Clinical and angiographic risk stratification and differential impact on treatment outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

BACKGROUND: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata. METHODS AND RESULTS: An angiographic risk score was developed from variables assessed at randomization; independent prognostic factors were myocardial jeopardy index, total number of coronary lesions, prior coronary revascularization, and left ventricular ejection fraction. The Framingham Risk Score for patients with coronary disease was used to summarize clinical risk. Cardiovascular event rates were compared by assigned treatment within high-risk and low-risk subgroups. Overall, no outcome differences between the intensive medical therapy and prompt coronary revascularization groups were seen in any risk stratum. The 5-year risk of death/myocardial infarction/stroke was 36.8% for intensive medical therapy compared with 24.8% for prompt coronary revascularization among the 381 coronary artery bypass graft surgery-selected patients in the highest angiographic risk tertile (P=0.005); this treatment effect was amplified in patients with both high angiographic and high Framingham risk (47.3% intensive medical therapy versus 27.1% prompt coronary revascularization; P=0.010; hazard ratio=2.10; P=0.009). Treatment group differences were not significant in other clinical-angiographic risk groups within the coronary artery bypass graft surgery stratum, or in any subgroups within the percutaneous coronary intervention stratum. CONCLUSION: Among patients with diabetes mellitus and stable ischemic heart disease, a strategy of prompt coronary artery bypass graft surgery significantly reduces the rate of death/myocardial infarction MI/stroke in those with extensive coronary artery disease or impaired left ventricular function. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Direct comparison of Takotsubo cardiomyopathy between Japan and USA: 3-year follow-up study.

OBJECTIVE: Takotsubo cardiomyopathy (TC) mimics myocardial infarction and is well defined and known to not only Japan but also western countries. However, whether or not there are differences in the characteristics of TC between Japan and USA remains unknown. PATIENTS: Data for patients who had undergone urgent left heart catheterization for suspected acute coronary syndrome were retrospectively retrieved from Keio University School of Medicine (KUSM) database in Japan and Lahey Clinic Medical Center (LCMC) database in USA between 2002 and 2007. RESULTS: During the study period, 626 coronary angiographies were performed in KUSM and 1,880 coronary angiographies were performed in LCMC. Twelve patients in Japan and 34 patients in USA met the inclusion criteria. Mean age of patients in Japan was 75 years where 92% were women, compared to 67 years and 94% women in USA. Although the prevalence of hypertension, dyslipidemia and diabetes mellitus were similar between Japan and USA, there was a trend towards fewer patients in Japan displaying a history of coronary revascularization. Surprisingly, a family history of premature coronary artery disease (CAD) was present in 21% of USA patients, whereas no patients were present in Japan. There were no differences in the incidence of readmission for heart failure, cardiac death and TC recurrence during the follow-up period. CONCLUSION: Patients with TC in Japan have fewer prior overt CAD and fewer family history of premature CAD, but no significant differences were found in the long-term prognosis and the recurrence rate between patients in Japan and USA.

Presentation in patients with angiographically documented coronary artery disease and type II diabetes mellitus (from the BARI 2D Clinical Trial).

Clinically stable patients with type 2 diabetes mellitus and coronary artery disease are not often thought to present with the symptom of typical angina. The aims of this study were to enumerate the proportion of patients presenting with typical angina or other cardiac symptoms and to elucidate what important clinical variables are associated with the presence of typical angina in patients with type 2 diabetes mellitus and angiographically documented coronary artery disease. Symptoms of angina, anginal equivalents, or an absence of symptoms were obtained using baseline data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial (n = 2,319). A bivariate analysis stratified by the presence or absence of previous revascularization and logistic regression modeling with a stepwise covariate selection was used. Eighty-two percent of patients had symptoms, while 18% presented asymptomatically. This was further divided approximately into typical angina (1/5), anginal equivalents (1/5), combination (2/5), and asymptomatic (1/5). A history of previous revascularization was a determinant of the type of symptom presentation with regard to the variables gender, age, current insulin use, myocardial jeopardy index score, and use of ß blockers. In the multivariate logistic regression analysis, of the available candidate variables, only a history of ß-blocker use (odds ratio 1.53, 95% confidence interval 1.24 to 1.94, p <0.0001) and previous percutaneous coronary intervention (odds ratio 1.55, 95% confidence interval 1.24 to 1.94, p <0.0001) had higher odds of an association with typical angina. In conclusion, a large proportion of patients with type 2 diabetes mellitus and coronary artery disease indeed have symptoms. Future studies of long-term outcomes associated with these symptoms are needed.

