Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study).

Diabetes mellitus is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia. Besides acting on traditional lipids, statins and fibrates may also exert beneficial effects on various pro- and antiatherogenic lipid subparticles. This analysis was undertaken to evaluate combination therapy on lipid subparticles in the Diabetes and Combined Lipid Therapy Regimen (DIACOR) study. Patients with type 2 diabetes mellitus and no histories of coronary heart disease were evaluated (n = 498). Eligible patients underwent a 6- to 8-week washout period of all lipid-lowering medications and were enrolled if they demonstrated mixed dyslipidemia (having >or=2 of the following 3 lipid parameters: low-density lipoprotein [LDL] cholesterol >or=100 mg/dl, triglycerides >or=200 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl). Patients were randomized to simvastatin 20 mg, fenofibrate 160 mg, or combined simvastatin 20 mg and fenofibrate 160 mg. Lipid subparticles were assessed 12 weeks after randomization by the Vertical Auto Profile II method. A total of 300 patients (mean age 61.6 +/- 11.5 years, 55% men) were randomized. Combination therapy was superior in lowering LDL cholesterol pattern B (-33.9 mg/dl) and dense very low-density lipoprotein cholesterol (-10.0 mg/dl) and increasing high-density lipoprotein3 (+2.3 mg/dl) and exerted the greatest change in altering the LDL cholesterol size profile. A potential effect on lipoprotein(a) (-0.5 mg/dl) was also found. For those with triglycerides >170 mg/dl, combination therapy was superior in lowering dense very low density lipoprotein cholesterol (-10.7 mg/dl) and LDL cholesterol pattern B (-35.8 mg/dl), the lipids that tend to be formed in the presence of elevated triglycerides. In conclusion, in this trial of mixed dyslipidemic patients with diabetes, combination therapy was more effective in changing a variety of other cardiovascular risk markers.

The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.

OBJECTIVES: The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes. BACKGROUND: Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes. METHODS: Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)). RESULTS: At 12 weeks, median hsCRP was significantly reduced (-14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = -18.9%, p = 0.002 vs. baseline; simvastatin = -24.8%, p < 0.0001; combination = -27.3%, p = 0.002). Likewise, median Lp-PLA(2) levels in the overall study population were significantly reduced (-16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA(2) greater than the median of 320.9 ng/ml (fenofibrate = -41.3%, p < 0.0001; simvastatin = -47.5%, p < 0.0001; combination = -46.8%, p < 0.0001). CONCLUSIONS: Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA(2). These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1).

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain. METHODS: The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG > or =126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 +/- 1.2 years. RESULTS: The average patient age was 62 +/- 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM, 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P =.04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG > or =109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P =.002) remained independent predictors of mortality. CONCLUSIONS: Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.

Preoperative use of enoxaparin compared with unfractionated heparin increases the incidence of re-exploration for postoperative bleeding after open-heart surgery in patients who present with an acute coronary syndrome: clinical investigation and reports.

BACKGROUND: Enoxaparin has become an attractive therapy for use during acute coronary syndrome (ACS) because of its potential superior efficacy over unfractionated heparin (UFH), its longer activity, and its subcutaneous route of administration. However, because a significant number of patients presenting with ACS may be sent directly to open heart surgery while still on anticoagulation, it is important to understand any potential bleeding risks that may be associated with the use of enoxaparin under these circumstances. METHODS: From 1998 to 2001, 1159 consecutive patients presenting with an acute coronary syndrome who received either UFH (n=1008) or enoxaparin (n=151) before proceeding to open heart surgery for urgent therapy during the same hospitalization were included in this study. Incidence of perioperative bleeding as evidenced by the units of blood products (packed red blood cells or platelets) transfused or the need for surgical re-exploration for postoperative bleeding was recorded. RESULTS: Average age was 65+/-11 and 67+/-11 years for patients receiving UFH and enoxaparin, respectively (P=0.005). Seventy-five percent of those receiving UFH and 64% of those receiving enoxaparin (P<0.005) were males. After discharge, the incidence of rehospitalization for hemorrhage requiring return to surgery for re-exploration was 7.9% in the enoxaparin group and 3.7% in the UFH group (adjusted hazard ratio=2.6, P=0.03). The use of blood products did not differ between groups (UFH=2.7+/-6.5 U and enoxaparin=2.3+/-4.5 U; P=NS). CONCLUSION: The preoperative use of enoxaparin compared with UFH in patients presenting with an ACS who undergo open-heart surgery during the same hospitalization is associated with a significantly increased incidence of re-exploration for postoperative bleeding. Further study is needed to understand the mechanism of this phenomenon and to develop appropriate guidelines to address this potentially important issue.