Exorcising ghosts and unwelcome guests.
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Authorship↗
Biomedical subjects
Stella S Daskalopoulou
Publications and source records attributed to Stella S Daskalopoulou.
Ezetimibe/simvastatin single tablet versus rosuvastatin in patients with hypercholesterolemia.
Recent guidelines recommend strict goals for low density lipoprotein cholesterol (LDL-C) (70-100 mg/dL; 1.8-2.6 mmol/L). These goals were set following the publication of several trials. In the current issue of the journal, a study compares different doses of the combination tablet (ezetimibe/simvastatin) with statin monotherapy (rosuvastatin). In keeping with previous literature, the combination therapy was more effective in achieving LDL-C goals. This editorial comments on the potential disadvantages of using monotherapy with high-dose statins and considers the issue of statin-induced proteinuria. Combination therapy may need to be increasingly used to achieve the LDL-C targets set by recent guidelines.
Anticholesteremic Agents↗
Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe.
Lowering serum cholesterol levels reduces the risk of coronary heart disease (CHD)-related events. Statins are commonly prescribed as first-line treatment but many patients at high-risk for CHD still fail to reach their cholesterol or low-density lipoprotein cholesterol (LDL-C) goals with statin monotherapy. National and international guidelines for the prevention of CHD recommend the modification of lipid profiles and particularly LDL-C [e.g. the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III; 2001) and Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (2003) Guidelines]. Several recent clinical trials indicated an added benefit from aggressive lowering of LDL-C levels. Based on these findings, the NCEP ATP III revised the LDL-C target from < 100 mg/dL (2.6 mmol/L) to < 70 mg/dL (1.8 mmol/L) (optional target) for very high-risk patients and < 130 mg/dL (3.4 mmol/L) to < 100 mg/dL (2.6 mmol/L) for moderately high-risk patients. For patients who fail to achieve their LDL-C target, inhibiting the two main sources of cholesterol - synthesis and uptake - can produce more effective lipid lowering, allowing more patients to reach their LDL-C goal. Ezetimibe is a highly-selective inhibitor of cholesterol absorption and simvastatin is an evidence-based inhibitor of cholesterol synthesis. The LDL-C-lowering efficacy of targeting both major sources of cholesterol with ezetimibe plus simvastatin was demonstrated in several multicentre, double-blind, placebo-controlled trials in patients with hypercholesterolaemia. For patients who do not reach their cholesterol goal with a statin, adding ezetimibe 10 mg significantly reduces LDL-C compared with statin monotherapy. Thus, this treatment option may help patients reach the new 'stricter' cholesterol goals. This review, based on a Medline database search from January 2000 to August 2005, considers the LDL-C-lowering efficacy of ezetimibe and discusses the role of this agent for patients who fail to achieve guideline cholesterol goals with statin monotherapy.
Anticholesteremic Agents↗
Definitions of metabolic syndrome: Where are we now?
The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidaemia and is associated with an increased risk of vascular events. Since the initial description of the MetS, several expert groups produced different definitions. This variability led to confusion and absence of comparability between studies. Although there is agreement that the MetS is a major public health challenge worldwide and consistent evidence stresses the need for intervention, the definition of the syndrome remains a matter of debate. This review considers the different definitions of the MetS. These include those proposed by the World Health Organisation, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program Adult Treatment Panel III, the American College of Endocrinology and American Association of Clinical Endocrinologists and the latest International Diabetes Federation definition which includes ethnic-specific waist circumference cut-off points. These definitions share several features but also include important differences; all have limitations. Selected (after a Medline search) studies comparing the different definitions are also considered. There is a need for a standardised definition of the MetS. Furthermore, a definition tailored for children and adolescents is essential. Prospective long-term studies are needed to validate the prognostic power of these definitions. As new information becomes available the definition of the MetS might be further modified.
Adolescent↗
Review on the value of graduated elastic compression stockings after deep vein thrombosis.
Graduated elastic compression stockings (GECS) are commonly used in the primary prevention of deep vein thrombosis (DVT); however, their role in preventing recurrent DVT and also post-thrombotic syndrome is less well established. The aim of this review was to investigate the effect of GECS after DVT. A literature search was performed by two independent searchers in order to identify randomised controlled trials on the effect of GECS in preventing recurrent DVT and post-thrombotic syndrome. Four randomised trials, including 537 patients, were identified. Two of the studies demonstrated that below-knee GECS significantly reduced post-thrombotic syndrome during follow-up, while a smaller study showed equivocal results. GECS reduced the incidence of post-thrombotic syndrome from 54% to 25.2% [relative risk (RR) 0.47, 95% confidence interval (CI) 0.36-0.61] with the number needed to treat (NNT) being 4 (95% CI 2.7-5.0). The rate of recurrent asymptomatic DVT was also significantly reduced by GECS (RR 0.20, 95% CI 0.06-0.64; NNT 5); the reduction in symptomatic DVT was not significant (RR 0.79, 95% CI 0.50-1.26; NNT 34). In conclusion, there is level Ia evidence to suggest that GECS can significantly reduce the incidence of post-thrombotic syndrome (PTS) after DVT, and therefore these should be routinely prescribed. The evidence for recurrent DVT is less conclusive. Further research is needed towards standardising PTS diagnostic criteria and evaluating more effective preventive measures after DVT.
