-
1.
A consensus statement on lipid management after acute coronary syndrome.
Schiele, F, Farnier, M, Krempf, M, Bruckert, E, Ferrières, J, ,
European heart journal. Acute cardiovascular care. 2018;(6):532-543
Abstract
In patients admitted for acute coronary syndrome (ACS), the guidelines of the European Society of Cardiology give a Class I, Level A recommendation for the prescription of high-intensity statins to be initiated as early as possible, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Although statins are widely prescribed after ACS, the intensity of therapy and the proportion of patients achieving target LDL-C values are often not in line with recommendations due to a lack of compliance with guidelines by the physicians, a lack of compliance with treatment or poor tolerance by patients, and poor dose adaptation. In this context, a group of French physicians came together to define strategies to facilitate and improve the management of lipid-lowering therapy after ACS. This paper outlines the scientific rationale for the use of statins at the acute phase of ACS, the utility of ezetimibe, the measurement of LDL-C during the course of ACS, the opportunities for detecting familial hypercholesterolaemia and the results of the consensus for the management of lipid-lowering therapy, illustrated in two decision-making algorithms.
-
2.
Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease.
De Luca, L, Arca, M, Temporelli, PL, Colivicchi, F, Gonzini, L, Lucci, D, Bosco, B, Callerame, M, Lettica, GV, Di Lenarda, A, et al
Clinical cardiology. 2018;(8):1075-1083
Abstract
INTRODUCTION Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies.
-
3.
Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels: A Multicenter, Placebo-Controlled, Double-Blind, Randomized Trial.
Arai, H, Yamashita, S, Yokote, K, Araki, E, Suganami, H, Ishibashi, S, ,
Journal of atherosclerosis and thrombosis. 2018;(6):521-538
-
-
Free full text
-
Abstract
AIM: To verify the superiority of pemafibrate over placebo and the non-inferiority of pemafibrate to the maximum dose of fenofibrate for determining the percent change in fasting serum triglyceride (TG) levels and to investigate safety by assessing the incidence of adverse events (AEs) and adverse drug reactions (ADRs). METHODS This phase III, placebo/active drug-controlled, randomized, double-blind, parallel group comparison study enrolled patients with high TG and low high-density lipoprotein cholesterol levels. Patients were randomly assigned to receive placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, or 0.4 mg/day; or fenofibrate 100 mg/day or 200 mg/day for 12 weeks. RESULTS Among 526 randomized patients, 489 completed the study, with drop-out rates of 0%, 6.7%, 5.5%, 5.9%, 8.2%, and 10.7% in the placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, and 0.4 mg/day; and fenofibrate 100 mg/day and 200 mg/day groups. The study showed the non-inferiority of pemafibrate 0.4 mg/day and 0.2 mg/day to fenofibrate 200 mg/day as well the non-inferiority and superiority of all pemafibrate doses to fenofibrate 100 mg/day for reducing TG levels. No dose-dependent increase in the incidence of AEs or ADRs was observed among the pemafibrate dose groups. The incidence of AEs and ADRs for all pemafibrate doses was similar to that for placebo and fenofibrate 100 mg/day and significantly lower than that for fenofibrate 200 mg/day (P<0.05). CONCLUSIONS The favorable safety profile of pemafibrate, with fewer adverse effects on kidney/liver-related laboratory tests and fewer AEs/ADRs, including those leading to treatment discontinuation, over fenofibrate 200 mg/day may justify the use of this novel and potent treatment option for reducing TG levels in a broader range of patients.
-
4.
Lipid-lowering agent-triggered dermatomyositis and polymyositis: a case series and literature review.
