BARI 2D Research Articles

Quality of Life in Older Adults With Stable Ischemic Heart Disease and Diabetes Mellitus: A Post Hoc Analysis of the BARI 2D Trial

Studies on the long-term differences in quality-of-life (QoL) metrics after treatment for stable ischemic heart disease (SIHD) in older adults with diabetes mellitus are lacking. Older patients (age ≥65 years) in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial were stratified into those who received intensive medical therapy (IMT) only versus revascularization (percutaneous coronary intervention [PCI] vs coronary artery bypass graft surgery [CABG]) with Optimal Medical Therapy (OMT). Self-health score, Duke activity status index (DASI), energy rating, and health distress rating at 5 years were compared using multivariable linear regression. A total of 929 older adults were included, of whom 469 (50.5%) underwent medical therapy alone, 302 (32.5%) underwent PCI, and 158 (17.0%) had CABG. Patients who underwent CABG were more likely to have proximal left anterior descending coronary artery disease, chronic total occlusion, and higher myocardial jeopardy index. At 5 years of follow-up, no differences in self-health score, DASI, energy rating, and health distress rating were observed between PCI and IMT. There are also no differences in the 4 QoL measures between CABG and IMT alone. However, the DASI was marginally higher with CABG but not statistically significant (mean difference 3.88, 95% confidence interval -0.10 to -7.86, p = 0.057). At 5 years of follow-up, no differences in QoL measures were observed between PCI and CABG with OMT versus OMT alone in older adult patients with diabetes mellitus and SIHD. Future blinded randomized trials are necessary to investigate the impact of SIHD treatment in the older adult population, considering the risks associated with multimorbidity, polypharmacy, frailty, and cognitive impairment.

Do Clinical Outcomes and Quality of Life Differ by the Number of Antianginals for Stable Ischemic Heart Disease? Insights from the BARI 2D Trial

Medical therapy, including antianginal treatment, is the cornerstone in the management of stable ischemic heart disease (SIHD). However, it remains unclear whether combining antianginal agents provides benefits beyond monotherapy in terms of quality of life (QoL) and cardiovascular outcomes. We used data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, which compared cardiovascular and QoL outcomes in patients with SIHD and diabetes mellitus randomized to revascularization with intensive medical therapy or intensive medical therapy alone. We categorized patients into 3 groups: ≥2 versus 1 versus 0 antianginals. We compared patient characteristics, QoL metrics, and cardiovascular end points at baseline and at 5 years, creating a multivariable model to adjust for key clinical confounders. Of 2,368 patients, 348 patients (14.7%) were on 0 antianginals, 1,020 patients (43.1%) were on 1 antianginal, and 1,000 patients (42.2%) were on ≥2 antianginals at baseline. The most common antianginal class was β blockers. At baseline, patients on 0 antianginals had better QoL metrics (self-health score, Duke activity status index, and energy rating) than patients on ≥2 antianginals. However, at the 1-year follow-up, patients taking only 1 antianginal showed greater QoL improvement than those taking 0 antianginal, without any incremental benefit in QoL metrics seen in patients taking ≥2 antianginal agents, even after adjusting for multiple covariates such as age, heart failure, diabetes control, and myocardial jeopardy index. Lastly, at the 5-year follow-up, after adjustment, there were no differences in all-cause mortality, major adverse cardiovascular events, or myocardial infarction between patients taking different numbers of antianginals. Adults on a single antianginal for SIHD and diabetes mellitus had similar or better improvements in QoL than those on 2 or more antianginal agents at 1 year of follow-up. These findings merit further research to better understand the impact of medical therapy intensity on QoL in patients with SIHD and associated co-morbidities.

Optimal Medical Therapy as First-Line Therapy for Chronic Coronary Syndromes: Lessons from COURAGE, BARI 2D, FAME 2, and ISCHEMIA.

