Dyslipidemia
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
Lifestyle changes and statins are always involved in the reduction of LDL to treat diabetic dyslipidemia. Fibrates can decrease TGs and reduce risks for pancreatitis. Metformin reduces total triglycerides and may be preferred over other oral antihyperglycemic for diabetes. Certain thiazolidinediones (TZDs) increase HDL as well as LDL, and some also decrease total triglycerides – meaning they are not preferred for lipid abnormalities in diabetic patients but can be useful adjunctive medications. Those with very high total triglycerides and poorly controlled diabetes may respond better to insulin than oral antihyperglycemics. With dyslipidemia, underlying disorder such as chronic kidney disease, hypothyroidism, or liver disease must be treated first. In patients with low to normal thyroid function, hormone replacement may improve abnormal lipid levels. If any drugs are causing lipid abnormalities, they should be reduced or stopped.
Disorders of lipid metabolism
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Fibrates are generally well tolerated. However, they have important interactions with other drugs that are of particular relevance in the elderly. Due to increased risk of myopathy in combination with statins, fibrates should be used in this setting with only the utmost caution, and probably avoided in those with risk factors for myopathy. An interaction of warfarin with fibrates leads to an increase in warfarin levels and the international normalized ratio. Thus, warfarin is typically dosed at one third its standard dose when administered with fenofibrate and careful follow-up of the international normalized ratio is needed. Given fibric acid derivatives are excreted primarily through the kidney, if they are used in the setting of chronic kidney disease, then dose adjustment is necessary. Gastrointestinal side effects are common in patients taking fibrate therapy, including mild nausea during the first week of therapy. To reduce this potential side effect, it can be useful to start treatment with one half the normal dose for several days before increasing to a full dose.
Metabolic Syndrome and Cardiovascular Disease: Epidemiology, Pathophysiology, and Therapeutic Considerations
P. K. Shah in Risk Factors in Coronary Artery Disease, 2006
The agonistic mechanism of actions of the fibric acid derivates (gemfibrozil, clofibrate, fenofibrate) on PPARα was described above in approaches to insulin resistance. The firbrates are considered the most effective triglyceride-lowering drugs, producing as much as 50% reduction. Clofibrate and fenofibrate cause fewer gastrointestinal symptoms than gemfibrozil. Clofibrate can cause erectile dysfunction. Currently fenofibrate is the preferred agent. All fibrates are renally excreted and can accumulate in the serum in patients with renal failure and lead to myositis. Ezetimibe is the first of a new class of lipid-lowering drugs known as intestinal cholesterol absorption inhibitors. It could be administered in once daily doses of 10 mg. The co-administration of ezetimibe with statins offers a well-tolerated and efficacious treatment of lower LDL-C in patients with metabolic syndrome and diabetes (89). The combination of statin and ezetimibe and statin may result in a small increase in the incidence of elevated liver enzyme levels, although cases of severe hepatotoxicity have not been demonstrated (90).
Kidney and lipids: novel potential therapeutic targets for dyslipidemia in kidney disease?
Published in Expert Opinion on Therapeutic Targets, 2022
Konrad Zuzda, Wiktoria Grycuk, Jacek Małyszko, Jolanta Małyszko
Fibrates lower triglyceride levels by up to 50%, reduce LDL, and increase HDL-C by 5–20% [150,151]. They raise HDL up to 20% in patients with very high triglyceride levels (>500 mg/dL [5.7 mmol/L]), whereas a rise up to 5% is seen in individuals with lower triglyceride levels on fibrate monotherapy. However, the available data do not support the routine use of fibrates as add-on drugs to statin [152]. Data on fibrate use in patients with CKD or on dialysis are limited. Magid et al. [153] studied the safety and efficacy of either fenofibrate 100 mg or simvastatin 20 mg administered for 16 weeks on the lipid profile, oxidized low-density lipoprotein (Ox-LDL), glutathione peroxidase, and C-reactive protein in 60 dialyzed patients. They found that both drugs lowered cholesterol, triglycerides, low-density lipoprotein (LDL), and ox-LDL levels (p < 0.05) and had no effect on C-reactive protein levels. They concluded that both drugs were well tolerated with no serious adverse events.
Safety and efficacy of therapies for chylomicronemia
Published in Expert Review of Clinical Pharmacology, 2022
Isabel Shamsudeen, Robert A. Hegele
Fibrates are activators of peroxisome proliferator-activated receptors (PPARs), particularly the alpha isoform; their multiple effects include suppression of hepatic apo C-III production, which reduces the production of hepatic VLDL and disinhibits LPL activity [39]. Fibrates can reduce TG levels by up to 50% in patients with a functional lipolytic pathway [40], and via clinical experience are proven to be useful in patients with severe HTG due to MCS. However, in FCS patients with essentially no LPL activity, the response to fibrates is minimal [1]. Available fibrates include gemfibrozil, fenofibrate, bezafibrate, and pemafibrate. The effect of fibrates on ASCVD reduction in statin-treated patients is currently unclear; there have been post-hoc analyses in fibrate trials suggesting ASCVD risk reduction in patients with HTG [41]. The PROMINENT trial is the only study to specifically test this hypothesis, but the study was terminated early due to futility and results have not yet been published [42]. Fibrates are still considered to have value in MCS patients with severe HTG where the clinical concern is acute pancreatitis, and possibly to treat nonalcoholic fatty liver disease.
Targeting triglycerides to lower residual cardiovascular risk
Published in Expert Review of Cardiovascular Therapy, 2022
Kristen J. Bubb, Adam J. Nelson, Stephen J. Nicholls
Fibric acid derivatives are modest agonists of peroxisome proliferator activated receptor-α (PPAR-α) with the ability to lower triglyceride levels by up to 25%, in addition to mild effects on LDL-C and HDL-C levels [29]. Fibrates decrease expression of apoC3, an inhibitor of lipoprotein lipase, and direct upregulation of both lipoprotein lipase and fatty acid oxidation, leading to reduced hepatic lipogenesis [29]. Early clinical trials with gemfibrozil have demonstrated reductions in cardiovascular risk in both the primary and secondary prevention setting [30,31]. Subsequent studies with fenofibrate, conducted with greater background use of statin therapy, failed to demonstrate cardiovascular benefit [32,33]. Meta-analyses of fibrate trials demonstrated that the cardiovascular benefit of fibrates appears to be greatest in the patient with baseline hypertriglyceridemia, identifying the patients most likely to benefit from their use [34].
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