Statin-fibrate combination therapy for hyperlipidemia: a review

Statins and fibrates are well-established treatments for hyperlipidaemias and the prevention of vascular events. However, fibrate + statin therapy has been restricted following early reports of rhabdomyolysis that mainly involved gemfibrozil, originally with lovastatin, and recently, with cerivastatin. Despite this limitation, several reports describing combination therapy have been published. This review considers these studies and the relevant indications and contraindications. Statin + fibrate therapy should be considered if monotherapy or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids or nicotinic acid) did not achieve lipid targets or is impractical. Combination therapy should be hospital-based and reserved for high-risk patients with a mixed hyperlipidaemia characterised by low density lipoprotein cholesterol (LDL) > 2.6 mmol/l (100 mg/dl), high density lipoprotein cholesterol (HDL) < 1.0 mmol/l (40 mg/dl) and/or triglycerides > 5.6 mmol/l (500 mg/dl). These three 'goals' are individually mentioned in guidelines. Patients should have normal renal, liver and thyroid function tests and should not be receiving therapy with cyclosporine, protease inhibitors or drugs metabolised through cytochrome P450 (especially 3A4). Combination therapy is probably best conducted using drugs with short plasma half-lives; fibrates should be prescribed in the morning and statins at night to minimise peak dose interactions. Both drug classes should be progressively titrated from low doses. Regular (3-monthly) monitoring of liver function and creatine kinase is required. In conclusion, fibrate + statin therapy remains an option in high-risk patients. However, long-term studies involving safety monitoring and vascular endpoints are required to demonstrate the efficacy of this regimen

A Study on the Effect of the Stress State on Ductile Fracture

The main purpose of this paper is to demonstrate that besides the stress triaxiality parameter, the Lode angle, which can be related to the third invariant of the deviatoric stress tensor, also has an important effect on ductile fracture. This is achieved by conducting a series of micromechanics analyses of void-containing unit cells and experimental-numerical studies of carefully designed specimens experiencing a wide range of stress states. As a result, a fracture criterion is expressed in terms of the equivalent failure strain as a function of the stress triaxiality and the Lode angle (or the third invariant of the stress deviator) and this function is calibrated for a DH36 steel plate