L-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study.

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. L-Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of L-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive L-carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the L-carnitine/simvastatin group [-19.4%, from 52 (20-171) to 42 (15-102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [-6.7%, from 56 (26-108) to 52 (27-93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B and TAG were observed in both groups. Co-administration of L-carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels.

Comparison of switch to the highest dose of rosuvastatin vs. add-on nicotinic acid vs. add-on fenofibrate for mixed dyslipidaemia.

BACKGROUND: Use of a statin at a standard dose may be insufficient for the treatment of mixed dyslipidaemia. Whether switch to the highest dose of rosuvastatin (40 mg) or add-on nicotinic acid (NA) or fenofibrate is more efficacious remains unknown. PATIENTS AND METHODS: This was a prospective, randomised, open-label, blinded end-point (PROBE) study. We recruited 100 patients with mixed dyslipidaemia who were treated with a statin at a standard dose but had not achieved lipid targets. Patients were randomised to switch to the highest approved dose of rosuvastatin (40 mg), add-on extended release nicotinic acid (ER-NA)/l-aropiprant (LRPT) or to add-on micronised fenofibrate for 3 months. The primary end-point was the change in non-high-density lipoprotein cholesterol (non-HDL-C) levels. RESULTS: Ninety patients completed the study. Non-HDL-C decreased in all groups (by 23, 24 and 7% in the rosuvastatin, ER-NA/LRPT and fenofibrate group, respectively, p < 0.01 for all compared with baseline and p < 0.01 for all compared with fenofibrate group). Low-density lipoprotein cholesterol (LDL-C) decreased by 23 and 19% in the rosuvastatin and ER-NA/LRPT group, respectively (p < 0.01 compared with baseline), but not in the add-on fenofibrate group. Add-on ER-NA/LRPT was associated with the greatest HDL-C increase, while add-on ER-NA/LRPT and add-on fenofibrate were associated with the greatest triglyceride decrease. Twenty-four per cent of patients initially randomised to add-on ER-NA/LRPT dropped out because of side effects. CONCLUSIONS: In conclusion, switch to the highest dose of rosuvastatin and add-on ER-NA/LRPT may be better options compared with add-on fenofibrate for the management of patients with mixed dyslipidaemia not on treatment goals with a statin at a standard dose.

Lysis syndrome during therapy of visceral leishmaniasis.

INTRODUCTION: Lysis syndrome is a constellation of metabolic disorders usually seen after the initiation of chemotherapy for rapidly proliferating malignancies (tumor lysis syndrome). Reported herein is a tumor lysis-like syndrome after the initiation of anti-infective therapy for visceral leishmaniasis. PATIENTS AND METHODS: Ten consecutive patients with visceral leishmaniasis were administered liposomal amphotericin B. Levels of serum uric acid, phosphate, creatinine, blood urea nitrogen, potassium, calcium, and magnesium were evaluated prior to as well as 4 and 30 days following the initiation of treatment. RESULTS: During the 4th post-treatment day significant increases in the levels of serum uric acid, phosphate, creatinine, and blood urea nitrogen were seen, while the levels of calcium, potassium, and magnesium were not significantly altered. Patients were treated by hydration, urine alkalization, and administration of allopurinol as needed. A recovery of metabolic abnormalities was recorded 1 month later, although some patients had evidence of residual injury. CONCLUSION: A lysis syndrome may complicate the treatment of visceral leishmaniasis. Awareness of this complication can lead to the initiation of prophylactic treatment as well as to early recognition and management of this syndrome in susceptible patients.

Effects of thyroid dysfunction on lipid profile.

Thyroid dysfunction has a great impact on lipids as well as a number of other cardiovascular risk factors. Hypothyroidism is relatively common and is associated with an unfavorable effect on lipids. Substitution therapy is beneficial for patients with overt hypothyroidism, improving lipid profile. However, whether subclinical hypothyroidism should be treated or not is a matter of debate. On the other hand, hyperthyroidism can be associated with acquired hypocholesterolemia or unexplained improvement of lipid profile. Overall, thyroid dysfunction should be taken into account when evaluating and treating dyslipidemic patients.

Acute infection with Epstein-Barr virus is associated with atherogenic lipid changes.

