Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia.

OBJECTIVE: This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile, in comparison to each drug alone, in patients with type 2 diabetes and combined hyperlipidemia (CHL). RESEARCH DESIGN AND METHODS: A total of 120 consecutive patients, who were free of coronary artery disease (CAD) at entry, were studied for a period of 24 weeks. These patients were randomly assigned to atorvastatin (20 mg/day, n = 40), micronized fenofibrate (200 mg/day, n = 40), or a combination of both (atorvastatin 20 mg/day plus fenofibrate 200 mg/day, n = 40). The effect of treatment on LDL cholesterol, triglycerides (TGs), HDL cholesterol, apolipoprotein A-I and B, lipoprotein(a), and plasma fibrinogen (PF) was recorded. Moreover, the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated. RESULTS: No patient was withdrawn from the study because of side effects. The atorvastatin-fenofibrate combination reduced total cholesterol by 37%, LDL cholesterol by 46%, TGs by 50%, and PF by 20%, whereas it increased HDL cholesterol by 22% (P < 0.0001 for all). These changes were significantly better than those of both monotherapies. Of the patients on drug combination, 97.5% reached the LDL cholesterol treatment goal of <100 mg/dl, 100% reached the desirable TG levels of <200 mg/dl, and 60% reached the optimal HDL cholesterol levels of >45 mg/dl. These rates were significantly higher than those of both monotherapies. Combined treatment reduced the 10-year probability for myocardial infarction from 21.6 to 4.2%. CONCLUSIONS: The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL. It improved patients' CAD risk status significantly more than each drug alone.

Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.

BACKGROUND: Atorvastatin is very effective in reducing plasma low-density lipoprotein cholesterol (LDL-C) levels. However, there is no long-term survival study that evaluated this statin. PATIENTS-METHODS: To assess the effect of atorvastatin on morbidity and mortality (total and coronary) of patients with established coronary heart disease (CHD), 1600 consecutive patients were randomised either to atorvastatin or to 'usual' medical care. The dose of atorvastatin was titrated from 10 to 80 mg/day, in order to reach the National Cholesterol Education Program (NCEP) goal of LDL-C <100 mg/dl (2.6 mmol/l). All patients were followed up for a mean period of 3 years. MAIN OUTCOME MEASURES: Primary endpoints of the study were defined as death, non-fatal myocardial infarction, unstable angina, congestive heart failure, revascularisation (coronary morbidity) and stroke. Secondary endpoints were the safety and efficacy of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin. RESULTS: The mean dosage of atorvastatin was 24 mg/day. This statin reduced total chlesterol by 36%, LDL-C by 46%, triglycerides by 31%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 44%, while it increased HDL-C by 7%; all these changes were significant. The NCEP LDL-C and non-HDL-C treatment goals were reached by 95% (n = 759) and 97% (n = 776), respectively, of patients on atorvastatin. Only 14% of the 'usual' care patients received any hypolipidaemic drugs throughout the study and 3% of them reached the NCEP LDL-C treatment goal. The cost per quaility-adjusted life-year gained with atorvastatin was estimated at $US 8350. During this study 196 (24.5%) CHD patients on 'usual' care had a CHD recurrent event or died vs. 96 (12%) CHD patients on atorvastatin; risk ratio (RR) 0.49, confidence interval (CI) 0.27-0.73, p < 0.0001. In detail, atorvastatin reduced, in comparison to 'usual' care, total mortality (RR 0.57, CI 0.39-0.78, p = 0.0021), coronary mortality (RR 0.53, CI 0.29-0.74, p = 0.0017), coronary morbidity (RR 0.46, CI 0.25-0.71, p < 0.0001), and stroke (RR 0.53, CI 0.30-0.82, p = 0.034). All subgroups of patients (women, those with diabetes mellitus, arterial hypertension, age 60 to 75 years, congestive heart failure, recent unstable angina or prior revascularisation) benefited from treatment with atorvastatin. Withdrawal of patients because of side-effects from the atorvastatin group was low (0.75%) and similar to that of the 'usual' care group (0.4%). CONCLUSIONS: Long-term treatment of CHD patients with atorvastatin to achieve NCEP lipid targets significantly reduces total and coronary mortality, coronary morbidity and stroke, in comparison to patients receiving 'usual' medical care. Treatment with atorvastatin is well tolerated and cost-effective.

Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients.

AIM: To assess the effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients free of arterial hypertension and diabetes mellitus. METHODS AND RESULTS: The study included 36 patients (25 men and 11 women, mean age 56 +/- 12 years); 18 patients had stable coronary heart disease (CHD) and 18 were free of CHD at baseline. All patients received atorvastatin (20 mg/day) for a 2-year period. Aortic stiffness was assessed by transthoracic echocardiography at baseline and 2 years later. At baseline, total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL-C/high density lipoprotein cholesterol (HDL-C) ratio were positively related to aortic stiffness (p < 0.001 for all). The mean change in lipid parameters during treatment was: total cholesterol -38%, LDL-C -46%, triglycerides -29%, and HDL-C +6%, all significant (p = 0.029 to < 0.0001). After the 2-year treatment with atorvastatin, aortic stiffness was significantly reduced by 14% (p = 0.019). An improvement of left ventricular (LV) ejection fraction by 13% (p < 0.001) and a reduction of LV mass index by 9% (p = 0.008) were also recorded. The change in aortic stiffness was similar in patients with or without CHD. CONCLUSION: Long-term treatment with atorvastatin improves aortic stiffness; this index is related to total and coronary mortality. Moreover, assessment of aortic stiffness may be useful in identifying which hypercholesterolaemic patients should be treated aggressively, regardless of CHD. The aortic stiffness effect may eventually become an index of the efficacy of lipid lowering treatment.

Attaining United Kingdom-European Atherosclerosis Society low-density lipoprotein cholesterol guideline target values in the Greek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.

The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study compared two standards (structured vs. usual care) of lipid lowering treatment in 1600 patients with coronary heart disease (CHD). Structured care aimed at achieving (with atorvastatin 10-80 mg) the low-density lipoprotein cholesterol (LDL-C) (2.6 mmol/l; 100 mg/dl) goal described in the NCEP ATP II and III guidelines for patients with CHD. Structured care was associated with a significant reduction in overall mortality and coronary events compared to usual care. In the present brief report we interpret the results of GREACE using the United Kingdom (UK) and European Atherosclerosis Society (EAS) treatment goal for LDL-C in secondary CHD prevention (3.0 mmol/l; 115 mg/dl. The mean dose of atorvastatin decreased from 24 mg to 22 mg/day. More patients achieved the UK and EAS LDL-C target (95.6 vs. 95%) in the structured care arm of the trial; 90% of the patients achieved this target with 10 or 20 mg atorvastatin. These findings may have cost implications, especially if the LDL-C target for high-risk patients will fall below those described above.

Radiation-induced intracranial meningioma and multiple cavernomas.

Brain irradiation has several well-known long-term side effects, including radiation-induced neoplasms and vasculopathy. In this case report, we describe an extremely rare case of meningioma and 15 cavernomas developing in a 29-year-old man, 19 years after cranial irradiation for posterior cranial fossa medulloblastoma. To our knowledge, this is the first case of a radiation-induced meningioma accompanied by this many radiation-induced cavernous angiomas.

Delayed persistent hyperthermia after resection of a craniopharyngioma.

OBJECTIVE AND IMPORTANCE: Disorders of thermoregulation are occasionally noticed after operations in the region of the third ventricle. Various factors are usually implicated, but the actual contribution of each of them is rather vague. Apart from the presumed derangement in the functional connections of the hypothalamic region, mechanical reasons of compression should be thoroughly considered. CLINICAL PRESENTATION: An 8.5-year-old patient was subjected to a radical excision of a craniopharyngioma compressing the third ventricle. Three months after the operation, he presented with a febrile syndrome of unknown origin. All usual investigations proved negative. INTERVENTION: A chronic subdural hygroma was evacuated, an encapsulated CSF cyst of the suprachiasmatic cistern was drained and the lamina terminalis incised resulting in a moderate control of pyrexia. The administration of chlorpromazine contributed to the final resolution of hyperthermia. CONCLUSION: Postoperative hyperthermia may result following resection of tumors of the hypothalamic floor. It should not be blindly attributed to hypothalamic dysfunction as surgical causes could be implicated as well. Chlorpromazine could be a useful adjunct to the correction of the disorder.

