington RA, Granger CB, Van de Werf F, Ohman EM, Armstrong PW, Anonymous00139. · University of Alberta, Edmonton, Alberta, Canada. · Heart. · Pubmed #15958353 links to  free full text

Abstract: OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.

Brummett BH, Mark DB, Siegler IC, Williams RB, Babyak MA, Clapp-Channing NE, Barefoot JC. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 2969, Durham, NC 27710, USA. · Psychosom Med. · Pubmed #15673622 links to  free full text

Abstract: OBJECTIVE: Numerous studies have shown network assessments of social contact predict mortality in patients with coronary artery disease (CAD). Fewer studies have demonstrated an association between perceived social support and longevity in patient samples. It has been suggested that 1 of the mechanisms linking social support with elevated risk for mortality is the association between social support and other risk factors associated with decreased longevity such as smoking, failure to exercise, and depressive symptoms. The present study examined an assessment of perceived support as a predictor of all-cause and CAD mortality and examined the hypothesis that smoking, sedentary behavior, and depressive symptoms may mediate and/or moderate this association. METHODS: Ratings of social support and the risk factors of smoking, sedentary behavior, and depressive symptoms were examined as predictors of survival in 2711 patients with CAD, and associations between support and these risk factors were assessed. Smoking, sedentary behavior, and depressive symptoms were examined as mediators and/or moderators of the association between social support and mortality. RESULTS: Social support, smoking, sedentary behavior, and depressive symptoms were predictors of mortality (p's <.01). Results also indicated that sedentary behavior, but not smoking status or depressive symptoms, may substantially mediate the relationship between support and mortality. No evidence for moderation was found. CONCLUSIONS: The relation between social support and longevity may be partially accounted for by the association between support and sedentary behavior.

Boyle SH, Williams RB, Mark DB, Brummett BH, Siegler IC, Helms MJ, Barefoot JC. · Department of Psychiatry, Duke University Medical Center, Box 2969, Durham, NC, USA. · Psychosom Med. · Pubmed #15385683 links to  free full text

Abstract: OBJECTIVE: This article presents a reanalysis of an earlier study that reported a nonsignificant relation between the 50-item Cook-Medley Hostility Scale (CMHS) and survival in a sample of coronary patients. Since publication of those results, there have been significant developments in the measurement of hostility that suggest that an abbreviated scale may be a better predictor of health outcomes. This study examined the ability of the total CMHS and an abbreviated form of the CMHS (ACM) to predict survival in a sample of patients with documented coronary artery disease (CAD) with increased statistical power. METHODS: Nine hundred thirty-six patients (83% were male; mean age = 51.48) with CAD who were followed for an average of 14.9 years. The ACM consisted of the combination of the cynicism, hostile attribution, hostile affect, and aggressive responding subscales that were identified in an earlier study (Barefoot et al. [1989]) by a rational analysis of the item content. The relation between hostility and survival was examined with Cox proportional hazard models (hazard ratios [HRs] based on a two standard deviation difference). RESULTS: Controlling for disease severity, the ACM was a significant predictor for both CHD mortality (HR = 1.33, p <.009) and total mortality (HR = 1.28, p <.02). The total CMHS was only a marginally significant predictor of either outcome (p values < 0.06).CONCLUSION: The results of this study suggest that hostility is associated with poorer survival in CAD patients, and it may be possible to refine measures of hostility in order to improve prediction of health outcomes.

Sachdev M, Sun JL, Tsiatis AA, Nelson CL, Mark DB, Jollis JG. · Duke Clinical Research Institute, Duke University, Durham, North Carolina 27705, USA. · J Am Coll Cardiol. · Pubmed #14975466 No free full text.

Abstract: OBJECTIVES: To identify the prevalent and prognostically important coexisting illnesses among single coronary artery disease (CAD) patients. BACKGROUND: As the population ages, physicians are increasingly required to make decisions concerning patients with multiple co-existing illnesses (comorbidity). Many trials of CAD therapy have excluded patients with significant comorbidity, such that there are limited data to guide the management of those patients. METHODS: To consider the long-term prognostic importance of comorbid illness, we examined a cohort of 1471 patients with CAD who underwent cardiac catheterization between 1985 and 1989 and were followed up through 2000 in the Duke Databank for Cardiovascular Diseases. Weights were assigned to individual diseases according to their prognostic significance in Cox proportional hazards models, thus creating a new CAD-specific index. The new index was compared with the widely used Charlson index, according to prevalence of conditions, individual and overall associations with survival, and agreement. RESULTS: The Charlson index and the CAD-specific index were highly associated with long-term survival and almost equivalent to left ventricular ejection fraction. When considering the components of the Charlson index, diabetes, renal insufficiency, chronic obstructive pulmonary disease, and peripheral vascular disease had greater prognostic significance among CAD patients, whereas peptic ulcer disease, connective tissue disease, and lymphoma were less significant. Hemiplegia, leukemia, lymphoma, severe liver disease, and acquired immunodeficiency syndrome were rarely identified among patients undergoing coronary angiography. CONCLUSIONS: Comorbid disease is strongly associated with long-term survival in patients with CAD. These data suggest co-existing illnesses should be measured and considered in clinical trials, disease registries, quality comparisons, and counseling of individual patients.

Mark DB, Lauer MS. · Outcomes Research and Assessment Group, Duke Clinical Research Institute, Durham, NC 27715, USA. · Circulation. · Pubmed #14517147 links to  free full text

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