Bandages↗
Effect of statins and aspirin alone and in combination on clinical outcome in dyslipidaemic patients with coronary heart disease. A subgroup analysis of the GREACE study.
DECLARATION OF INTEREST: The GREACE study was conducted independently; no Company or Institution has supported it financially. Some of the authors have attended conferences and participated in other trials sponsored by various pharmaceutical companies. We assessed the possible 'synergy' of statins and aspirin (ASA) in reducing vascular events in patients with coronary heart disease, in a post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. All patients (n = 1600) were divided into four groups according to long-term treatment: Group A (n = 787; statin + ASA), B (n = 93; statin - no ASA), C (n = 599; no statin - on ASA) and D (n = 121; no statin - no ASA). From all patients 692 were either on a statin or ASA monotherapy (Groups B + C). Relative risk reductions (RRRs) in 'all events' (primary endpoint) between groups were assessed. During the 3-year follow-up there were 292 cardiovascular events; 92 (12% of patients) in Group A, 14 (15%) in group B, 144 in Group C (24%) and 42 events in Group D (35%). The total number of events in Group B + C was 158 (23%). The RRRs in the primary endpoint were: Group A versus B 24% (P = 0.1912), A versus C 51% (P < 0.0001), A versus B + C 49% (P < 0.0001) and A versus D 71% (P < 0.0001). The RRRs in Group B versus C was 36% (P = 0.0431) and B versus D 57% (P = 0.0012), while in C versus D 33% (P = 0.0084). Our findings show that statins and ASA have an additive effect in reducing cardiovascular events. Aggressive statin use in the absence of ASA also substantially reduced cardiovascular events. Treatment with ASA in the absence of statin use reduced clinical events in comparison to patients not treated with either drug.
Adult↗
Lipid-lowering therapy in patients with peripheral arterial disease.
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Cardiovascular Diseases↗
A review of the lipid-related effects of fluvastatin.
BACKGROUND: Statin therapy has been shown to significantly decrease vascular events and overall mortality in primary and secondary prevention trials. This review considers the pharmacology, nonlipid-lowering effects and clinical trial evidence of fluvastatin based on a survey of PubMed entries. FINDINGS: Recent clinical data show that treatment with fluvastatin is associated with a variety of benefits in different high-risk populations along with a good safety profile. Fluvastatin exerts non-lipid lowering-associated pleiotropic effects in both clinical and experimental studies. Furthermore, an extended-release formulation of fluvastatin with a favourable pharmacokinetic profile is available. CONCLUSION: Treatment with fluvastatin offers a convenient, safe and evidence-based approach to managing dyslipidaemias and preventing vascular events.
Coronary Artery Disease↗
The involvement of professional medical writers in medical publications.
In this editorial, we comment on the European Medical Writers Association (EMWA) guidelines and the accompanying Delphi study published in this issue of Current Medical Research and Opinion. These articles deal with 'ghost writing' and the role of professional writers. We propose that the interaction between professional writers and authors is defined along the following principles: Guarantee: are the authors guarantors of the article? Advice: was the professional writer 'advised' by the author(s) before, as well as after, starting the assignment? Were the overall conclusions defined by the author(s)? Transparency: the contribution of professional writers should be acknowledged (we provide a draft statement). Expertise: does the professional writer have sufficient knowledge in the relevant specific field? The initials of these headings form the word ' GATE '. Therefore, we called them the ' GATE principles '. We also discuss suggestions for the accreditation of professional writers in specific fields. Professional writers play a useful role but this has to be clearly defined so as to achieve high ethical and scientific standards.
Accreditation↗
Peripheral arterial disease: a missed opportunity to administer statins so as to reduce cardiac morbidity and mortality.
