Troponin and Cardiac Events in Stable Ischemic Heart Disease and Diabetes.

BACKGROUND: Cardiac troponin concentrations are used to identify patients who would benefit from urgent revascularization for acute coronary syndromes. We hypothesized that they might be used in patients with stable ischemic heart disease to identify those at high risk for cardiovascular events who might also benefit from prompt coronary revascularization. METHODS: We measured the cardiac troponin T concentration at baseline with a high-sensitivity assay in 2285 patients who had both type 2 diabetes and stable ischemic heart disease and were enrolled in the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes trial. We tested for an association between the troponin T concentration and a composite end point of death from cardiovascular causes, myocardial infarction, or stroke; we then evaluated whether random assignment to prompt revascularization reduced the rate of the composite end point in patients with an abnormal troponin T concentration (≥14 ng per liter) as compared with those with a normal troponin T concentration (<14 ng per liter). RESULTS: Of the 2285 patients, 2277 (99.6%) had detectable (≥3 ng per liter) troponin T concentrations and 897 (39.3%) had abnormal troponin T concentrations at baseline. The 5-year rate of the composite end point was 27.1% among the patients who had had abnormal troponin T concentrations at baseline, as compared with 12.9% among those who had had normal baseline troponin T concentrations. In models that were adjusted for cardiovascular risk factors, severity of diabetes, electrocardiographic abnormalities, and coronary anatomy, the hazard ratio for the composite end point among patients with abnormal troponin T concentrations was 1.85 (95% confidence interval [CI], 1.48 to 2.32; P<0.001). Among patients with abnormal troponin T concentrations, random assignment to prompt revascularization, as compared with medical therapy alone, did not result in a significant reduction in the rate of the composite end point (hazard ratio, 0.96; 95% CI, 0.74 to 1.25). CONCLUSIONS: The cardiac troponin T concentration was an independent predictor of death from cardiovascular causes, myocardial infarction, or stroke in patients who had both type 2 diabetes and stable ischemic heart disease. An abnormal troponin T value of 14 ng per liter or higher did not identify a subgroup of patients who benefited from random assignment to prompt coronary revascularization. (Funded by the National Institutes of Health and Roche Diagnostics; BARI 2D ClinicalTrials.gov number, NCT00006305.).

Comparison of drug-eluting and bare metal stents in large coronary arteries: findings from the NHLBI dynamic registry.

OBJECTIVES: This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. BACKGROUND: Randomized trials have demonstrated that DES reduce the risk of target vessel revascularization (TVR) compared to BMS. This benefit is less pronounced as artery diameter increases. Whether DES are superior to BMS for larger coronary arteries in the setting of routine clinical practice is unknown. METHODS: We analyzed data from 869 patients undergoing de novo lesion PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI Dynamic Registry according to whether they were treated with DES or BMS. Patients were followed for 3 years for the occurrence of cardiovascular events. RESULTS: At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI 0.93-3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52-2.49, P = 0.75) and for mortality 0.89 (95%CI 0.49-1.62, P = 0.71). CONCLUSIONS: In our study of the unrestricted use of DES for patients with lesions in larger diameter coronary arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do not support the preferred use of DES over BMS for patients with lesions located in arteries >3.5 mm. It is unknown whether secondary generation DES can offer better outcome compared to BMS in large coronary vessels. Further study on this issue is warranted.

Direct stenting compared to balloon predilation in drug-eluting stents: one-year outcomes from the DEScover Registry.