The chronic coronary syndromes (CCS) include patients with a classic history of angina pectoris in the presence of either risk factors for or known atherosclerotic coronary artery disease. Randomized, controlled trials conducted in the optimal medical therapy (OMT) era have convincingly demonstrated that adherence to the outdated paradigm focused on treatment of obstructive coronary disease with initial revascularization fails to reduce death or myocardial infarction and inconsistently reduces angina symptoms. Rather, OMT reduces events and improves symptoms and should be considered first-line treatment for patients with CCS.

Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes.

Type 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies. Participants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study (N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was compared. Clustering variables included demographics, medical and social history, laboratory values and diabetes complications. The interaction between the phenogroup and intensive glycaemic, combination lipid and intensive BP therapy for the risk of the primary outcome (composite of fatal myocardial infarction, non-fatal myocardial infarction or unstable angina) was evaluated using adjusted Cox models. The phenomapping strategies were independently assessed in an external validation cohort (Look Action for Health in Diabetes [Look AHEAD] trial: n = 4211; and Bypass Angioplasty Revascularisation Investigation 2 Diabetes [BARI 2D] trial: n = 1495). Over 9.1years of follow-up, 789 (12.2%) participants had a primary outcome event. FMM phenomapping with three phenogroups was the best-performing clustering strategy in both the derivation and validation cohorts as determined by Bayesian information criterion, Dunn index and improvement in model discrimination. Phenogroup 1 (n = 663, 10.3%) had the highest burden of comorbidities and diabetes complications, phenogroup 2 (n = 2388, 36.9%) had an intermediate comorbidity burden and lowest diabetes complications, and phenogroup 3 (n = 3415, 52.8%) had the fewest comorbidities and intermediate burden of diabetes complications. Significant interactions were observed between phenogroups and treatment interventions including intensive glycaemic control (p-interaction = 0.042) and combination lipid therapy (p-interaction < 0.001) in the ACCORD, intensive lifestyle intervention (p-interaction = 0.002) in the Look AHEAD and early coronary revascularisation (p-interaction = 0.003) in the BARI 2D trial cohorts for the risk of the primary composite outcome. Favourable reduction in the risk of the primary composite outcome with these interventions was noted in low-risk participants of phenogroup 3 but not in other phenogroups. Compared with phenogroup 3, phenogroup 1 participants were more likely to have severe/symptomatic hypoglycaemic events and medication non-adherence on follow-up in the ACCORD and Look AHEAD trial cohorts. Clustering using FMMs was the optimal phenomapping strategy to identify replicable subgroups of patients with type 2 diabetes with distinct clinical characteristics, CVD risk and response to therapies.

Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial)

Triglyceride (TG) levels encompass several lipoproteins that have been implicated in atherogenic pathways. Whether TG levels independently associate with cardiovascular disease both overall and, in particular among patients with established coronary artery disease (CAD) and type 2 diabetes (T2DM), remains controversial. Data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was used to evaluate patients with T2DM and CAD. Cox proportional hazards models were used to determine the association between TG levels and outcomes. Stepwise adjustment was performed for demographics, clinical factors, lipid profile and statin treatment. The primary composite outcome was time to CV death, myocardial infarction (MI), or stroke and secondary outcome was CV death. Among 2,307 patients with T2DM and CAD, the mean (±SD) TG levels were 181 (±136) with a median (Q1-Q3) 148mg/dL (104-219). Overall, 51% of patients had TG <150 mg/dL, 18% 150-199 mg/dL, 28% 200-499 mg/dL and 3% ≥500 mg/dL. Participants with elevated TG levels (≥150 mg/dL) were younger (61 vs 63 years, p <0.001), had higher BMI (32 vs 30 kg/m2, p <0.001), more likely to have had prior MI (34.2 vs 30.1%, p = 0.033) and revascularization (25.8 vs 21.4%, p = 0.013), had lower HDL-C (34 vs 39 mg/dL, p <0.001) and higher HbA1c (8 vs 7%, p <0.001). In unadjusted analyses, baseline TG levels were linearly associated with both the primary composite and secondary outcomes. In fully adjusted analyses, every 50 mg/dL increase in TG level was associated with a 3.8% (HR 1.038, 95%CI 1.004-1.072, p <0.001) increase in the primary composite outcome and a 6.4% (HR 1.064 95%CI 1.018-1.113, p <0.001) increase in the secondary outcome. There was no interaction between TG and outcomes within key subgroups including female sex, additional non-coronary atherosclerotic disease, CKD or low LDL (<100 mg/dL). In conclusion, among patients with T2DM and CAD, elevated TG were independently associated with adverse cardiovascular outcomes, even after adjustment for clinical and simple biochemical covariates.