Borges, IBP, Silva, MG, Misse, RG, Shinjo, SK
Rheumatology international. 2018;(2):293-301
Abstract
Lipid-lowering agent-triggered dermatomyositis (DM) or polymyositis (PM) is a rare event. Therefore, the aim of the present study was to describe a series of such cases. A retrospective cohort study of 5 DM and 4 PM cases triggered by prior exposure to lipid-lowering agents between 2001 and 2017 was carried out. All patients, except for two cases, had muscle biopsy compatible with inflammatory myopathy and no serum autoantibodies positive for anti-SRP or anti-HMGCoAR. Median age of the patients at time of diagnosis was 68 years. Seven patients had previously taken simvastatin 20 mg/day (exposure period from 2 days to 4 years) and two bezafibrate 100 mg/day (3-4 months). Median time from symptom onset to disease diagnosis was 6 months. All patients with DM had a heliotrope and/or Gottron's papules. All patients had symmetrical, predominantly proximal muscle weakness of limbs, with median serum creatine phosphokinase of 3087U/L (interquartile 25-75% range 1293-13,937 U/L). All patients received glucocorticoid and immunosuppressants. Complete reversal of clinical symptoms and normalization of serum creatine phosphokinase level occurred within a median of 12 months after starting the treatment. There was disease relapse in three cases, and one case of death was unrelated to the disease (pulmonary infectious complications resulting from lymphoma). In contrast to cases described in the literature, the patients in the present study had a relatively more aggressive course, requiring glucocorticoids and immunosuppressants, in addition to a tendency for a longer period to achieve disease remission.
-
5.
Predicting the Effect of Fenofibrate on Cardiovascular Risk for Individual Patients With Type 2 Diabetes.
Koopal, C, Visseren, FLJ, Westerink, J, van der Graaf, Y, Ginsberg, HN, Keech, AC
Diabetes care. 2018;(6):1244-1250
Abstract
OBJECTIVE In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patients who respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to estimate the expected treatment effect of fenofibrate for individual patients with T2DM. RESEARCH DESIGN AND METHODS To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk reduction (ARR), is the difference between treated and untreated MCVE risk. Results were stratified for patients with and without dyslipidemia (i.e., high triglycerides and low LDL cholesterol). RESULTS External validation of the FIELD risk model showed good calibration and moderate discrimination in ACCORD (C-statistic 0.67 [95% CI 0.65-0.69]) and SMART (C-statistic 0.66 [95% CI 0.63-0.69]). Median 5-year MCVE risk in all three studies combined was 6.7% (interquartile range [IQR] 4.0-11.7) in patients without (N = 13,224) and 9.4% (IQR 5.4-16.1%) in patients with (N = 3,918) dyslipidemia. The median ARR was 2.15% (IQR 1.23-3.68) in patients with dyslipidemia, corresponding with a number needed to treat (NNT) of 47, and 0.22% (IQR 0.13-0.38) in patients without dyslipidemia (NNT 455). CONCLUSIONS In individual patients with T2DM, there is a wide range of absolute treatment effect of fenofibrate, and overall the fenofibrate treatment effect was larger in patients with dyslipidemia. The method of individualized treatment effect prediction of fenofibrate on MCVE risk reduction in T2DM can be used to guide clinical decision making.
-
6.
Management of High and Very High-Risk Subjects with Familial Hypercholesterolemia: Results from an Observational Study in Bulgaria.
Petrov, IS, Postadzhiyan, AS, Tokmakova, MP, Kitova, LG, Tsonev, SN, Addison, J, Petkova, RT, Lachev, VI
Folia medica. 2018;(3):389-396
Abstract
BACKGROUND Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period. MATERIALS AND METHODS Twelve cardiology sites participated in this study from May 2015 to May 2016. Eligible subjects had at least two routine low-density lipo-protein cholesterol (LDL C) measurements and a prescription for lipid-lowering therapy (LLT) at the start of the observation period. Mean values for gender, age and cardiovascular (CV) event history at baseline and LDL-C over time were estimated. RESULTS Of the 220 eligible subjects, 196 fulfilled the criteria for FH diagnosis: 27 definite, 94 probable and 75 possible. Mean age at enrolment was 54.4 years and 64.1% of subjects were male. Mean CV risk classification at baseline was 26.8% high-risk (HR) and 73.2% very high-risk (VHR). Mean LDL-C was 5.6 mmol/L at enrolment and 4.1 mmol/L at last observation visit (12 months). The ESC/EAS Guideline LDL-C targets (applicable at the time of the study) were achieved by 14.5% of HR and 5.0% of VHR subjects. Most subjects (n=219) received statins. One subject was statin intolerant (ezetimibe therapy). Intensive statin treatment (atorvastatin 40-80 mg/daily and rosuvastatin 20-40 mg/daily) was used in 38.6% of individuals during the observation period and 10% of subjects received combination therapy (statin plus ezetimibe or other LLT). CONCLUSIONS Most subjects with FH do not reach the ESC/EAS defined LDL-C targets. Early identification and physician education may improve FH management.
