Diabetes atorvastatin

In high-risk individuals and groups people with clinical evidence of macrovascular disease other than CHD, the Heart Protection Study (HPS) (II) with diabetes, the HPS and Collaborative Atorvastatin Diabetes Study (CARDS) (12) the elderly, Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) (13) or with hypertension, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (14) and Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) (15). 

Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) multicentre randomised placebo-controlled trial. Lancet 2004 364 685-696. 

AECAPS/TexCAPS = Air ForceAexas Coronary Atherosclerosis Prevention Study (Downs et ah, 1998) Helsinki = The Helsinki Heart Study (Frick et al., 1 987) LRC-CPPT = The Lipid Research Clinics Coronary Primary Prevention Trial (insull et al., 1984) Oslo = The Oslo Study (Hjermann et ah, 1988) WOSCOPS = The West of Scotland Coronary Prevention Study (Shepherd et al., 1995) ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial approximately 13-15% of patients had a history of coronary heart disease (CHD) events are CHD events only WHI = Women s Health initiative RRR = relative risk reduction ARR = absolute risk reduction NNT = number needed to treat NA = not available CEE = conjugated equine estrogen MPA = medroxyprogesterone acetate CARDS = Collaborative Atorvastatin Diabetes Study (presented at the 2004 American Diabetes Association meeting). 

Support for the findings of HPS came from the Collaborative Atorvastatin Diabetes Study (CARDS) the first end point trial to be performed in a specific diabetic population [50]. Totally, 2,838 type 2 diabetic patients (aged 40-75 years) without clinical CVD but with one other risk factor. 

Currently, there are a number of systemic and intestine-selective MTP inhibitors, including lomitapide (23, BMS-201038, AEGR-733), implitapide (24), JTT-130, SLx-4090, and R-256918 (latter three structures not disclosed) believed to be in active development [60]. In a meta-analysis of three Phase II clinical trials, lomitapide as monotherapy or in combination with ezetimibe, atorvastatin, or fenofibrate significantly reduced LDL cholesterol (up to 35% as monotherapy and 66% in combination with atorvastatin) and was well tolerated with less than 2% discontinuation due to abnormal liver function [61]. Lomitapide has also been granted orphan drug status for the treatment of homozygous familial hypercholesterolemia [59]. Results of a Phase II study of JTT-130 for type 2 diabetes are expected in August 2010 [59,60]. 

A 49-year-old man with pre-existing hepatic pathology took rosiglitazone 4 mg/day for 2 months and 8 mg/day for 5 months (114). He developed a bull face and then edema of the eyelids and neck. He had anorexia and nausea. His serum sodium was 110 mmol/1, potassium 3.3 mmol/1, chloride 81 mmol/1, cholesterol 21 mmol/1, triglycerides 33 mmol/1, and his liver enzymes were raised. Rosiglitazone was withdrawn and he was given saline and potassium, acarbose for his diabetes, spironolactone 200 mg/day for edema, and atorvastatin 10 mg/ day for hyperlipidemia. He improved over 3 weeks. 

Potentially life-threatening toxic epidermal necrolysis occurred in a 73-year-old moderately obese woman with type 2 diabetes and hypertension after she had taken 40 mg of atorvastatin (17). 

When troglitazone was added in four men with diabetes using insulin and taking atorvastatin, serum LDL cholesterol and triglycerides increased by 23 and 21% respectively (118). This suggests a drug interaction, but further studies are warranted to substantiate this. 

The CARDS randomized 2838 people with Type 2 diabetes plus retinopathy, microalbuminuria, hypertension, or smoking and no history of macrovascular disease to receive either ator-vastatin or placebo. Atorvastatin reduced the combined... 

Hypertriglyceridemia usually responds well to niacin, gemfibrozil, or high-dose/potency statins (e.g., atorvastatin or simvastatin) niacin should be used cautiously in diabetics because of worsening glycemic control. 

Knopp RH, d Emden M, Smilde JG, Pocock SJ (2006) Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insuUn-dependent diabetes meUitus (ASPEN), Diabetes Care 29 1478-1485. 

The diabetes subgroup (n = 2532) from the Anglo Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm (ASCOT-LLA) showed a similar trend (test for heterogeneity not significant) to reduction of CVD events as those without diabetes. This nial is of particular interest because the benefits of statin therapy (atorvastatin 10 mg/day) were seen in well-ffeated hypertensive patients [51]. 

Statin trials demonstrated a 21.5 risk reduction for every 1 nunol/L decrease in LDL-cholesterol [52]. This reduction in stroke risk was seen in patients without previous stroke, hi CARDS the reduction in stroke was 48% [50], Recently, the results of the first statin trial to recruit a specific population of stroke or TIA survivors (n = 4731) with time to subsequent stroke as the primary end point has been reported [53], Statin therapy (atorvastatin 80 mg/day) was associated with a reduction in subsequent stroke of 16% (HR 0.84 95% Cl 0.71-0.99, p < 0.03). As might be predicted, secondary end points of major coronary events showed highly significant reductions. The results of the diabetes subgroup have not yet been published. 

However, in a study in healthy subjects, pioglitazone 45 mg daily did not significantly affect the pharmacokinetics of simvastatin 80 mg daily and concurrent use was well tolerated. Similarly, there was no pharmacokinetic interaction between pioglitazone 45 mg daily and atorvastatin 80 mg daily Moreover, clinical use of rosiglitazone with atorvastatin in patients with type 2 diabetes for 16 weeks was well tolerated, as was the clinical use of rosiglitazone or pioglitazone with simvastatin."... 

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