BARI 2D: A Reanalysis Focusing on Cardiovascular Events

ObjectiveTo 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 MethodsFrom 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. ResultsFour-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%). ConclusionIn 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 Registrationclinicaltrials.gov Identifier: NCT00006305

1472-P: Association between Triglycerides and Residual Cardiovascular (CVD) Risk in Patients with Type 2 Diabetes and Established CVD: An Analysis of the BARI2D Trial

Background: While hypertriglyceridemia is a known risk factor for developing CVD, whether it poses residual risk in patients with type 2 diabetes mellitus (T2DM) and established CVD is under-studied. Methods: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, we examined 2,307 patients with T2DM and CVD to determine the association of baseline fasting triglyceride (TG) levels with MACE (time to CV death, myocardial infarction (MI), or stroke) or CV death over a mean follow-up of 5.0 years. Results: At baseline, the mean fasting TG was 181 mg/dl with a median (Q1, Q3) of 148 (104, 219) mg/dl. Overall, 49.3% had TG≥ 150 mg/dl (N=1,167). Compared with those with TG&amp;lt;150 mg/dl, they were younger, more frequently Caucasian and with higher BMI. In unadjusted models, TGs were significantly associated with MACE and CV death (Table). This association did not remain after adjustment for multiple factors, including nonHDLc. Conclusions: In this analysis of patients with T2DM and known CVD, TGs were relatively high and were associated with CV outcomes, but not when other risk factors were taken into account. Thus, while TGs are clearly a marker of those with residual high risk for CV events in T2DM, whether they specifically need to be lowered awaits well conducted clinical trials. Disclosure N. Pagidipati: Research Support; Self; Amarin Corporation, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Regenerative Medical Solutions, Sanofi. A. Navar: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Amarin Corporation, Amgen Inc., Regeneron Pharmaceuticals, Sanofi. H. Mulder: None. D.M. Wojdyla: None. S. Philip: Employee; Self; Amarin Corporation. Stock/Shareholder; Self; Amarin Corporation. C.B. Granowitz: Employee; Self; Amarin Pharma Inc. Stock/Shareholder; Self; Amarin Pharma Inc. Funding Amarin Corporation

On-Pump Coronary Artery Bypass Graft: The State of the Art.

Coronary artery bypass grafting (CABG) remains the standard of care for patients with coronary artery disease (CAD). Debate exists concerning several factors, which include percutaneous coronary intervention (PCI) vs. CABG, single vs. bilateral mammary artery grafts, radial artery vs. saphenous vein grafts, right internal mammary artery vs. radial artery grafts, endoscopic vs. open vein-graft harvesting, and on-pump vs. off- pump surgery. Moreover, challenging is the management of diabetic patients with CAD undergoing CABG. This review reports current indications, practice patterns, and outcomes of CABG. Randomized controlled trials comparing CABG to other therapeutical strategies for CAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Large multicenter randomized and observational studies (SYNTAX, BEST, PRECOMBAT, ASCERT) have reported excellent outcomes in CABG patients, with always fewer rates of operative mortality and major morbidity, than PCI. The 10-year follow-up of ARTS II trial showed no difference between single and bilateral mammary artery. BARI 2D, MASS II, CARDia, FREEDOM trials showed that CABG is the best choice for diabetic patients. CABG still represents one of the most widespread major surgeries, with well-known benefits on symptoms and prognosis in patients with CAD. However, further studies and follow-up data are needed to validate these evidences.

