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

Decay index: a new carotid doppler waveform measure associated with the windkessel function of elastic arteries

The Windkessel function of elastic arteries determines the postpeak contour of the internal carotid artery (ICA) Doppler waveform. To introduce an indicator for the function, the postpeak contour was reproduced by an exponential function, and the exponential coefficient was termed "Decay Index" (DI). DI obtained from 108 stenosis-free ICAs (55.2 ± 15.8 y) was compared with surrogate measures for the Windkessel function (aortic pulse wave velocity, pulse pressure) and ICA peripheral resistance (resistive index, pulsatility index, systolic-to-diastolic ratio). DI was moderately correlated with the Windkessel and the resistance measures (r ranged 0.44–0.57). To clarify these intercorrelations, principal component analysis revealed two components. The first was loaded by the resistance measures (component load = 0.93) although the second was loaded by the Windkessel measures and DI (= 0.70), supporting an association between DI and the Windkessel function. Thus, DI is likely to represent an indicator for the Windkessel function

Supplementary Material for: Detection of Atherosclerotic Cardiovascular Disease in Patients with Advanced Chronic Kidney Disease in the Cardiology and Nephrology Communities

<b><i>Background:</i></b> Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality among patients with chronic kidney disease (CKD) with a glomerular filtration rate of < 60 mL/min/1.73 m² body surface area. The availability of high-quality randomized controlled trial data to guide management for the population with CKD and ASCVD is limited. Understanding current practice patterns among providers caring for individuals with CKD and CVD is important in guiding future trial questions. <b><i>Methods:</i></b> A qualitative survey study was performed. An electronic survey regarding the diagnosis and management of CVD in patients with CKD was conducted using a convenience sample of 450 practicing nephrology and cardiology providers. The survey was administered using Qualtrics® (https://www.qualtrics.com). <b><i>Results:</i></b> There were a total of 113 responses, 81 of which were complete responses. More than 90% of the respondents acknowledged the importance of CVD as a cause of morbidity and mortality in patients with CKD. Outside the kidney transplant evaluation setting, 5% of the respondents would screen an asymptomatic patient with advanced CKD for ASCVD. Outside the kidney transplant evaluation scenario, the respondents did not opt for invasive management strategies in advanced CKD. <b><i>Conclusions:</i></b> The survey results reveal a lack of consensus among providers caring for patients with advanced CKD about the management of ASCVD in this setting. Future randomized controlled trials will be needed to better inform the clinical management of ASCVD in these patients. The limitations of the study include its small sample size and the relatively low response rate among the respondents