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.

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.

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.

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).

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.

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).

Medical Treatment and Revascularization Options in Patients With Type 2 Diabetes and Coronary Disease.

BACKGROUND: There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF). OBJECTIVES: This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement. METHODS: A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy. RESULTS: Among 5,034 subjects, 15% had LVEF <50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT. CONCLUSIONS: CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.

Sex Differences in Outcomes Following Percutaneous Coronary Intervention According to Age.

BACKGROUND: Women <50 years of age with coronary artery disease may represent a group at higher risk for recurrent ischemic events after percutaneous coronary intervention (PCI); however, no long-term, multicenter outcomes assessment exists in this population. METHODS AND RESULTS: Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated the association of sex and age on cardiovascular-related outcomes in 10,963 patients (3797 women, 394 <50 years) undergoing PCI and followed for 5 years. Death, myocardial infarction, coronary artery bypass graft surgery, and repeat PCI were primary outcomes comprising major adverse cardiovascular events. Although procedural success rates were similar by sex, the cumulative rate of major adverse cardiovascular events at 1 year was higher in young women (27.8 versus 19.9%; P=0.003), driven largely by higher rates of repeat revascularizations for target vessel or target lesion failure (coronary artery bypass graft surgery: 8.9% versus 3.9%, P<0.001, adjusted hazard ratio 2.4, 95% confidence interval 1.5-4.0; PCI: 19.0% versus 13.0%, P=0.005, adjusted hazard ratio 1.6, 95% confidence interval 1.2-2.2). At 5 years, young women remained at higher risk for repeat procedures (coronary artery bypass graft surgery: 10.7% versus 6.8%, P=0.04, adjusted hazard ratio 1.71, 95% confidence interval 1.01-2.88; repeat PCI [target vessel]: 19.7% versus 11.8%, P=0.002, adjusted hazard ratio 1.8, 95% confidence interval 1.24-2.82). Compared with older women, younger women remained at increased risk of major adverse cardiovascular events, whereas all outcome rates were similar in older women and men. CONCLUSIONS: Young women, despite having less severe angiographic coronary artery disease, have an increased risk of target vessel and target lesion failure. The causes of this difference deserve further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005677.

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 long-term safety and efficacy outcomes after drug-eluting and bare-metal stent use across racial groups: Insights from NHLBI Dynamic Registry.

BACKGROUND: Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. METHODS: Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3326 patients who underwent PCI with DES versus BMS were evaluated. RESULTS: With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25-0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51-0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60-0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39-1.13, p=0.13). CONCLUSION: The use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents.

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.

Benefit of long-term dual anti-platelet therapy in patients treated with drug-eluting stents: from the NHLBI dynamic registry.

The optimal duration of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important, unanswered question. This study was designed to evaluate the association of varying durations of DAPT on clinical outcomes after DES implantation for the treatment of coronary artery disease. Using the National Heart, Lung, and Blood Institute Dynamic Registry, patients enrolled in the last 2 waves after index percutaneous coronary intervention with DES and who were event free at the time of landmark analysis were included. Landmark analysis was performed 12 and 24 months after percutaneous coronary intervention, and patients were stratified according to continued use of DAPT or not. Subjects were evaluated for rates of death, myocardial infarction, and stent thrombosis at 4 years from their index procedures. The numbers of evaluable patients were 2,157 and 1,918 for the 12- and 24-month landmarks, respectively. In both landmark analyses, there was a significantly lower 4-year rate of death or myocardial infarction in the group that continued DAPT compared to the group that did not (12 months: 10.5% vs 14.5%, p = 0.01; 24 months: 5.7% vs 8.6%, p = 0.02). Beneficial differences in the group that continued on DAPT were preserved after multivariate and propensity adjustment. There were no significant differences in definite stent thrombosis in either landmark analysis. In conclusion, at 12 and 24 months after DES implantation, continued use of DAPT was associated with lower 4-year risk for death and myocardial infarction.

Clinical presentation and predictors of target vessel revascularization after drug-eluting stent implantation.