A Genetic Locus on Chromosome 2q24 Predicting Peripheral Neuropathy Risk in Type 2 Diabetes: Results From the ACCORD and BARI 2D Studies.

Genetic factors have been postulated to be involved in the etiology of diabetic peripheral neuropathy (DPN), but their identity remains mostly unknown. The aim of this study was to conduct a systematic search for genetic variants influencing DPN risk using two well-characterized cohorts. A genome-wide association study (GWAS) testing 6.8 million single nucleotide polymorphisms was conducted among participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial. Included were 4,384 white case patients with type 2 diabetes (T2D) and prevalent or incident DPN (defined as a Michigan Neuropathy Screening Instrument clinical examination score >2.0) and 784 white control subjects with T2D and no evidence of DPN at baseline or during follow-up. Replication of significant loci was sought among white subjects with T2D (791 DPN-positive case subjects and 158 DPN-negative control subjects) from the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) trial. Association between significant variants and gene expression in peripheral nerves was evaluated in the Genotype-Tissue Expression (GTEx) database. A cluster of 28 SNPs on chromosome 2q24 reached GWAS significance (P < 5 × 10−8) in ACCORD. The minor allele of the lead SNP (rs13417783, minor allele frequency = 0.14) decreased DPN odds by 36% (odds ratio [OR] 0.64, 95% CI 0.55–0.74, P = 1.9 × 10−9). This effect was not influenced by ACCORD treatment assignments (P for interaction = 0.6) or mediated by an association with known DPN risk factors. This locus was successfully validated in BARI 2D (OR 0.57, 95% CI 0.42–0.80, P = 9 × 10−4; summary P = 7.9 × 10−12). In GTEx, the minor, protective allele at this locus was associated with higher tibial nerve expression of an adjacent gene (SCN2A) coding for human voltage-gated sodium channel NaV1.2 (P = 9 × 10−4). To conclude, we have identified and successfully validated a previously unknown locus with a powerful protective effect on the development of DPN in T2D. These results may provide novel insights into DPN pathogenesis and point to a potential target for novel interventions.

Optimal cardiac strategy based on the history of myocardial infarction in type 2 diabetic patients with coronary artery disease

The aim of this study was to evaluate the association between the cardiac treatment strategy and cardiac event risk in type 2 diabetic patients with coronary artery disease (CAD) based on the history of myocardial infarction. Using Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data, a Cox proportional hazard model was used for calculating hazard ratios (HRs) for major cardiac events in patients receiving early revascularization or intensive medical therapy. Patients without (n = 1,557) and with myocardial infarction (n = 736) were separately analyzed. In patients without myocardial infarction, risk of major cardiac events was similar for percutaneous coronary intervention and intensive medical therapy groups, whereas it was significantly lower in the coronary artery bypass grafting group than in the intensive medical therapy group (HR: 0.48, 95% confidence interval [95%CI]: 0.30–0.76, P = 0.002). Conversely, in patients with myocardial infarction, risk of major cardiac events was significantly higher in the early revascularization group than in the intensive medical therapy group (HR: 1.47, 95%CI: 1.03–2.11, P = 0.03). In type 2 diabetic patients with CAD, benefits of early revascularization were observed only in those without previous myocardial infarction. For patients with previous myocardial infarction, intensive medical therapy exerted superior benefits.

Development of a risk score to identify patients with type 2 diabetes mellitus and multivessel coronary artery disease who can defer bypass surgery