Evaluation of in-stent restenosis in the APPROACH trial (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History).

To determine (1) the medium-term effect of rosiglitazone and glipizide on intra-stent neointima hyperplasia, (2) restenosis pattern as assessed by intra-vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) in patients with T2DM and coronary artery disease. A total of 462 patients with T2DM were randomized to rosiglitazone or glipizide for up to 18 months in the APPROACH trial, and had evaluable baseline and follow-up IVUS examinations. There was no significant difference in the size of plaque behind stent between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (-5.6 mm(3) vs. 1.9 mm(3); P = 0.61) or with a drug-eluting stent (12.1 mm(3) vs. 5.5 mm(3); P = 0.09). Similarly, there was no significant difference in percentage intimal hyperplasia volume between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (24.1% vs. 19.8%; P = 0.38) or with a drug-eluting stent (9.8% vs. 8.3%; P = 0.57). QCA data (intra-stent late loss, intra-stent diameter stenosis or binary restenosis) were not different between the rosiglitazone and glipizide groups. This study suggests that both rosiglitazone and glipizide have a similar effect on neointimal growth at medium term follow-up, a finding that warrants investigation in dedicated randomized trials.

Blood pressure, lipids and glucose in type 2 diabetes: how low should we go? Re-discovering personalized care.

Epidemiological studies have clearly shown a direct relationship between the levels of blood pressure, glycaemia and LDL-cholesterol, and the complications of diabetes. Although 'lower should be better', the results of recent clinical trials examining the benefits of normalizing risk factor levels have been counter-intuitive and, at times, disturbing, and have called into question this notion. This review focuses on patients with type 2 diabetes who make up 90% of patients with diabetes. It aims to provide a clear summary and interpretation of recent trials to help clinicians to set targets for cardiovascular risk factors in individual patients. It highlights areas of agreement and disagreement between current guidelines. Recent data indicate that some patient subgroups might respond differently to aggressive risk factor management. Our challenge is how to identify these patients and deliver truly personalized diabetes care that maximizes benefit, and minimizes harm. Guidelines and position statements stress the value of setting personalized targets. We explore what this means, and how this might be achieved in practice by outlining some solutions to issues that currently limit the delivery of personalized care. We call for further research assessing the overall clinical impact of cardiovascular risk factor intervention by finding appropriate ways of combining data on mortality, complications, side-effects, quality of life, and cost-effectiveness.

Cardiac resynchronization therapy reduces the risk of cardiac events in patients with diabetes enrolled in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT).

BACKGROUND: Data are limited regarding whether the presence of diabetes mellitus (DM) influences the benefit of cardiac resynchronization with defibrillator therapy (CRT-D) in heart failure (HF) patients. METHODS AND RESULTS: The effect of CRT-D was evaluated in 1817 patients who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Patients were minimally symptomatic (New York Heart Association class I or II), with ejection fraction ≤0.30 and QRS ≥130 ms. We used Cox regression to determine hazard ratio (HR) of CRT-D versus implantable cardioverter-defibrillator (ICD) therapy for the risk of HF event or death, whichever came first (MADIT-CRT primary end point), in DM (n=552) and non-DM (n=1265) patients. Compared with the non-DM patients, those with DM had more coronary risk factors. During an average follow-up of 2.4 years, DM patients had significantly more primary end point events than non-DM patients (26.6% versus 18%, P<0.001). CRT-D was associated with a significant reduction in risk of primary end point in both DM (HR=0.56, P<0.001) and non-DM patients (HR=0.67, P=0.003). Compared with non-DM patients, CRT-D:ICD HRs in DM patients were lower in the total population, and in subgroups with ischemic cardiomyopathy (0.63 versus 0.64), nonischemic cardiomyopathy (0.39 versus 0.73), and left bundle-branch block (0.36 versus 0.50). There were no significant differences in ventricular remodeling, arrhythmia events, or device-related complications between DM and non-DM patients. CONCLUSIONS: Patients with diabetes, left ventricular dysfunction, mildly symptomatic HF, and wide QRS complex derive similar benefit from CRT-D compared with patients without diabetes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