OBJECTIVES: We sought to examine the determinants and outcomes of direct stenting (DS) compared to predilation with drug-eluting stents (DES). BACKGROUND: Limited data suggest that DS with DES is feasible and may reduce restenosis compared to predilation. Whether DS improves clinical outcomes in unselected patients treated with DES is unknown. METHODS: DEScover is a prospective, multicenter, observational study of percutaneous coronary intervention that enrolled patients in 2005. The analysis cohort included 4,210 patients who received a DES and had a single lesion treated with DS (n = 1,651) or predilation (n = 2,559) at the discretion of the operator. Multivariable analysis was performed for 1-year outcomes. RESULTS: DS was performed in 39.2% of patients. The direct stent patients were younger, less often male, and had a lesser extent of CAD. DS was performed less often in patients presenting with an acute myocardial infarction (MI) and more often in stable angina and elective procedures. Lesion characteristics differed with DS performed less often for calcified lesions, high-grade stenoses (>90%), and bifurcation lesions. Lesion postdilation was less common in direct stent patients (42.1% vs. 50.7%, P = 0.0001). Complete procedural success was similar (99.8% vs. predilation 99.7%, P = 0.46). At 1 year, there was no difference in the adjusted hazard ratios of death (0.67, 0.44-1.04, P = 0.08), MI (1.05, 0.66-1.67, P = 0.83), stent thrombosis (0.38, 0.13-1.14, P = 0.08), TLR (0.75, 0.48-1.17, P = 0.21), TVR (0.89, 0.64-1.23, P = 0.47), and major adverse coronary event (0.88, 0.71-1.09, P = 0.24). CONCLUSIONS: DS with DES is commonly performed in clinical practice and results in similar long-term outcomes as predilation.

A comparison of bare-metal and drug-eluting stents for off-label indications.

BACKGROUND: Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown. METHODS: We analyzed data from 6551 patients in the National Heart, Lung, and Blood Institute Dynamic Registry according to whether they were treated with drug-eluting stents or bare-metal stents and whether use was standard or off-label. Patients were followed for 1 year for the occurrence of cardiovascular events and death. Off-label use was defined as use in restenotic lesions, lesions in a bypass graft, left main coronary artery disease, or ostial, bifurcated, or totally occluded lesions, as well as use in patients with a reference-vessel diameter of less than 2.5 mm or greater than 3.75 mm or a lesion length of more than 30 mm. RESULTS: Off-label use occurred in 54.7% of all patients with bare-metal stents and 48.7% of patients with drug-eluting stents. As compared with patients with bare-metal stents, patients with drug-eluting stents had a higher prevalence of diabetes, hypertension, renal disease, previous percutaneous coronary intervention and coronary-artery bypass grafting, and multivessel coronary artery disease. One year after intervention, however, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug-eluting stents as compared with those with bare-metal stents, whereas the risk of repeat revascularization was significantly lower among patients with drug-eluting stents. CONCLUSIONS: Among patients with off-label indications, the use of drug-eluting stents was not associated with an increased risk of death or myocardial infarction but was associated with a lower rate of repeat revascularization at 1 year, as compared with bare-metal stents. These findings support the use of drug-eluting stents for off-label indications.

Temporal changes in the outcomes of patients with diabetes mellitus undergoing percutaneous coronary intervention in the National Heart, Lung, and Blood Institute dynamic registry.

BACKGROUND: Patients with diabetes mellitus (DM) are at higher risk for adverse outcomes following percutaneous coronary intervention (PCI). METHODS: To determine whether outcomes have improved over time, we analyzed data from 2,838 consecutive patients with medically treated DM, including 1,066 patients (37.6%) treated with insulin, in the National Heart, Lung, and Blood Institute Dynamic Registry undergoing PCI registered in waves 1 (1997-1998), 2 (1999), 3 (2001-2002), 4 (2004), and 5 (2006). We compared baseline demographics and 1-year outcomes in the overall cohort and in analyses stratified by recruitment wave and insulin use. RESULTS: Crude mortality rates by chronological wave were 9.5%, 12.5%, 8.9%, 11.6%, and 6.6% (P value(trend) = .33) among those treated with insulin and, respectively, 9.7%, 6.5%, 4.1%, 5.4%, and 4.7% (P value(trend) = .006) among patients treated with oral agents,. The adjusted hazard ratios of death, myocardial infarction (MI), and overall major adverse cardiovascular events (death, MI, revascularization) in insulin-treated patients with DM in waves 2 to 5 as compared with wave 1 were either higher or the same. In contrast, the similar adjusted hazard ratios for oral agent-treated patients with DM were either similar or lower. CONCLUSIONS: Significant improvements over time in adverse events by 1 year were detected in patients with DM treated with oral agents. In insulin-treated diabetic patients, despite lower rates of repeat revascularization over time, death and MI following PCI have not significantly improved. These findings underscore the need for continued efforts at optimizing outcomes among patients with DM undergoing PCI, especially those requiring insulin treatment.

