Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: An open-label, multicenter study

Aguilar-Salinas, Carlos A.; n, Guillermo Fangh; Meza, Edilberto; Montes, J. López; as-Herrero, Alfonso Gul; nchez, Leticia S; Monterrubio‐Flores, Eric; lez-Valdez, H; rez, Francisco J. G

doi:10.1053/meta.2001.23308

Cited by 23 publications

(6 citation statements)

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“…38,39 Fibrates also decrease levels of plasminogen activator inhibitor 1 and-in contrast to statins-certain fibrates also decrease plasma fibrinogen concentrations. 40,41 Multifaceted actions in type 2 diabetes mellitus Investigations suggest PPARα is implicated in the development of microvascular complications associated with diabetes. PPARα agonists could, therefore, counteract diabetic nephropathy.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Fibrates and future PPARα agonists in the treatment of cardiovascular disease

2008

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Statins lower cardiovascular risk in patients with diabetes; however, as these patients are at higher risk than other cardiovascular patients, statins merely decrease coronary event rates to the level seen in untreated nondiabetic individuals at risk for cardiovascular disease, indicating the existence of substantial residual risk. One reasonable explanation resides in the fact that statins have only limited effectiveness on hypertriglyceridemia and low HDL cholesterol, and they do not normalize the LDL size-distribution pattern. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include fibrates, normalize this atherogenic lipid profile, as well as several cardiovascular risk markers associated with the metabolic syndrome and type 2 diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large buoyant LDL particles are significantly improved. Outcome trials of PPARalpha agonists have demonstrated reductions in cardiovascular morbidity in patients with diabetes and in those with the metabolic syndrome; plaque progression is diminished, diabetic nephropathy and retinopathy are counteracted and amputation-risk decreased. The combination of fibrates with statins improves overall lipoprotein profile further. PPARalpha agonists seem particularly indicated in patients with diabetes who have residual dyslipidemia (high triglyceride and/or low HDL) despite receiving statin therapy, and patients who are nondiabetic, overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL cholesterol and chronic inflammation.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

Fibrates and future PPARα agonists in the treatment of cardiovascular disease

2008

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“…The abundance of desirable effects of PPAR-alpha activation by fibrates has generated extraordinary interest in their role in the prevention of atherosclerosis via regulation of lipid metabolism, vascular inflammation, and haemostatic factors. The importance of changes in apolipoprotein B and non-HDL-cholesterol levels appears greater with fibrate therapy than with statin use [36], particularly in patients with type 2 diabetes [37]. Increased interest in the FIELD study has resulted, as it will generate clinical data on similar numbers of persons with diabetes to that available for the statins (Table 4) and will enlarge the range of lipid profiles studied and the number of events in such populations (Table 5).…”

Section: Resultsmentioning

confidence: 99%

The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]

Barter

Best

Colman

et al. 2004

Cardiovasc Diabetol

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Background: Fibrates correct the typical lipid abnormalities of type 2 diabetes mellitus, yet no study, to date, has specifically set out to evaluate the role of fibrate therapy in preventing cardiovascular events in this setting. Methods:Subjects with type 2 diabetes, aged 50-75 years, were screened for eligibility to participate in a long-term trial of comicronized fenofibrate 200 mg daily compared with matching placebo to assess benefits of treatment on the occurrence of coronary and other vascular events. People with total cholesterol levels 3.0-6.5 mmol/L plus either a total-to-HDLc ratio >4.0 or triglyceride level >1.0 mmol/L with no clear indication for lipid-modifying therapy were eligible.Results: A total of 9795 people were randomized into the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All received dietary advice, followed by a 6-week single-blind placebo run-in, then a 6-week active run-in period before randomization. Participants are being followed up every 6 months for outcome events and safety assessments. The study is designed to yield at least 500 coronary events (primary endpoint: first nonfatal myocardial infarction or coronary death) over 5 years, to have 80% power to identify as statistically significant at 2P = 0.05 a 22% reduction in such events, using intention-to-treat methods. Conclusions:Type 2 diabetes is the most common endocrine disorder worldwide, and its prevalence is increasing. The current evidence about use of fibrates in type 2 diabetes, from around 2000 people treated, will increase with FIELD to evidence from around 12000. FIELD will establish the role of fenofibrate treatment in reducing cardiovascular risk in people with type 2 diabetes. The main results are expected to be available in late 2005.

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“…In this study, we found that the triglyceride concentration was decreased by 17.8% after 100 mg day −1 ciprofibrate treatment. Other authors have reported a reduction of 43.5% in triglyceride concentration in dyslipidaemic patients after 8 weeks of therapy [30]. Blane et al.…”

Section: Discussionmentioning

confidence: 99%

Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome

Paragh

Serés

Harangi

et al. 2006

Brit J Clinical Pharma

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Aims Diabetic dyslipidaemia with decreased high‐density lipoprotein‐cholesterol (HDL‐C) concentration plays a key role in enhanced atherosclerosis. The antioxidant effect of HDL is due to the influence of human paraoxonase 1 (PON1) and several authors have described decreased activity of this enzyme in Type 2 diabetics and subjects with metabolic syndrome. The goal of this study was to examine the effect of daily ciprofibrate on serum PON1 and lipoprotein concentrations in patients with metabolic syndrome. Methods Fifty‐one patients with metabolic syndrome were enrolled into the study. We examined the effect of 100 mg day−1 ciprofibrate treatment on lipid concentrations, oxidized low‐density lipoprotein (LDL), PON1 concentrations and activity. We also investigated the calculated size of LDL‐cholesterol (LDL‐C). Results During the 3‐month study, it was observed that following treatment with ciprofibrate, the serum triglyceride concentration decreased significantly (from 2.76 ± 0.9 mmol l−1 to 2.27 ± 1.6 mmol l−1; −18%; P < 0.001), while HDL‐C increased significantly (from 0.95 ± 0.2 mmol l−1 to 1.2 ± 0.3 mmol l−1; 26%; P < 0.001). The oxidatively modified LDL‐C concentration decreased significantly (from 137 ± 19 U l−1 to 117 ± 20 U l−1; P < 0.001), while HDL‐associated apolipoprotein A1 significantly increased (from 1.35 ± 0.2 g l−1 to 1.75 ± 0.3 g l−1; P < 0.001). The LDL‐C/LDL‐apoB ratio, which reflects the size of LDL, increased significantly (from 0.96 ± 0.05 to 1.05 ± 0.06; P < 0.05). Serum PON1 activity was significantly elevated (from 108 ± 34 U l−1 to 129 ± 31 U l−1; P < 0.05), while standardized values for HDL‐C remained significantly unchanged (PON1/HDL‐C) (from 114 ± 21 to 107 ± 20; NS). Conclusion Three months of treatment with ciprofibrate favourably affected the lipid profile, increased LDL resistance to oxidation and improved antioxidant status by increasing serum paraoxonase activity in these patients.

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Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: An open-label, multicenter study

Cited by 23 publications

References 0 publications

Fibrates and future PPARα agonists in the treatment of cardiovascular disease

Fibrates and future PPARα agonists in the treatment of cardiovascular disease

The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]

Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome

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