Peripheral arterial disease (PAD) is a common condition associated with an increased risk of coronary heart disease, myocardial infarction and stroke. It follows that PAD merits aggressive preventive treatment that includes lipid lowering drugs (mainly statins). This review summarises the current knowledge concerning the use and mechanisms of action of statins in patients with PAD. Statins not only lower the risk of vascular events, but they also improve the symptoms associated with PAD. There is also evidence that statins reduce surgical mortality and improve graft patency and limb salvage. Because of the high risk, a more aggressive goal [i.e. low density lipoprotein cholesterol (LDL-C) of 70 mg/dl; 1.8 mmol/l] [National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), revised guidelines 2004] should be considered to maximally reduce the atheroma burden and related events. Not all statins can achieve this LDL-C target. Furthermore, there may be a need to use an additional lipid lowering drug so as to achieve the LDL-C goal and benefit from the different modes of action. Statins exert beneficial pleiotropic effects on haemostasis, the vasculature and inflammatory markers. There is also evidence that statins improve renal function (the plasma creatinine level is considered as an emerging vascular risk factor). Since PAD patients often take several drugs, there is a need to carefully consider their selection so as to maximize benefits and minimize adverse effects. Patients with PAD often do not receive adequate lipid lowering treatment. This situation needs to change.
Arteries↗
Clinical relevance of postprandial lipaemia.
Several studies showed that after a fatty meal, plasma triglyceride (TG) levels are higher in patients with coronary heart disease. This abnormality may explain why some individuals develop atherosclerotic disease despite normal fasting lipid values. TG-rich lipoproteins are involved in atherosclerosis and thrombosis. TG, remnant-like particle (RLP) cholesterol (RLP-C) and RLP-TG increase after fat load and could contribute to atherothrombosis. Postprandial lipaemia is not a uniform abnormality. Its pathophysiology is not yet entirely clarified; possibly, the response to dietary fat is a polygenic phenomenon. However, a link with insulin resistance is likely; this link as well as that with obesity is discussed. A substantial part of life is spent in the postprandial state. Therefore, several investigators described fat load tests. However, it is still difficult to establish normal postprandial TG ranges since only small numbers of subjects were studied and there is as yet no standardised method. A more simplified fat load test should be established for 'routine' use. In this review, we consider the metabolic features, prevalence and management of postprandial lipaemia. Treatment may involve lifestyle measures as well as the use of lipid lowering (e.g. fibrates or statins), weight reducing and hypoglycaemic drugs.
Cholesterol↗
Fenofibrate: metabolic and pleiotropic effects.
Disturbances of lipoprotein metabolism represent one of the most important risk factors for vascular events. However, dyslipidaemic patients often have a number of additional abnormalities (such as endothelial dysfunction, hypertension, low-grade inflammation, haemostatic abnormalities and hyperuricaemia) that may accelerate the atherosclerotic process. Thus, the ideal lipid-modifying drug, along with exerting beneficial effects on lipoprotein metabolism, should also improve these coexisting disturbances. Fibric acid derivatives (fibrates) are a class of lipid-modifying drugs mainly used in patients with elevated triglyceride levels. These drugs mainly exert their actions via the activation of specific nuclear receptors called peroxisome proliferator-activated receptors alpha (PPARalpha). In this review, we summarize the current evidence suggesting that fenofibrate, one of the most widely used fibric acid derivatives, along with its well established actions on lipids also exerts several other antiatherogenic actions. Based on recently published studies, fenofibrate is a useful option for patients with primary combined dyslipidaemias or secondary dyslipidaemias, such as those associated with diabetes mellitus, metabolic syndrome or HIV infection. Additionally, in cases of refractory dyslipidaemia, the combination of fenofibrate with statins is a therapeutic option.
Anti-Inflammatory Agents↗
Endothelin-1 and human platelets.
There is conflicting evidence regarding the effect of endothelin-1 (ET-1) on platelets. Some studies show that ET-1 activates platelets, others show platelet inhibition with ET-1 and some studies did not detect an effect of ET-1. These conflicting results may be due to complex interactions between platelet ET(A) and ET(B) receptors. ET-1 antagonism may emerge as an important therapeutic strategy in the management of several vascular disorders. However, to date the only prescribed ET-1 antagonist is bosentan for pulmonary arterial hypertension. Bosentan is a 'dual' ET-1 antagonist (i.e. it acts on both ET(A) and ET(B) receptors). Whether this action involves an effect on platelets remains to be established. In this review some of the studies describing the effect of ET-1 on human platelets are discussed. Vascular diseases where ET-1 is implicated are also considered.
Animals↗
The impact of serum uric acid on cardiovascular outcomes in the LIFE study.
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Antihypertensive Agents↗
Low molecular weight heparins: the optimal treatment for venous thromboembolism.