Percutaneous coronary intervention of moderate to severe calcified coronary lesions: insights from the National Heart, Lung, and Blood Institute Dynamic Registry.

OBJECTIVES: To evaluate the efficacy and safety of drug eluting stents (DES) when compared with bare metal stents (BMS) in patients with moderate to severe calcified coronary lesions. BACKGROUND: Calcified coronary lesions present unique technical challenges during percutaneous coronary intervention (PCI) and it is not known if DES are as safe and as effective in the presence of calcium, as randomized trials typically exclude this common patient subset. METHODS: We evaluated patients with PCI of a single calcified lesion enrolled across five recruitment waves in the National Heart, Lung, and Blood Institute Dynamic Registry between 1997 and 2006. Patients were divided into two groups based on the stent type- BMS and DES. The primary efficacy outcome was the need for repeat revascularization at 1 year and the primary safety outcome was a composite of death and myocardial infarction at 1 year. RESULTS: Among the 1,537 patients included in the analysis, 884 (57%) underwent PCI with BMS and 653 (43%) with DES. DES use was associated with a significant reduction in the risk of repeat revascularization (10.0% vs. 15.3%; P = 0.003) with no significant higher risk of primary safety outcome (9.3% vs. 10.5%; P = 0.45) when compared to the BMS group. In a propensity score adjusted analysis, DES use was associated with a significantly lower risk in repeat revascularization (HR = 0.57; 95% CI 0.40-0.82; P = 0.002) and no significant difference in the risk of death and myocardial infarction (HR = 0.78; 95% CI 0.53-1.15; P = 0.20) compared to BMS group. CONCLUSION: In this large multicenter registry of patients with a moderate to severe calcified coronary lesion, use of DES compared to BMS was associated with significant reduction in the risk of repeat revascularization without any increase in death and myocardial infarction.

Death and Myocardial Infarction Following Initial Revascularization Versus Optimal Medical Therapy in Chronic Coronary Syndromes With Myocardial Ischemia: A Systematic Review and Meta-Analysis of Contemporary Randomized Controlled Trials.

Background In chronic coronary syndromes, myocardial ischemia is associated with a greater risk of death and nonfatal myocardial infarction (MI). We sought to compare the effect of initial revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) with OMT alone in patients with chronic coronary syndrome and myocardial ischemia on long-term death and nonfatal MI. Methods and Results Ovid Medline, Embase, Scopus, and Cochrane Library databases were searched for randomized controlled trials of PCI or CABG plus OMT versus OMT alone for patients with chronic coronary syndromes. Studies were screened and data were extracted independently by 2 authors. Random-effects models were used to generate pooled treatment effects. The search yielded 7 randomized controlled trials that randomized 10 797 patients. Median follow-up was 5 years. Death occurred in 640 of the 5413 patients (11.8%) randomized to revascularization and in 647 of the 5384 patients (12%) randomized to OMT (odds ratio [OR], 0.97; 95% CI, 0.86-1.09; P=0.60). Nonfatal MI was reported in 554 of 5413 patients (10.2%) in the revascularization arms compared with 627 of 5384 patients (11.6%) in the OMT arms (OR, 0.75; 95% CI, 0.57-0.99; P=0.04). In subgroup analysis, nonfatal MI was significantly reduced by CABG (OR, 0.35; 95% CI, 0.21-0.59; P<0.001) but was not reduced by PCI (OR, 0.92; 95% CI, 0.75-1.13; P=0.43) (P-interaction <0.001). Conclusions In patients with chronic coronary syndromes and myocardial ischemia, initial revascularization with PCI or CABG plus OMT did not reduce long-term mortality compared with OMT alone. CABG plus OMT reduced nonfatal MI compared with OMT alone, whereas PCI did not.

Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN.

