Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes

IMPORTANCE: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk. OBJECTIVE: To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Posttrial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study between July 2009 and October 2014; 5 years of follow-up were completed for a total of 9.7 years at general community and academic outpatient research clinics in the United States and Canada. Of the original 5518 ACCORD Lipid Trial participants, 4644 surviving participants were selected based on the presence of type 2 diabetes and either prevalent CVD or CVD risk factors and high-density lipoprotein levels less than 50 mg/dL (<55 mg/dL for women and African American individuals). INTERVENTIONS: Passive follow-up of study participants previously treated with fenofibrate or masked placebo. MAIN OUTCOMES AND MEASURES: Occurrence of cardiovascular outcomes including primary composite outcome of fatal and nonfatal myocardial infarction and stroke in all participants and in prespecified subgroups. RESULTS: The 4644 follow-on study participants were broadly representative of the original ACCORD study population and included significant numbers of women (n = 1445; 31%), nonwhite individuals (n = 1094; 21%), and those with preexisting cardiovascular events (n = 1620; 35%). Only 4.3% of study participants continued treatment with fenofibrate following completion of ACCORD. High-density lipoprotein and triglyceride values rapidly equalized among participants originally randomized to fenofibrate or placebo. Over a median total postrandomization follow-up of 9.7 years, the hazard ratio (HR) for the primary study outcome among participants originally randomized to fenofibrate vs placebo (HR, 0.93; 95% CI, 0.83-1.05; P = .25) was comparable with that originally observed in ACCORD (HR, 0.92; 95% CI, 0.79-1,08; P = .32). Despite these overall neutral results, we continued to find evidence that fenofibrate therapy effectively reduced CVD in study participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL and high-density lipoprotein cholesterol levels less than 34 mg/dL (HR, 0.73; 95% CI, 0.56-0.95). CONCLUSIONS AND RELEVANCE: Extended follow-up of ACCORD-lipid trial participants confirms the original neutral effect of fenofibrate in the overall study cohort. The continued observation of heterogeneity of treatment response by baseline lipids suggests that fenofibrate therapy may reduce CVD in patients with diabetes with hypertriglyceridemia and low high-density lipoprotein cholesterol. A definitive trial of fibrate therapy in this patient population is needed to confirm these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000620

Effect of the frequency on the gas sensing response of CoSb2O6 prepared by a colloidal method

Background: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear. Objective: To examine the long-term renal effects of telmisartan versus placebo in adults at high vascular risk. Design: Randomized trial. Patients were randomly assigned by a central automated system between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status. Setting: Multicenter, multinational study. Patients: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. Intervention: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months. Measurements: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Results: No important difference was found in the composite renal outcome with telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P = 0.001). Decreases in estimated GFR were greater with telmisartan than with placebo (mean change in estimated GFR, -3.2 mL/min per 1.73 m2 [SD, 18.3] vs. -0.26 mL/min per 1.73 m2 [SD, 18.0]; P &lt; 0.001). Limitation: Only 17 participants had dialysis. Conclusion: In adults with vascular disease but without macroalbuminuria, the effects of telmisartan on major renal outcomes were similar to those of placebo. Primary Funding Source: Boehringer Ingelheim. " 2009 American College of Physicians.",,,,,,,,,"http://hdl.handle.net/20.500.12104/41020","http://www.scopus.com/inward/record.url?eid=2-s2.0-67650070753&partnerID=40&md5=65c169e732d05dd4c701e39f67193548",,,,,,"1",,"Annals of Internal Medicine",,"

Effect of telmisartan on renal outcomes: A randomized trial

Background: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear. Objective: To examine the long-term renal effects of telmisartan versus placebo in adults at high vascular risk. Design: Randomized trial. Patients were randomly assigned by a central automated system between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status. Setting: Multicenter, multinational study. Patients: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. Intervention: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months. Measurements: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. Results: No important difference was found in the composite renal outcome with telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P = 0.001). Decreases in estimated GFR were greater with telmisartan than with placebo (mean change in estimated GFR, -3.2 mL/min per 1.73 m2 [SD, 18.3] vs. -0.26 mL/min per 1.73 m2 [SD, 18.0]; P &lt; 0.001). Limitation: Only 17 participants had dialysis. Conclusion: In adults with vascular disease but without macroalbuminuria, the effects of telmisartan on major renal outcomes were similar to those of placebo. Primary Funding Source: Boehringer Ingelheim. © 2009 American College of Physicians

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

Background: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagonlike peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. Methods: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallelgroup, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Results: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m2, and duration of T2DM was 9.3±8.2 years. The qualifying ACS wasamyocardial infarctionin83% and unstableangina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. Conclusion: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk. © 2015 Elsevier Inc. All rights reserved