BackgroundCurrent American College of Cardiology/American Heart Association (ACC/AHA) guidelines provide a class I recommendation for patients with type 2 diabetes mellitus and multivessel coronary artery disease (CAD) to be treated with coronary artery bypass graft surgery (CABG). However, these patients are heterogeneous in terms of the risks and benefits associated with CABG. We sought to develop a risk score to identify low-risk patients with diabetes and multivessel CAD in whom CABG can be safely deferred.MethodsPatients in the CABG strata randomized to intensive medical therapy (IMT) in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial who experienced death, myocardial infarction (MI), or stroke were compared with those who did not. We developed a risk score for death, MI, or stroke using a Cox proportional hazards model that included the following variables: age, history of heart failure, history of hypercholesterolemia, history of stroke, transient ischemic attack, serum creatinine, insulin use, myocardial jeopardy index, and HbA1c.ResultsAmong patients with a risk score less than the median, those randomized to IMT or prompt CABG experienced similar rates of event-free survival at 5 years (77.8% vs. 83.2%, logrank P = 0.24). Among patients with a risk score greater than the median, those randomized to IMT experienced worse rates of event-free survival at 5 years than those randomized to prompt CABG (60.3% vs 73.2%, logrank P = 0.01).ConclusionsA novel risk score identifies low-risk patients with diabetes and stable, symptomatic multivessel CAD in whom CABG can be safely deferred.

Strategies for glycemic control in nonobese and obese type 2 diabetic patients with coronary artery disease

BackgroundThis study aimed to assess strategies of insulin-providing (IP) or insulin-sensitizing (IS) therapy for glycemic control in nonobese diabetic patients with coronary artery disease (CAD) with possibly higher cardiovascular risk and lower insulin secretion than obese diabetic patients with CAD. MethodsWe used data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial to calculate hazard ratio (HR) with 95% confidence interval (95%CI) for outcome events in patients with type 2 diabetes and CAD using Cox proportional hazard models. The comparison between the IP and IS groups was performed using the randomized design of the BARI 2D trial separately for nonobese (n = 1021) and obese (n = 1319) patients. The primary outcome was a composite endpoint including all-cause death, myocardial infarction, and stroke. ResultsDuring the follow-up, 231 nonobese and 295 obese patients had one confirmed primary outcome event. In nonobese patients, the risk of primary outcome events was significantly higher in the IP group than the IS group (HR: 1.30, 95%CI: 1.00–1.68, P = 0.04), whereas that in obese patients did not differ significantly between the two groups. Moreover, in nonobese patients, the risk of primary outcome events in those without abdominal obesity was significantly higher in the IP group than that in the IS group (HR: 1.51, 95%CI: 1.05–2.19, P = 0.02). There were no significant interactions between the strategy for glycemic control and various subgroups of nonobese patients. ConclusionsIn nonobese patients with type 2 diabetes and CAD, the IS treatment strategy may be more beneficial than the IP treatment strategy.

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

BackgroundThe 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. ObjectivesThis 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]). MethodsThe 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. ResultsOf 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. ConclusionsAmong 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.

Thrombotic/Thrombolytic Balance as a Cardiac Treatment Determinant in Patients With Diabetes Mellitus and Coronary Artery Disease.

BackgroundThis study aimed to assess whether the plasminogen activator inhibitor‐1/tissue plasminogen activator (PAI‐1/tPA) ratio as a prothrombotic state is useful for optimizing cardiac treatment strategy.Methods and ResultsUsing BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial data, we used a Cox proportional hazard model to calculate hazard ratios with 95% CIs for cardiac events in patients receiving early revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or medical therapy, separately in patients with low (n=1276) and high (n=894) PAI‐1/tPA ratios. The primary outcome was major cardiac events, which was a composite end point including cardiac death and nonfatal myocardial infarction. The mean±SD follow‐up period was 4.1±1.7 years. The risk of major cardiac events in patients with high PAI‐1/tPA ratio was significantly higher when receiving percutaneous coronary intervention (hazard ratio, 1.84; 95% CI, 1.16–2.93; P=0.01) than when receiving medical therapy, whereas that in patients with low PAI‐1/tPA ratio did not differ significantly between the groups (hazard ratio, 0.95; 95% CI, 0.66–1.36; P=0.77); the interaction between the cardiac treatment strategy and PAI‐1/tPA ratio was significant (P=0.02). However, regardless of the PAI‐1/tPA ratio, major cardiac event risk seemed to be lower in patients receiving coronary artery bypass grafting than in those receiving medical therapy.ConclusionsIn patients with type 2 diabetes mellitus and coronary artery disease, this study demonstrated that those with high PAI‐1/tPA ratio were at higher risks of major cardiac events when treated with percutaneous coronary intervention than when treated with intensive medical therapy.