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women's Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in-person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1-5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow-up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow-up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05-2.17], P=0.03; 1-5 days: HR [95% CI], 1.02 [0.75-1.39], P=0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33-2.35], P<0.0001, multivariable). Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female-specific CVD risk factor.

Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent.

BACKGROUND: The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP) near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD) related phenotypes. METHODS AND RESULTS: Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI) in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD) was significantly higher in older men (≥65 years) who were either homozygous or carriers of the obesity/lipid risk allele ("C") compared to non-carriers (odds ratio 3.4, p = 0.013) using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65) women (odds ratio 3.4, p = 0.013). The INSIG2 SNP was not associated with BMI, nor with other clinical variables. CONCLUSION: Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.

Influence of LDL-Cholesterol Lowering on Cardiovascular Outcomes in Patients With Diabetes Mellitus Undergoing Coronary Revascularization.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations. OBJECTIVES: This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM). METHODS: Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke). RESULTS: A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and <100 mg/dl and LDL-C <70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was <70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI. CONCLUSIONS: In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C <70 mg/dl.

BARI 2D: A Reanalysis Focusing on Cardiovascular Events.

OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus and stable coronary artery disease. PATIENTS AND METHODS: From January 1, 2001, to November 30, 2008, 2368 patients with type 2 diabetes mellitus and angiographically proven coronary artery disease were randomly assigned to insulin-sensitizing (IS) or insulin-providing (IP) therapy and simultaneously to coronary revascularization (REV) or no or delayed REV (intensive medical therapy [MED]), with all patients receiving intensive medical treatment. The outcome of this analysis was a composite of 8 CVD events. RESULTS: Four-year Kaplan-Meier rates for the composite CVD outcome were 35.8% (95% CI, 33.1%-38.5%) with IS therapy and 41.6% (95% CI, 38.7%-44.5%) with IP therapy (P=.004). Much of this difference was associated with lower in-trial levels of fibrinogen, C-reactive protein, and hemoglobin A1c with IS therapy. Four-year composite CVD rates were 32.7% (95% CI, 30.0%-35.4%) with REV and 44.7% (95% CI, 41.8%-47.6%) with MED (P<.001). A beneficial effect of IS vs IP therapy was present with REV (27.7%; 95% CI, 24.0%-31.4% vs 37.5%; 95% CI, 33.6%-41.4%; P<.001), but not with MED (43.6%; 95% CI, 39.5%-47.7% vs 45.7%; 95% CI, 41.6%-49.8%; P=.37) (homogeneity, P=.05). This interaction between IS therapy and REV was limited to participants preselected for coronary artery bypass grafting (CABG). The lowest composite CVD rates occurred in patients preselected for CABG and assigned to IS therapy and REV (17.3%; 95% CI, 11.8%-22.8%). CONCLUSION: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, the IS treatment strategy and the REV treatment strategy each reduces cardiovascular events. The combination of IS drugs and CABG results in the lowest risk of subsequent CVD events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006305.

Impact of Chronic Kidney Disease on Outcomes of Myocardial Revascularization in Patients With Diabetes.

BACKGROUND: The optimal coronary revascularization strategy in patients with stable ischemic heart disease (SIHD) who have type 2 diabetes (T2DM) and chronic kidney disease (CKD) remains unclear. OBJECTIVES: This patient-level pooled analysis sought to compare outcomes of 3 large, federally-funded randomized trials in SIHD patients with T2DM and CKD (COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation], BARI 2D [Bypass Angioplasty Revascularization Investigation 2 Diabetes], and FREEDOM [Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-vessel Disease]). METHODS: The primary endpoint was the composite of major adverse cardiovascular or cerebrovascular events (MACCE) including all-cause death, myocardial infarction (MI), or stroke adjusted for trial and randomization strategy. RESULTS: Of the 4,953 patients with available estimated glomerular filtration rate (eGFR) at baseline, 1,058 had CKD (21.4%). CKD patients were more likely to be older, be female, and have a history of heart failure. CKD subjects were more likely to experience a MACCE (adjusted hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28 to 1.71; p = 0.0001) during a median 4.5-year follow-up. Both mild (eGFR 45 to 60 ml/min/1.73 m2) and moderate to severe (eGFR <45 ml/min/1.73 m2) CKD predicted MACCE (adjusted HRs: 1.25 and 2.26, respectively). For patients without CKD, coronary artery bypass graft (CABG) surgery combined with optimal medical therapy (OMT) was associated with lower MACCE rates compared with percutaneous coronary intervention (PCI) + OMT (adjusted HR: 0.69; 95% CI: 0.55 to 0.86; p = 0.001). For the comparison of CABG + OMT versus PCI + OMT in the CKD group, there was only a statistically significant difference in subsequent revascularization rates (HR: 0.25; 95% CI: 0.15 to 0.41; p = 0.0001) but not in MACCE rates. CONCLUSIONS: Among SIHD patients with T2DM and no CKD, CABG + OMT significantly reduced MACCE compared with PCI + OMT. In subjects with CKD, there was a nonsignificant trend toward a better MACCE outcome with CABG and a significant reduction in subsequent revascularization.