The prevalence and predictors of an abnormal ankle-brachial index in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

OBJECTIVE: To examine ankle-brachial index (ABI) abnormalities in patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: An ABI was obtained in 2,240 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. ABIs were classified as: normal, 0.91-1.3; low, ≤ 0.9; high, >1.3; or noncompressible artery (NC). Baseline characteristics were examined according to ABI and by multivariate analysis. RESULTS ABI was normal in 66%, low in 19%, and high in 8% of patients, and 6% of patients had NC. Of the low ABI patients, 68% were asymptomatic. Using normal ABI as referent, low ABI was independently associated with smoking, female sex, black race, hypertension, age, C-reactive protein, diabetes duration, and lower BMI. High ABI was associated with male sex, nonblack race, and higher BMI; and NC artery was associated with diabetes duration, higher BMI, and hypertension. CONCLUSIONS: ABI abnormalities are common and often asymptomatic in patients with type 2 diabetes and CAD.

Resting heart rate and metabolic syndrome in patients with diabetes and coronary artery disease in bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial.

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4+/-12.3 vs 65.6+/-11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.

Evolution of percutaneous coronary intervention in patients with diabetes: a report from the National Heart, Lung, and Blood Institute-sponsored PTCA (1985-1986) and Dynamic (1997-2006) Registries.

OBJECTIVE: To evaluate the association of successive percutaneous coronary intervention (PCI) modalities with balloon angioplasty (BA), bare-metal stent (BMS), drug-eluting stents (DES), and pharmacotherapy over the last 3 decades with outcomes among patients with diabetes in routine clinical practice. RESEARCH DESIGN AND METHODS: We examined outcomes in 1,846 patients with diabetes undergoing de novo PCI in the multicenter, National Heart, Lung, and Blood Institute-sponsored 1985-1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry and 1997-2006 Dynamic Registry. Multivariable Cox regression models were used to estimate the adjusted risk of events (death/myocardial infarction [MI], repeat revascularization) over 1 year. RESULTS: Cumulative event rates for postdischarge (31-365 days) death/MI were 8% by BA, 7% by BMS, and 7% by DES use (P = 0.76) and for repeat revascularization were 19, 13, and 9% (P < 0.001), respectively. Multivariable analysis showed a significantly lower risk of repeat revascularization with DES use when compared with the use of BA (hazard ratio [HR] 0.41 [95% CI 0.29-0.58]) and BMS (HR 0.55 [95% CI 0.39-0.76]). After further adjustment for discharge medications, the lower risk for death/MI was not statistically significant for DES when compared with BA. CONCLUSIONS: In patients with diabetes undergoing PCI, the use of DES is associated with a reduced need for repeat revascularization when compared with BA or BMS use. The associated death/MI benefit observed with the DES versus the BA group may well be due to greater use of pharmacotherapy.

The BARI 2D study: a randomised trial of therapies for type 2 diabetes and coronary artery disease.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized 2368 patients with type 2 diabetes (T2DM) and coronary artery disease to either prompt revascularization or intensive medical therapy alone; and to either insulin-sensitization or insulin-provision diabetes therapy. Randomization was stratified by proposed revascularization method. Five-year survival and major cardiovascular events (MACE) were similar in study subgroups except in the coronary bypass surgery (CABG) stratum where there were fewer MACE after revascularization. There was less hypoglycaemia and weight gain, and greater apparent benefit from CABG in the insulin sensitization group. BARI 2D has provided important data for clinicians.

Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial.

BACKGROUND: Rosiglitazone has several properties that may affect progression of atherosclerosis. The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide. METHODS AND RESULTS: This was a randomized, double-blind, controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle, 1 oral agent, or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10% to 50% luminal narrowing in a coronary artery that had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention. The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention. Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment. Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide (-0.64%; 95% confidence interval, -1.46 to 0.17; P=0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (-5.1 mm(3); 95% confidence interval, -10.0 to -0.3; P=0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (-1.7 mm(3); 95% confidence interval, -3.9 to 0.5; P=0.13). CONCLUSIONS: Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00116831.

Relationships of obesity and fat distribution with atherothrombotic risk factors: baseline results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non-Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs. non-US site, diabetes duration, exercise, smoking, alcohol, and relevant medication use. First-order partial correlations of BMI with risk factors after controlling for waist circumference and of waist circumference with risk factors after controlling for BMI were also evaluated. Ninety percent of the patients were overweight (BMI > or =25 kg/m(2)); 68% of men and 89% of women had high-risk waist circumference measures (> or =102 and > or =88 cm, respectively). BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C-reactive protein, PAI-1 activity and antigen, and fibrinogen) risk factors. In partial correlation analyses BMI was independently associated with BP and inflammatory/procoagulation factors, waist circumference with lipids, and both BMI and waist circumference with insulin. We conclude that, in cross-sectional analyses, both BMI and waist circumference, independently, are associated with increased atherothrombotic risk in centrally obese cohorts such as the BARI 2D patients with T2DM and CAD.

Guiding clinical decisions on abdominal obesity and cardiometabolic risk.

Studies have shown that obesity increases cardiometabolic risk across the span of life. Obesity results in increased production of proinflammatory adipokines and decreased production of the anti-inflammatory adipokine, adiponectin, which eventually leads to atherosclerosis and type 2 diabetes mellitus. Lifestyle changes are the cornerstone for treatment of overweight and obese patients; however, pharmacotherapy and surgery are 2 additional treatment options that may be considered when lifestyle changes alone are unsuccessful. Adipose tissue, particularly central adipose tissue, is an endocrine organ, the actions of which tie together all components of cardiometabolic risk. Weight loss reduces levels of most proinflammatory adipokines, attenuates inflammation, improves endothelial function, and enhances insulin sensitivity. In view of these effects, obesity represents an obvious target for pharmacologic intervention. However, the benefits associated with the pharmacologic management of weight loss must be weighed against the potential for drug-related adverse events.

Influence of diabetes and/or myocardial infarction on prevalence of abnormal T-wave alternans.

BACKGROUND: Subjects with microvolt-level T-wave alternans (TWA) in association with structural heart disease have an increased risk for sudden cardiac death. The presence of diabetes (DM) is associated with an increased risk of sudden death but there is limited data on the impact of DM and previous myocardial infarction (MI) on TWA prevalence. METHODS: We performed a case-control cross-sectional study in 140 patients referred for routine exercise testing within a large multispecialty clinic. All patients with a history of DM and MI status within the past year were eligible: group 1 (no DM or MI), group 2 (DM only), group 3 (MI only), group 4 (DM and MI). Patients performed a symptom-limited Bruce protocol exercise test with assessment of TWA by the spectral method using commercially available equipment. We used published criteria for the blinded interpretation of TWA; all tests not unequivocally negative were considered abnormal. RESULTS: Age and gender were similar in all groups. The prevalence of abnormal TWA in groups 1-4 was 24%, 20%, 48%, and 62%, respectively (between group P = 0.002). Logistic regression analysis in all patients showed that abnormal TWA was related to prior MI [OR (95% CI): 4.0 (1.8-8.9), P < 0.001] but not to prevalent DM [0.9 (0.4-1.8), P = 0.72]. In patients with DM, the prevalence of abnormal TWA was related to reduced ejection fraction (P = 0.034) but not to BMI, DM duration, glycemic control, insulin use, or the presence of microvascular complications. CONCLUSION: The presence of DM alone does not increase risk of abnormal TWA. Prospective studies are required to establish the prognostic value of TWA in patients with DM.