Venous thromboembolism (VTE) is a common vascular complication that requires immediate as well as long-term treatment. Unfractionated heparin (UFH), followed by oral anticoagulants (OAs), is of proved efficacy in the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). However, low molecular weight heparins (LMWHs) have successfully replaced UFH both in the prevention and in the initial treatment of DVT and PE. Recent trials evaluated the efficacy and safety of LMWH therapy as an alternative to vitamin K antagonists in long-term VTE secondary prophylaxis for all patients and in specific subgroups. LMWHs differ considerably from each other. These agents were studied separately, administered according to various protocols, in various doses and for different duration of treatment. Results from prospective randomized trials, conducted during the last decade, indicate that LMWHs are at least as effective and yet safer than OAs in the long-term treatment of VTE. In this brief overview, we consider the potential advantages of treatment with LMWH in patients with VTE.
Heparin, Low-Molecular-Weight↗
Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.
BACKGROUND: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100 mg/dL (2.6 mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. This study demonstrated significant reductions in morbidity and mortality associated with active dose titration of atorvastatin and structured management of dyslipidaemia. METHODS AND RESULTS: Intention-to-treat analysis (Cox proportional hazards model) was used to assess the relationship between lipid values and coronary events. Higher levels of LDL-C at baseline were associated with a greater risk of subsequent events among patients randomized to usual care. Reducing the LDL-C and the non-high density lipoprotein cholesterol (non-HDL-C) level to the National Cholesterol Educational Program (NCEP) Adult Treatment Panel (ATP) III goals required greater doses of atorvastatin for the higher baseline quartile of LDL-C. During the study there was a greater reduction in the risk of coronary heart disease (CHD) events in atorvastatin-treated patients who were in the highest quartile of LDL-C at baseline, after achieving the LDL-C treatment goal, in comparison to the usual care patients in the highest baseline LDL-C quartile. CONCLUSIONS: Achieving the NCEP ATP III LDL-C and non-HDL-C goals by titrating up the dose of atorvastatin was associated with a significant reduction in vascular events in patients with CHD. The greatest benefit was seen in those patients with the highest baseline LDL-C levels.
Aged↗
Clopidogrel and vascular disease prevention.
In this editorial we consider some aspects of the use of clopidogrel in current clinical practice. Clopidogrel has replaced ticlopidine as an alternative to aspirin. Among the problems with the use of antiplatelet agents is aspirin intolerance. The options for these patients are discussed; these include using clopidogrel. Clopidogrel may be especially effective in patients with peripheral arterial disease. However, this impression requires confirmation in appropriately designed trials. We also consider the effect of antiplatelet agents on growth factor release by platelets and of clopidogrel on the inflammatory process. Clopidogrel is a useful, evidence-based, antiplatelet agent.
Clopidogrel↗
Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study.
AIMS: To estimate the prevalence of vascular disease (coronary heart disease/stroke/peripheral arterial disease) in individuals with the metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) when compared with subjects without the MetSyn. PATIENTS AND METHODS: A cross-sectional analysis of a representative sample of Greek adults (n = 4153), men and women (49% and 51%, respectively), living in urban, semi-urban and rural areas (54%, 25% and 21%, respectively). The National Cholesterol Education Program-Adult Treatment Panel III definition of the MetSyn was used. RESULTS: The age-adjusted prevalence of the MetSyn was 23.6% [95% confidence interval (CI) = 22.4%-25.1%]; this was similar in men and women. The fully adjusted prevalence of vascular disease in those with the MetSyn (n = 984) was 29.4%, significantly higher than in those without (n = 3169, 9.6%, p < 0.0001), while subjects without both the MetSyn and DM had the lowest vascular disease prevalence (n = 3035, 8.9%). Subjects with the MetSyn but no DM (n = 674) had a vascular disease prevalence of 24.1% (p < 0.0001 vs. those without the MetSyn), which was similar to that in subjects with DM without the MetSyn (n = 134, 25.4%), but lower than in those with both the MetSyn and DM (n = 310, 40.7%, p < 0.0001 vs. all). In comparison to those without the MetSyn [odds ratio (OR) = 1], the ORs of prevalent vascular disease, after multivariate analysis for age, sex and components of the MetSyn, and antiatherosclerotic drugs were: all MetSyn = 1.94 (95% CI = 1.35-2.47), with both MetSyn and DM = 3.04 (95% CI = 1.98-4.11) and with MetSyn but no DM = 1.48 (95% CI = 1.12-1.92). CONCLUSIONS: The prevalence of vascular disease was markedly increased in the presence of the MetSyn. Those with both the MetSyn and DM had the highest prevalence of vascular disease, followed by those with the MetSyn without DM. Probably MetSyn without DM should be considered as a coronary heart disease-risk equivalent in future guidelines. This initiative would reset treatment targets and potentially provide additional benefit in patients with the MetSyn.
Arteriosclerosis↗