A Randomized Clinical Trial of Wheeled Mobility for Pressure Injury Prevention and Better Function.

OBJECTIVES: To evaluate the effectiveness of wheelchair assessment and configuration on pressure injury incidence, mobility, and functioning in a wheelchair. DESIGN: Randomized controlled trial with participants individually randomized into intervention and control groups. SETTING: Nursing home. PARTICIPANTS: Nursing home residents aged 60 and older who used wheelchairs and were at risk for pressure injuries (N=258). INTERVENTION: Treatment and evaluation, individually configured wheelchair and skin protection cushion; control and evaluation, facility-provided wheelchair and skin protection cushion. MEASUREMENTS: Pressure injury incidence, Nursing Home Life Space Diameter score, Functioning Every Day in a Wheelchair-Capacity (FEW-C) score, and Wheelchair Skills Test (WST) score. RESULTS: No differences in pressure injuries (p=.77) were found. Pelvic rotation (odds ratio (OR)=0.15, 95% confidence interval (CI)=0.03-0.70, p=.02) and Day 14 WST skill score (OR=0.74, 95% CI=0.60-0.91, p=.004) were significant predictors of pressure injuries. Significant differences were observed between groups in change in FEW-C independence scores between before randomization and endpoint (p=.03) and before randomization and 14 days (p=.04). CONCLUSION: Participants with individually configured wheelchairs improved more in the safe and effective use of their wheelchairs than residents with facility-provided wheelchairs. The outcomes indicated that nursing home residents functioned safely at a higher level in their wheelchairs if their devices were individually configured using a comprehensive wheelchair and seating assessment process. There was no difference in the incidence of pressure injuries between the two groups. TRIAL REGISTRATION: NCT01275313.

Impact of treatment strategies on outcomes in patients with stable coronary artery disease and type 2 diabetes mellitus according to presenting angina severity: A pooled analysis of three federally-funded randomized trials.

BACKGROUND AND AIMS: The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed. METHODS: We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T2DM randomized to optimal medical therapy [OMT], percutaneous coronary intervention [PCI] + OMT, or coronary artery bypass grafting [CABG] + OMT. Endpoints were death/myocardial infarction (MI)/stroke, post-randomization revascularization (both over 5 years), and angina control at 1 year. RESULTS: Increasing severity of baseline angina was associated with higher rates of death/MI/stroke (p = 0.009) and increased need for post-randomization revascularization (p = 0.001); after multivariable adjustment, only association with post-randomization revascularization remained significant. Baseline angina severity did not influence the superiority of CABG + OMT to reduce the rate of death/MI/stroke and post-randomization revascularization compared to other strategies. CABG + OMT was superior for angina control at 1 year compared to both PCI + OMT and OMT alone but only in patients with ≥ Class II severity at baseline. Comparisons between PCI + OMT and OMT were neutral except that PCI + OMT was superior to OMT for reducing the rate of post-randomization revascularization irrespective of presenting angina severity. CONCLUSIONS: Presenting angina severity did not influence the superiority of CABG + OMT with respect to 5-year rates of death/MI/stroke and need for post-randomization revascularization. Presenting angina severity minimally influenced relative benefits for angina control at 1 year.