OBJECTIVE: To evaluate the effects of acute infection with Epstein-Barr virus (infectious mononucleosis, IM) on lipids and lipoproteins. METHODS: Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), apolipoproteins (apo) A-I, B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with IM on diagnosis and 4 months after the resolution of febrile illness and in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1) as well as levels of several cytokines were determined. LDL subclass analysis was performed with the Lipoprint LDL System. RESULTS: Twenty-nine patients (16 males, aged 24.3±14.6 years) and 30 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB, apoC-III and Lp(a) levels were lower at baseline whereas apoB/apoA-I ratio, TG levels and CETP activity were elevated compared with 4 months later. At baseline, higher levels in cytokines and the cholesterol concentration of small-dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of Lp-PLA2 and PON1 were similar at baseline and 4 months later. Four months after the resolution of IM levels of TGs, apoE, apoC-III, Lp(a), sdLDL-C and cytokines as well as LDL particle size, apoB/apoA-I ratio, CETP and Lp-PLA2 activities were similar to controls. PON1 activities both at baseline and 4 months later were lower in patients compared with controls. CONCLUSIONS: IM is associated with atherogenic changes of lipids and lipoproteins that are partially restored 4 months after its resolution.

Fenofibrate in primary biliary cirrhosis: a pilot study.

BACKGROUND: Most patients with primary biliary cirrhosis (PBC) are treated with ursodeoxycholic acid (UDCA); however, some do not respond fully. PBC is also associated with dyslipidemia, but a link with vascular risk has not been confirmed. METHODS AND RESULTS: In this study we compared UDCA monotherapy with fenofibrate plus UDCA in PBC patients with incomplete biochemical response to UDCA monotherapy for >/= 8 months. Ten patients (57.2+/-13.3 years old) with PBC and persistent elevations of liver enzymes after treatment with UDCA (600 mg/day) were randomized to continue UDCA (4 patients) or to receive micronized fenofibrate (200 mg/day) plus UDCA (6 patients) for 8 weeks. Significant reductions in total cholesterol, triglycerides and non-high density lipoprotein cholesterol were observed in the combination treatment group. The serum activities of alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotranferase also decreased in this group compared with baseline (-32.6%; p=0.012, -44%; p=0.031 and -16.9%; p=0.029, respectively). In contrast, no significant alterations in liver enzymes or lipid profile were observed in patients who continued UDCA monotherapy. The changes in the lipid and enzyme variables differed significantly (p<0.03) between the 2 groups. Fenofibrate was well tolerated. CONCLUSIONS: The administration of fenofibrate plus UDCA seems to be safe and may improve lipid and liver indices in patients with PBC who do not respond fully to UDCA monotherapy. Whether the improved lipid profile translates into a decreased risk of vascular events remains to be established.

Aliskiren, a direct renin inhibitor, in clinical practice: a new approach in the treatment of hypertension.

OBJECTIVE: Arterial hypertension is an important risk factor for the development and progression of cardiovascular disease (CVD). The renin angiotensin aldosterone system (RAAS) plays a crucial role in the pathophysiology of hypertension and associated complications. Direct renin inhibitors (DRIs) are novel antihypertensive drugs which inhibit the first step of RAAS. Aliskiren is the first orally active DRI approved as monotherapy or in combination with other antihypertensive agents for the treatment of hypertension. SCOPE: This article reviews the efficacy and safety of aliskiren as monotherapy and in combination with other antihypertensive agents and comments on its potential role in clinical practice. METHODS: Relevant articles were identified through a PubMed search (up to 17 August 2009). FINDINGS: Aliskiren, used alone or in combination with other antihypertensive agents, has a favourable effect on blood pressure (BP). Specifically, aliskiren is equally effective with other RAAS inhibitors and probably superior to hydrochlorothiazide in the reduction of systolic and diastolic BP. The combination of aliskiren with other antihypertensive drugs seems to be an effective and safe therapeutic option. In addition, aliskiren may have favourable effects in terms of ameliorating several microvascular and macrovascular complications of hypertension and diabetes. CONCLUSIONS: Aliskiren appears to be an effective and safe antihypertensive drug. Whether the BP lowering effect of aliskiren is associated with improvements in cardiovascular outcomes remains to be elucidated.

Drug combinations for dyslipidemia and obesity treatment in metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of risk factors, each one individually associated with increased cardiovascular disease risk. Treatment of all components of MetS is expected to result in reduced risk. Treatment of MetS mainly includes lifestyle changes. In addition, drug therapy may be considered, especially combinations of different drugs, in order to tackle all the features of MetS. We review the therapeutic strategies currently used for obesity and dyslipidemia treatment in patients with MetS, with a focus on drug combinations.

Are the pleiotropic effects of telmisartan clinically relevant?