-
7.
Fenofibrate for Diabetic Retinopathy.
Stewart, S, Lois, N
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018;(6):422-426
-
-
Free full text
-
Abstract
Fenofibrate is a safe and inexpensive orally administered fibric acid derivative conventionally used to treat dyslipidemia. Two large randomized clinical trials, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies, demonstrated the benefit of oral fenofibrate in the treatment of patients with type 2 diabetes and diabetic retinopathy (DR), including reduced disease progression and need for laser treatment for diabetic macular edema and proliferative diabetic retinopathy. These findings are supported by results of experimental studies, which have demonstrated beneficial effects of fenofibrate ameliorating retinal vascular leakage and leukostasis, downregulating vascular endothelial growth factor, and reducing endothelial cell and pericyte loss, among others; all of these are characteristic features of DR. In spite of this evidence, fenofibrate is not prescribed routinely for treating patients with diabetes and DR. In FIELD and ACCORD studies, retinopathy was not the primary outcome and this may explain, at least partly, its lack of use for this indication. New trials are now underway to specifically address the effects of fenofibrate in DR; these trials will provide additional and robust data that may support current evidence favoring the use of fenofibrate in this common microvascular complication of diabetes.
-
8.
Visit-to-visit lipid variability: Clinical significance, effects of lipid-lowering treatment, and (pharmaco) genetics.
Smit, RAJ, Jukema, JW, Postmus, I, Ford, I, Slagboom, PE, Heijmans, BT, Le Cessie, S, Trompet, S
Journal of clinical lipidology. 2018;(2):266-276.e3
Abstract
In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial. While we identified suggestive associations (P < 1 × 10-6) at 3 different loci (KIAA0391, amiloride-sensitive cation channel 1 neuronal [ACCN1], and Dickkopf WNT signaling pathway inhibitor 3 [DKK3]), previously published data from the genome-wide association study literature did not suggest plausible mechanistic pathways. Given the large degree of both clinical and methodological heterogeneity in the literature, additional research is needed to harmonize visit-to-visit variability parameters across studies and to definitively assess the possible role of (pharmaco)genetic factors.
-
9.
Clinical Inquiries: Does niacin decrease cardiovascular morbidity and mortality in CVD patients?
Lazzopina, P, Mounsey, A, Handler, L
The Journal of family practice. 2018;(5):314-316
Abstract
No. Niacin doesn't reduce cardiovascular disease (CVD) morbidity or mortality in patients with established disease (strength of recommendation [SOR]: A, meta-analyses of randomized controlled trials [RCTs] and subsequent large RCTs). Niacin may be considered as monotherapy for patients intolerant of statins (SOR: B, one well-done RCT).
-
10.
A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption.
Back, HM, Song, B, Pradhan, S, Chae, JW, Han, N, Kang, W, Chang, MJ, Zheng, J, Kwon, KI, Karlsson, MO, et al
BMC pharmacology & toxicology. 2018;(1):4
Abstract
BACKGROUND Oral administration of drugs is convenient and shows good compliance but it can be affected by many factors in the gastrointestinal (GI) system. Consumption of food is one of the major factors affecting the GI system and consequently the absorption of drugs. The aim of this study was to develop a mechanistic GI absorption model for explaining the effect of food on fenofibrate pharmacokinetics (PK), focusing on the food type and calorie content. METHODS Clinical data from a fenofibrate PK study involving three different conditions (fasting, standard meals and high-fat meals) were used. The model was developed by nonlinear mixed effect modeling method. Both linear and nonlinear effects were evaluated to explain the impact of food intake on drug absorption. Similarly, to explain changes in gastric emptying time for the drug due to food effects was evaluated. RESULTS The gastric emptying rate increased by 61.7% during the first 6.94 h after food consumption. Increased calories in the duodenum increased the absorption rate constant of the drug in fed conditions (standard meal = 16.5%, high-fat meal = 21.8%) compared with fasted condition. The final model displayed good prediction power and precision. CONCLUSIONS A mechanistic GI absorption model for quantitatively evaluating the effects of food on fenofibrate absorption was successfully developed, and acceptable parameters were obtained. The mechanism-based PK model of fenofibrate can quantify the effects of food on drug absorption by food type and calorie content.