Hypoglycemia and Elevated Troponin in Patients With Diabetes and Coronary Artery Disease.

BACKGROUND: Diabetic medications can cause hypoglycemia, which may lead to myocardial damage. OBJECTIVES: This study sought to determine whether hypoglycemia is associated with higher levels of high-sensitivity cardiac troponin T (hsTnT). METHODS: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial randomized patients with type 2 diabetes mellitus and stable coronary artery disease, and closely followed them for hypoglycemia over the first year. Hypoglycemia was classified by maximum severity and frequency. hsTnT was measured at baseline and 1 year, and analyzed using multivariable regression. RESULTS: Of 1,984 patients, follow-up hypoglycemia was absent in 1,026 (52%) patients, mild in 875 (44%), and severe in 83 (4%), and occurred less than weekly in 561 (28%) and greater than or equal to weekly in 397 (20%). hsTnT levels were associated with hypoglycemia: a median of 11.4 ng/l (interquartile range [IQR]: 8.1 to 17.3 ng/l) for none, 12.5 ng/l (IQR: 8.3 to 19.3 ng/l) for mild, and 13.7 ng/l (IQR: 9.9 to 24.9 ng/l) for severe hypoglycemia (p = 0.0001); and 12.5 ng/l (IQR: 8.3 to 18.1 ng/l) for less than weekly and 13.0 ng/l (IQR: 8.8 to 21.1 ng/l) for greater than or equal to weekly hypoglycemia (p = 0.0013). Severe hypoglycemia was associated with 34% higher 1-year hsTnT levels (p < 0.0001) in unadjusted analysis, 17% higher (p = 0.006) after adjustment for baseline factors unrelated to diabetes, and 6% higher (p = 0.23) after further adjustment for the duration and severity of diabetes. Hypoglycemia greater than or equal to weekly was associated with 14% higher hsTnT (p = 0.0003) in unadjusted analysis, 12% higher (p = 0.0002) after adjustment for baseline factors unrelated to diabetes, and 4% higher (p = 0.16) after adjustment for diabetes related factors. CONCLUSIONS: Hypoglycemia was associated with elevated hsTnT levels, but this may be due to more severe diabetes in patients who developed hypoglycemia, rather than the direct result of hypoglycemia. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI2D]; NCT00006305).

Comparison of outcome in patients with ST-elevation versus non-ST-elevation acute myocardial infarction treated with percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) are increasingly being treated with percutaneous coronary intervention (PCI) and we sought to determine risk of adverse outcomes by type of MI. Patients enrolled in the National Heart, Lung, and Blood Institute Dynamic Registry from 1999 to 2004 who presented with an acute MI as an indication for PCI were studied. Baseline data and in-hospital and 1-year outcomes were compared based on ST-segment elevation (STEMI, n = 903; NSTEMI, n = 583) at presentation. Patients with STEMI were younger, had fewer co-morbidities, and had less extensive coronary artery disease than did patients with NSTEMI. Angiographic success and periprocedural complications were similar by MI type. In-hospital coronary artery bypass grafting, stroke, bleeding and recurrent MI were similar but mortality was higher in patients with STEMI (4.0% vs 1.4%, p = 0.004). Cardiogenic shock was associated with the greatest risk of in-hospital death (odds ratio 26.7, 95% confidence interval 11.4 to 62.3, p = 0.0001), but STEMI was also independently predictive of mortality. At 1 year, there was no influence of MI type on outcome. Age, cardiogenic shock, renal disease, peripheral vascular disease, and cancer were predictive of death and MI. Multivessel disease and a larger number of >50% lesions were associated with the need for repeat revascularization. In conclusion, STEMI was associated with a higher likelihood of in-hospital death than was NSTEMI, but long-term outcomes after PCI were independent of MI type. At 1 year, associated co-morbidities were strongly associated with death and MI, whereas only angiographic characteristics predicted the need for repeat revascularization.