Hypertension is one of the major risk factors for cardiovascular disease. Angiotensin receptor blockers (ARBs) are a class of antihypertensive drugs with established efficacy and favorable safety profile. Telmisartan, a member of the ARB family, holds some additional traits which differentiate it from the rest ARBs. A pivotal role in these characteristics plays its ability to partially activate the peroxisome proliferator activated receptor-gamma, which in turn controls a number of metabolism-related genes. Indeed, telmisartan has shown a number of pleiotropic effects in experimental and clinical studies. These include the amelioration of insulin resistance, improvement of lipid profile and favorable fat redistribution. Moreover, telmisartan has been associated with beneficial effects on vascular function, cardiac remodeling and renal function. However, do all these pleiotropic effects translate into clinical benefit? Recent studies have tried to answer this question with promising but not definitive results.

Persistence of an atherogenic lipid profile after treatment of acute infection with Brucella.

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and levels of cytokines [interleukins (IL)-1beta, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA(2) activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA(2) activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.

How safe is the use of thiazolidinediones in clinical practice?

BACKGROUND: Thiazolidinediones (TZDs) are widely used antidiabetic drugs with proven efficacy regarding mainly surrogate markers of diabetes management. However, efficacy on surrogate markers may not always translate into benefits in clinical outcomes. Thiazolidinediones are usually well tolerated; however, their use may be associated with several adverse effects. The first TZD, troglitazone, was withdrawn from the market owing to serious hepatotoxicity. However, this does not seem to be the case with newer TZDs. OBJECTIVE: The aim of the present review is to discuss the safety profile of this drug class. METHODS: We searched PubMed up to July 2008 using relevant keywords. CONCLUSIONS: Common side effects associated with TZDs include edema, weight gain, macular edema and heart failure. Moreover, they may cause hypoglycemia when combined with other antidiabetic drugs as well as decrease hematocrit and hemoglobin levels. Increased bone fracture risk is another TZD-related side effect. Thiazolidinediones tend to increase serum low density lipoprotein cholesterol levels, with rosiglitazone having a more pronounced effect compared with pioglitazone. Moreover, rosiglitazone increases low density lipoprotein particle concentration in contrast to pioglitazone where a decrease is observed. Rosiglitazone has been associated with an increase in myocardial infarction incidence. On the other hand, pioglitazone may reduce cardiovascular events. Overall, TZDs are valuable drugs for diabetes management but physicians should keep in mind that they are associated with several adverse events, the most prominent of which is heart failure.

Effects of hormonal treatment on lipids in patients with cancer.

Patients with malignant disease may need hormonal therapy as primary or adjuvant treatment or for palliation. Oestrogens usually decrease serum levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), increase high density lipoprotein cholesterol (HDL-C) concentration, but induce an elevation in serum triglyceride (TG) levels. Progestogens in the short-term decrease TC, LDL-C and HDL-C concentrations, and increase TG levels. In long-term treatment, progestogens usually have a small impact on lipid profile. Tamoxifen induces a decrease in TC and LDL-C levels, an increase in TG concentration, whereas either an increase, decrease or no change has been reported for HDL-C levels. Aromatase inhibitors induce an elevation, reduction or no change in lipid variables. These results depend mainly on the trial design, i.e. whether patients received prior treatment with tamoxifen or not and the duration of therapy. Gonadorelin analogues increase all lipid variables, but LDL-C alterations are usually non-significant. Anti-androgens usually decrease TC, LDL-C and HDL-C levels, whereas TG alterations vary. Information regarding the effects on lipid profile of somatostatin analogues is available almost exclusively in patients with acromegaly. In these patients somatostatin analogues usually induce no change or a decrease in TC and LDL-C levels, whereas they increase HDL-C and decrease TG serum concentrations. Oncologists should consider the lifestyle changes, and if needed hypolipidemic treatment, used to lower cardiovascular risk in non-cancer patients. Tamoxifen may rarely cause serious TG-related side effects, like acute pancreatitis.

Effect of rimonabant, micronised fenofibrate and their combination on cardiometabolic risk factors in overweight/obese patients: a pilot study.