BACKGROUND: Drug eluting stent (DES) failure including restenosis and stent thrombosis, or disease progression may result in target vessel revascularization (TVR) but the relative contribution of these mechanisms in the DES era is not well described. We sought to examine the predictors and presentations of patients with clinically driven TVR after DES. METHODS: Patients with all lesions treated with a DES in the Dynamic Registry from 2004 to 2006 were analyzed. Included were 2691 patients with 3401 lesions. Patients with and without incident clinically driven TVR at 2years were compared according to baseline clinical, procedural, and angiographic characteristics and independent predictors of TVR and target lesion revascularization (TLR) were determined by multivariate analysis. RESULTS: By 2-years, TVR occurred in 7.2% of patients and TLR in 3.8%, with 71.6% and 82.5% of repeat revascularization events occurring in the first year, respectively. The indication for first TVR was myocardial infarction in 18.6% (n=34), unstable angina in 42.6% (n=78), stable coronary disease in 25.7% (n=47) and other/unknown in 13.1% (n=24). Disease progression was responsible for 47% of TVR. Among patients with TLR, restenosis was the mechanism in 86.6% and stent thrombosis in 13.4%. Independent predictors of TVR included younger age, diabetes, attempted graft lesion, lesion length >30mm and prior lesion intervention. Independent predictors of TVR and TLR were similar. CONCLUSION: The incidence of clinically driven TVR is low in patients treated with DES and nearly half is attributable to disease progression, which along with the low rate of in-stent restenosis explains why the mode of presentation is often an acute coronary syndrome.

Comparison of bare-metal stents and drug-eluting stents in coronary ostial lesions (from the National Heart, Lung, and Blood Institute Dynamic Registry).

We compared the effectiveness of drug-eluting stents (DESs) to bare-metal stents (BMSs) in ostial lesions from an unrestricted patient cohort with 3-year follow-up. DESs have proved more effective at decreasing repeat revascularization rates compared to BMSs in patients with uncomplicated coronary artery disease. Whether DESs provide similar benefits in ostial lesions is not clearly defined. We analyzed data from 775 patients in the National, Heart, Lung, and Blood Institute Dynamic Registry undergoing stenting of ostial lesions with DESs or BMSs. Patients were followed for 3 years for the occurrence of myocardial infarction (MI), repeat revascularization (coronary bypass surgery/repeat percutaneous coronary intervention), and death. In total 439 patients had 464 ostial lesions treated with BMSs and 336 patients had 351 ostial lesions treated with DESs. Adjusted DES versus BMS 3-year hazard ratios were 1.03 (95% confidence interval 0.60 to 1.78, p = 0.90) for death, 1.40 (0.83 to 2.37, p = 0.21) for MI, and 0.81 (0.59 to 1.11, p = 0.19) for repeat revascularization. In patients undergoing percutaneous coronary intervention for aorto-ostial disease (n = 200), death and repeat revascularization did not differ between stent types, but DES-treated patients had more MI during follow-up. For coronary ostial disease (n = 574), 3-year observed rates of death or MI did not differ; however, repeat revascularization was more common in the BMS group. In conclusion, use of DESs for ostial lesions was associated with no difference in the hazard of death, MI, or overall rates of repeat revascularization compared to BMS use.

Outcomes of drug-eluting stents for protected left main coronary artery disease (from the Multicenter, United States DEScover registry).

Percutaneous coronary intervention (PCI) for protected left main coronary artery (PLM) disease is complex because of patient and lesion factors; however, limited data exist on the outcomes of drug-eluting stent (DES) use for this indication. DEScover is a prospective observational study that enrolled consecutive patients with PCI in 2005. In-hospital and 1-year statuses were analyzed for 6,172 patients treated with DES according to LM and coronary artery bypass grafting (CABG) statuses (PLM, n = 93; previous CABG native vessel non-LM, n = 722; no previous CABG, n = 5,357). Cumulative event rates were calculated by the Kaplan-Meier method. Cox proportional hazards regression was used for multivariable analysis of adverse events. Baseline clinical, angiographic, and procedural variables differed significantly among groups, with patients with previous CABG, PLM, and non-LM having higher risk characteristics. In patients with previous CABG, after adjustment with CABG non-LM as a reference group, there were no significant differences in 1-year risk of any adverse event except a trend toward a greater risk of myocardial infarction (MI) in patients with PLM (adjusted hazard ratio 2.4, confidence interval 0.95 to 6.2, p = 0.06). However, patients after CABG (PLM and non-LM) compared to patients without previous CABG had a similar adjusted risk of death, MI, and stent thrombosis; an increased risk of target lesion revascularization (adjusted hazard ratio 1.79, confidence interval 1.2 to 2.6, p = 0.003), target vessel revascularization and death/MI/target vessel revascularization; and a lower risk of CABG (adjusted hazard ratio 0.25, confidence interval 0.09 to 0.67, p = 0.006). In conclusion, status after CABG rather than PLM location increases the risk of repeat revascularization with PCI in DES-treated patients.