Atorvastatin versus four statin-fibrate combinations in patients with familial combined hyperlipidaemia.

BACKGROUND: Statin-fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia (FCHL). Nonetheless, they have not been extensively used because of the fear of side effects. Thus, a therapeutic alternative is required for this lipid disorder. OBJECTIVE: To compare the long-term (one-year) efficacy of atorvastatin monotherapy with those of four statin-fibrate combinations in 675 FCHL patients. METHODS: Patients were randomly assigned to atorvastatin monotherapy (A 20 mg/day) n = 134, or pravastatin (P 20 mg/day)+gemfibrozil (G 1200 mg/day) n = 135, simvastatin (S 20 mg/day)+G (1200 mg/day) n = 137, P (20 mg/day)+ciprofibrate (C 100 mg/day) n = 135, and S (20 mg/day)+C (100 mg/day) n = 134. RESULTS: Twelve patients on statin-fibrate combinations were withdrawn from the study because of side effects: three because of CK elevation, two because of myalgia and seven due to increase in serum transaminase levels. One patient on A was withdrawn because of persistent epigastric discomfort. Atorvastatin reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations (-45% vs. maximum -40% of S+C, and -39% vs. maximum -32% of the same combination, respectively, P < 0.001 for both), but had a lesser effect on triglycerides (-38% vs. maximum -53% of S+C, P = 0.0002) and high density lipoprotein cholesterol (6% vs. maximum 21% of S+G, P = 0.0003). The effect of A on plasma fibrinogen was analogous to that of G combinations (-8% vs. -9% of P+G and -11% of S+G, P = NS vs. baseline and among each other) and inferior to that of the ciprofibrate combinations (-8% vs. -24% of P+C, P = 0.0002 and -26% S+C, P = 0.0001). A had a lower treatment cost and better patient compliance, P = 0.04 vs. C combinations and P = 0.02 vs. G combinations. CONCLUSIONS: The data suggest that statin-fibrate combinations have a beneficial effect on all lipid parameters. Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin-fibrate combinations, but a lesser effect on HDL-C, TG and in the case of ciprofibrate combinations, fibrinogen. The clinical significance of these findings should be tested in a large, long-term survival study.

Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis.

BACKGROUND: An acute and potentially life-threatening complication of hypertriglyceridemia (HTG) is acute pancreatitis (AP). Hypertriglyceridemia, usually severe, may be primary in origin or secondary to alcohol abuse, diabetes mellitus, pregnancy, and use of drugs. STUDY: The efficacy of treatment to prevent relapses in 17 patients with AP attributed to HTG was investigated in the current prospective study. The mean follow-up period of patients was 42 months. Hypertriglyceridemia-induced AP comprised 6.9% of all patients with AP (n = 246) hospitalized in our clinic during the study (6 years). RESULTS: Causative conditions of HTG-induced AP were familial HTG in eight patients, HTG caused by uncontrolled diabetes mellitus in five, HTG aggravated by drugs in two (one by tamoxifen and one by fluvastatin), familial hyperchylomicronemia (HCM) in one, and lipemia of pregnancy in one. During the acute phase of pancreatitis, patients underwent standard treatment. Thereafter, HTG was efficiently controlled with high dosages of fibrates or a fibrate plus acipimox, except for the patient with HCM, who was on a specific diet (the only source of fat was a special oil consisting of medium chain triglyceride) and taking a high dosage of acipimox. One of the patients died during the acute phase of pancreatitis with acute respiratory distress syndrome. During follow-up, maintenance treatment was successful and only one patient relapsed, because he discontinued diet and drug treatment. CONCLUSION: Appropriate diet and drug treatment, including dose titration, of severe HTG is very effective in preventing relapses of HTG-induced AP.