OBJECTIVE: To assess the effect of rimonabant, micronised fenofibrate and their combination on anthropometric and metabolic parameters in overweight/obese patients with dyslipidaemia. METHODS: All patients (n = 30) received a hypocaloric diet ( approximately 600 kcal/day deficit) and were randomly allocated to receive open-label rimonabant (R) 20 mg/day (n = 10), micronised fenofibrate (F) 200 mg/day (n = 10) or rimonabant 20 mg/day plus fenofibrate 200 mg/day (RF) (n = 10). Anthropometric and metabolic parameters were assessed at baseline and 3 months after treatment initiation. RESULTS: Compared with baseline similar significant reductions in body weight, body mass index and waist circumference were observed in the R (-6, -5 and -5%, respectively; p < 0.01) and RF group (-5% for all, p < 0.05), while improvements in these parameters were smaller in the F group (-2, -2.5 and -2%, respectively; p < 0.05). Triglycerides were reduced by 18% in the R group (p = NS), by 39% in the F group (p < 0.001) and by 46% in the RF group (p < 0.05). Importantly, combination treatment resulted in a 42% increase in high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05), while HDL-C was not significantly altered in the two monotherapy groups. Subsequently, a more pronounced increase in apolipoprotein A-I (ApoA-I) levels (+25%) was observed in the RF group compared with changes in both monotherapy groups (p < 0.0001 vs R and p < 0.005 vs F group). Low-density lipoprotein cholesterol (LDL-C) levels were not significantly altered in any group. Apolipoprotein B (apoB) levels were reduced in all groups and this reduction was significantly more pronounced in the RF group (p < 0.05 vs baseline as well as p < 0.005 and p < 0.01 for RF vs R and F groups, respectively). ApoB/apoA-I ratio decreased by 3% with R (p = NS), by 18% with F (p < 0.05) and by 40% with RF treatment (p < 0.01). Total cholesterol to HDL-C ratio decreased by 20% with F (p < 0.0001) and by 33% with RF therapy (p < 0.005), while it was not significantly altered in R group. CONCLUSION: The combination of rimonabant and fenofibrate may further improve metabolic parameters in overweight/obese patients with dyslipidaemia compared with each monotherapy. This improvement is particularly pronounced for HDL-C levels.

Effects of sibutramine plus verapamil sustained release/trandolapril combination on blood pressure and metabolic variables in obese hypertensive patients.

OBJECTIVE: The management of obese hypertensive subjects may require the administration of anti-obesity and antihypertensive drugs. Sibutramine use has raised concerns regarding a potential increase in subjects' blood pressure and heart rate. The primary end-points of this study were an evaluation of the effect of sibutramine together with a verapamil sustained release/trandolapril combination tablet versus verapamil sustained release/trandolapril alone on the blood pressure and heart rate in obese hypertensive patients. RESEARCH DESIGN/METHODS: Patients received a low-fat low-calorie diet and were randomly allocated to open-label verapamil sustained release/trandolapril 180/2 mg (n = 26) or sibutramine 10 mg together with verapamil sustained release/trandolapril 180/2 mg (n = 28) daily for 6 months. RESULTS: Significant reductions in the subjects' systolic blood pressure and diastolic blood pressure were observed in both groups (p < 0.01 versus baseline). At 6 months a greater fall in blood pressure was observed in the sibutramine/verapamil sustained release/trandolapril group compared with the verapamil sustained release/trandolapril group (systolic blood pressure 21.9 +/- 8.1 versus 15.9 +/- 12.3 mmHg and diastolic blood pressure 15.7 +/- 8.1 versus 9.1 +/- 9.9 mmHg) but this was only significant (p = 0.03) for diastolic blood pressure. The subjects' heart rate did not change significantly in any group. No significant sibutramine-associated attenuation of blood pressure reduction was observed during the study. The sibutramine/verapamil sustained release/trandolapril treatment resulted in significantly greater improvement in the subjects' anthropometric variables, homeostasis model assessment and lipid profiles compared with verapamil sustained release/trandolapril administration. The subjects' small dense low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and visfatin plasma levels were only measured in the sibutramine/verapamil sustained release/trandolapril group (all decreased by p < 0.05 versus baseline). CONCLUSIONS: The sibutramine/verapamil sustained release/trandolapril combination in obese hypertensive patients significantly reduced their blood pressure and improved their anthropometric and metabolic variables without affecting the heart rate.

Sitagliptin in clinical practice: a new approach in the treatment of type 2 diabetes.

BACKGROUND: Sitagliptin is a novel agent for the treatment of type 2 diabetes either as monotherapy or in combination with metformin or a thiazolidinedione. OBJECTIVE: To review the efficacy and safety of sitagliptin in clinical trials and comment on drug interactions and safety issues arising from its use. METHODS: Relevant articles were identified through a PubMed search (up to May 2008). RESULTS/CONCLUSIONS: Sitagliptin either used alone or in combination with other hypoglycemic agents has a favorable glucose-lowering effect and safety profile. It has been associated with few side effects, mainly involving the gastrointestinal system and with a low incidence of hypoglycemia, while it generally demonstrated a neutral effect on body weight. Sitagliptin is a safe alternative or complementary option for patients with type 2 diabetes who do not reach the recommended glycosylated hemoglobin level with lifestyle interventions and/or current oral antidiabetic agents.