Gender-based outcomes in percutaneous coronary intervention with drug-eluting stents (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Gender-based outcomes have not been evaluated in unselected patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). We investigated whether gender influences the relative safety and efficacy of DESs compared with bare metal stents (BMSs) in routine clinical practice. Using the National Heart, Lung, and Blood Institute Dynamic Registry, in-hospital and 1-year outcomes were stratified by gender in patients who received > or =1 DES (486 women, 974 men) or BMS (631 women, 1,132 men). There were significant baseline differences by gender, including older age and a higher prevalence of co-morbidities in women and more previous coronary artery disease in men. There were no gender-related differences in in-hospital myocardial infarction, coronary artery bypass grafting, and death in those treated with BMSs or DESs. Antiplatelet use and stent thrombosis (1.3% of women vs 1.2% of men, p = 0.85) were similar at 1 year with DESs. At 1 year, patients with DESs had a lower rate of repeat PCI (14.1% in women vs 9.5%, p = 0.02; 12.0% in men vs 8.8%, p = 0.02). Adjusted 1-year outcomes in patients with BMSs and DESs, including death and myocardial infarction, were independent of gender. Use of DESs was the only factor, other than age, that conferred a lower risk for the need for repeat PCI in women (relative risk 0.61, 95% confidence interval 0.41 to 0.89, p = 0.01) and men (relative risk 0.68, 95% confidence interval 0.51 to 0.91, p = 0.001). In conclusion, the widespread use of DESs is safe and has decreased clinically driven revascularization compared with BMSs equally in women and men.

Outcomes and complications associated with off-label and untested use of drug-eluting stents.

CONTEXT: Limited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings. OBJECTIVES: To determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI). DESIGN, SETTING, AND PATIENTS: Observational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort. MAIN OUTCOME MEASURES: Frequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up. RESULTS: Of 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]). CONCLUSIONS: In contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.

An Aggregate Biomarker Risk Score Predicts High Risk of Near-Term Myocardial Infarction and Death: Findings From BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes).

BACKGROUND: In a previous study, we found that a biomarker risk score (BRS) comprised of C-reactive protein, fibrin-degradation products, and heat shock protein-70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS, and (3) elucidate whether an altered BRS parallels altered risk. METHODS AND RESULTS: Two thousand thirty-two subjects with coronary artery disease were followed for 5.3±1.1 years for cardiovascular events. Biomarkers were measured at baseline and retested in 1304 subjects at 1 year. BRS was determined as the biomarker number above previously defined cut-off values (C-reactive protein >3 mg/L, heat shock protein-70 >0.313 ng/mL, and fibrin-degradation products >1 µg/mL). After adjustment for covariates, those with a BRS of 3 had a 4-fold increased risk of all-cause death and a 6.8-fold increased risk of cardiac death compared with those with a BRS of 0 (95% CI, 2.9-16.0; P<0.0001). All individual biomarkers decreased by 1 year, with ≈80% of patients decreasing their BRS. BRS recalibrated at 1 year also predicted risk. Those with 1-year BRS of 2 to 3 had a 4-year mortality rate of 21.1% versus 7.4% for those with BRS of 0 to 1 (P<0.0001). CONCLUSIONS: Our results validate the ability of the BRS to identify coronary artery disease patients at very high near-term risk of myocardial infarction/death. After 1 year of intensive medical therapy, the BRS decreased significantly, and the reclassified BRS continued to track with risk. Our results suggest that repeated BRS measurements might be used to assess risk and recalibrate therapy.

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial.

BACKGROUND: The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. OBJECTIVES: This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. METHODS: Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. RESULTS: A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p < 0.001). Among patients with low SYNTAX scores (≤22), major cardiovascular events did not differ significantly between revascularization and medical therapy, either in the CABG stratum (26.1% vs. 29.9%, p = 0.41) or in the PCI stratum (17.8% vs. 19.2%, p = 0.84). Among patients with mid/high SYNTAX scores, however, major cardiovascular events were lower after revascularization than with medical therapy in the CABG stratum (15.3% vs. 30.3%, p = 0.02), but not in the PCI stratum (35.6% vs. 26.5%, p = 0.12). CONCLUSIONS: Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).