Comparison of incidence of acute myocardial infarction in patients with type 2 diabetes mellitus following initiation of neutral protamine Hagedorn insulin versus insulin glargine.

Recent reports have described different risks of acute myocardial infarction (AMI) in association with specific oral antidiabetic medications. The present study compared the AMI incidence rates in new users of traditional neutral protamine Hagedorn (NPH) insulin and a long-acting synthetic insulin analog for basal insulin therapy. We retrospectively examined in-patient medical claims for AMI in a cohort of oral agent-treated patients with type 2 diabetes mellitus after the initiation of basal insulin therapy with either NPH (n = 5,461) or insulin glargine (n = 14,730) in a national administrative claims database comprising >30 managed healthcare plans in the United States. Poisson regression and Cox proportional hazards regression models, as well as the propensity score methods, were used to compare the subsequent AMI incidence rates after the initiation of NPH or glargine. At a mean follow-up of 2 years, the unadjusted AMI incidence was 17.6/1,000 person-years after the initiation of NPH versus 11.5/1,000 person-years after initiation of glargine (rate ratio 1.53, 95% confidence interval 1.29 to 1.81). The Cox regression model (hazard ratio 1.39, 95% confidence interval 1.14 to 1.69) and sensitivity analyses (hazard ratio range 1.30 to 1.56) showed a greater risk of AMI in the NPH group than in the glargine group. Propensity matched (1:1) analysis yielded similar results (odds ratio 1.55, 95% confidence interval 1.23 to 1.96 for NPH vs glargine). In conclusion, these results suggest that the initiation of basal insulin therapy with NPH rather than glargine in patients with type 2 diabetes mellitus is associated with a greater risk of AMI.

Clinical characteristics of tako-tsubo cardiomyopathy.

Tako-tsubo cardiomyopathy (TTC) is increasingly diagnosed in the United States, especially in the Caucasian population. To evaluate the clinical features and outcome of patients with TTC, we evaluated 34 patients (32 women and 2 men) 22 to 88 years of age (mean 66 +/- 14) who fulfilled the following criteria: (1) akinesia or dyskinesia of the apical and/or midventricular segments of the left ventricle with regional wall motion abnormalities that extended beyond the distribution of a single epicardial vessel and (2) absence of obstructive coronary artery disease. Twenty-five patients (74%) presented with chest pain, 20 patients (59%) presented with dyspnea, and 8 patients (24%) presented with cardiogenic shock. Twenty-two patients (65%) had ST-segment elevation and 14 patients (41%) had T-wave inversion on presentation. Twenty-five patients (74%) reported a preceding stressful event. Cardiac biomarkers were often mildly increased, with a mean troponin I (peak) of 13.9 +/- 24. Mean +/- SD left ventricular ejection fractions were 28 +/- 10% at time of presentation and 51 +/- 14 at time of follow-up (p <0.0001). Two patients (6%) died during the hospital stay. Average duration of hospital stay was 6.6 +/- 6.2 days. In conclusion, TTC is common in postmenopausal women with preceding physical or emotional stress. It predominantly involves the apical portion of the left ventricle and patients with this condition have a favorable outcome with appropriate medical management. The precise cause remains unclear.

In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study.

OBJECTIVES: To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device. BACKGROUND: An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients. METHODS: Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra. RESULTS: A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis. Spectra from 30 patients were unblinded to test the calibration of the LCP detection algorithm. Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts. CONCLUSIONS: This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system. (SPECTACL: SPECTroscopic Assessment of Coronary Lipid; NCT00330928).

A randomized trial of therapies for type 2 diabetes and coronary artery disease.

BACKGROUND: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. METHODS: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention. RESULTS: At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003). CONCLUSIONS: Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)