Pleiotropic effects of thiazolidinediones.

BACKGROUND: Insulin resistance and hyperglycemia characterize type 2 diabetes mellitus. Type 2 diabetes mellitus is usually accompanied by concomitant disorders, such as dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones are antidiabetic drugs that increase insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma. There is evidence that thiazolidinediones exert a number of pleiotropic effects that may play an important role in the treatment of type 2 diabetes mellitus. OBJECTIVE: The purpose of the present article was to review the 'pleiotropic' effects of thiazolidinediones (i.e., their effects beyond glucose lowering). METHODS: The study involved searching PubMed up to February 2008 using relevant keywords. CONCLUSIONS: Thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid and they may also delay the progression of atherosclerosis. The effects on the lipid profile differ between the two thiazolidinediones studied with pioglitazone having more positive effects compared with rosiglitazone. Furthermore, thiazolidinediones improve diabetic complications, such as diabetic nephropathy and non-alcoholic fatty liver disease. Thiazolidinediones may also play a role in other diseases, such as polycystic ovary syndrome. These pleiotropic effects may prove to be clinically relevant. There has been recent debate about the possible differences between the two thiazolidinediones in terms of cardiovascular disease outcome. In this context, differences in the lipid effects between the two drugs may be relevant.

Fibrate-associated adverse effects beyond muscle and liver toxicity.

Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are liver and muscle related. These effects are less well known but are clinically relevant.

Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia.

OBJECTIVE: Hypercholesterolaemia is a major risk factor for atherosclerosis and coronary heart disease. Treatment with lipid lowering agents reduces the risk of vascular events. Colesevelam is a novel bile acid sequestrant (BAS) indicated for the treatment of hypercholesterolaemia, either as monotherapy or in combination with statins. SCOPE: This article reviews the efficacy, tolerability and safety of colesevelam in clinical practice. The literature search was based on a PubMed search up to January 2008. FINDINGS: Colesevelam, used alone or in combination with other hypolipidaemic agents (statins, ezetimibe and fenofibrate), has an overall favourable effect on lipid profile. Specifically, colesevelam reduces total and low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B levels and increases high-density lipoprotein cholesterol and apolipoprotein AI. However, colesevelam may slightly raise triglyceride levels. Colesevelam can improve glycaemic control in diabetic patients. Moreover, it may have anti-inflammatory properties, as it can reduce high sensitivity C-reactive protein concentration. Colesevelam almost lacks the intense side effects of previously used BASs, thus resulting in better patient compliance. However, the dose regimen consisting of up to 7 tablets/day and high cost may limit its use. CONCLUSIONS: Colesevelam is a safe alternative for those intolerant to other lipid lowering medication. This BAS also provides an option for patients who do not reach their LDL-C goal despite treatment with a statin.

Ezetimibe-associated adverse effects: what the clinician needs to know.

OBJECTIVE: Ezetimibe is a relatively new lipid lowering agent, which is indicated for the treatment of primary hypercholesterolaemia, either as monotherapy or in combination with other hypolipidaemic drugs. The objective of the present article was to review the side effects attributed to ezetimibe administration and discuss their possible underlying mechanisms. Moreover, we aimed to comment on the possible drug interactions of ezetimibe and present current guidelines regarding its safe use. METHODS: Relevant articles were identified through a PubMed search (up to June 2007). RESULTS: Compelling evidence from the majority of the data reviewed here showed that adverse effects associated with ezetimibe use are few and mild without having been associated with serious clinical outcomes. In most studies ezetimibe has not been associated with increased rates of myopathy or rhabdomyolysis, whether used alone or in combination with statins, although there have been some case reports of myopathy attributed to this agent. Moreover, ezetimibe has been associated with mild elevations of liver transaminases, mainly in combination with a statin. Other side effects are extremely rare. It should be noted, however, there are no long-term safety data or outcome studies for ezetimibe yet. CONCLUSIONS: Ezetimibe is a safe alternative option for hyperlipidaemic patients intolerant to other lipid lowering drugs as well as a beneficial supplementary agent for patients who do not reach the recommended serum cholesterol level with their current hypolipidaemic treatment. However, as is the case with all new medications, physicians should be alert to recognise adverse effects associated with ezetimibe and report them to regulatory authorities.

The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome.

OBJECTIVE: We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS). METHODS: Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay. RESULTS: We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy. CONCLUSION: OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.