A genetic locus on chromosome 2q24 predicting peripheral neuropathy risk in type 2 diabetes: Results from the ACCORD and BARI 2D studies

A genetic locus on chromosome 2q24 predicting peripheral neuropathy risk in type 2 diabetes: Results from the ACCORD and BARI 2D studies

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

BackgroundDiabetic medications can cause hypoglycemia, which may lead to myocardial damage. ObjectivesThis study sought to determine whether hypoglycemia is associated with higher levels of high-sensitivity cardiac troponin T (hsTnT). MethodsThe 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. ResultsOf 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. ConclusionsHypoglycemia 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)

Dual antiplatelet therapy versus aspirin monotherapy in diabetics with stable ischemic heart disease undergoing coronary artery bypass grafting.

Dual antiplatelet therapy (DAPT) in patients presenting with acute coronary syndrome (ACS) undergoing CABG is recommended to prevent recurrent ischemic events. The benefit of DAPT post-CABG in patients with stable ischemic heart disease (SIHD) is unknown. The aim of this study was to evaluate the utilization rate of DAPT and associated outcomes in patients with SIHD undergoing CABG via a secondary analysis of Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data. In a post-hoc, nonrandomized analysis from the BARI 2D trial, we compared patients receiving DAPT and aspirin monotherapy within 90 days post-randomization. The primary outcome was the risk adjusted 5-year composite of all-cause mortality, nonfatal myocardial infarction (MI), or stroke. We analyzed patients assigned to prompt CABG treatment arm including both the insulin therapy assignments. Of 378 patients, within 90 days post-randomization, 59 (16%) patients received DAPT and 319 (84%) patients received aspirin alone. Cox proportional hazard analysis demonstrated that there was no significant difference in the 5-year composite event of death, MI, and stroke between DAPT and monotherapy cohorts [13 (22.0%) vs. 61 (19.1%); adjusted hazard ratio (HR): 1.06; 95% confidence interval (CI): 0.56 to 2.00; P=0.86]. There also was no significant difference at 1 year in the composite event [6 (10.2%) vs. 30 (9.4%); HR: 1.13; 95% CI: 0.46 to 2.79; P=0.79]. The use of DAPT in patients with diabetes post-CABG in this cohort was low. Compared with aspirin monotherapy, no associated differences were observed in cardiovascular outcomes. Larger prospective studies are needed to further elucidate this observation.

Cardiovascular Protection in People With Diabetes.

Cardiovascular Protection in People With Diabetes.

Dyslipidemia.

Dyslipidemia.

Thiazolidinediones and Risk of Atrial Fibrillation Among Patients with Diabetes and Coronary Disease

BackgroundWe sought to determine whether insulin-sensitizing therapy (thiazolidinediones or metformin) decreased the risk of developing atrial fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the inflammatory response. Because inflammation is a risk factor for atrial fibrillation, we hypothesized that treating diabetes with thiazolidinediones might decrease the risk of developing atrial fibrillation. MethodsThe Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled patients with type 2 diabetes and documented coronary artery disease. All patients were randomized to insulin-sensitizing therapy or insulin-providing therapy. ResultsA total of 2319 patients entered the study, with 1160 assigned to the insulin-sensitization strategy and 1159 assigned to the insulin-provision strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new-onset atrial fibrillation. In the intention-to-treat analysis, the incidence of atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin sensitization compared with 9.5 in patients assigned to insulin provision with a hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In a time-varying exposure analysis, the incidence rate per 1000 person-years was 7.2 while exposed to thiazolidinediones and 9.7 while not exposed to thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a subset of patients matched on propensity to receive a thiazolidinediones, the HR was 0.75 (95% CI, 0.43-1.30, P = .30). ConclusionsWe did not find a significant reduction of atrial fibrillation incidence with use of thiazolidinediones.