Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 55 records · Page 3Linked to original sources

PubMed2004

[Clinical study of the month. REVERAL and PROVE-IT: confirmation of the concept " the lower, the better" for cholesterol therapy in patients with coronary heart disease].

Statins, as compared to placebo, have proven their efficacy in reducing cardiovascular events in patients with or without cardiovascular disease and in a large range of cholesterol levels. Two new head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day were recently completed. The mechanistic "Reversing Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial randomised 502 patients with stable coronary disease. Atorvastatin 80 mg (leading to a mean LDL cholesterol of 79 mg/dl) was superior to pravastatin 40 mg (mean LDL of 110 mg/dl) in terms of limiting the progression of atheroma assessed with the use of intravascular ultrasonography after 18 months of follow up (p = 0.02). These differences may be related to the greater reduction in atherogenic lipoprotein (-46% versus -26%, p < 0.001) and C-reactive protein (-36% versus -5%, p < 0.001) in patients treated with atorvastatin as compared to pravastatin. In the clinical "Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial, 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months. Again, atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower risk of the primary end point, a composite of major cardiovascular events (p = 0.005). Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation. What so ever, the results suggest that the target LDL cholesterol level may be lower than recommended in the current guidelines in high-risk patient so that a sea change in the prevention and management of atherosclerotic vascular disease may occur very soon.

Anticholesteremic Agents↗

PubMed2004

[Reactive hypoglycaemia, a mysterious, insidious but non dangerous critical phenomenon].

Numerous individuals complain of malaise attributed to hypoglycaemia. However, the diagnosis of hypoglycaemia is rarely documented and most often overstated. Reactive hypoglycaemia in the postprandial state is rather exceptional. The diagnosis relies upon the measurement of plasma glucose concentration (< 3 mmol/l or 55 mg/dl) at the time of the malaise. Reactive hypoglycaemia is generally associated with adrenergic symptoms and, less often, with cognitive disturbances. Importantly, a plasma glucose concentration below 3 mmol/l during an oral glucose tolerance test is not sufficient to decide that the patient suffers from reactive hypoglycaemia. Treatment is based on dietary advices including frequent small split meals and limitation of carbohydrates with high glycaemic index. Acarbose, a specific inhibitor of gut alpha-glucosidase enzymes, may be helpful in case of diet failure. As compared with true reactive hypoglycaemia, a postprandial hyperadrenergic reaction without real concomitant hypoglycaemia is much more prevalent. Careful anamnesis may suspect such a diagnosis, but other diagnoses such as panic attack or vasovagal reaction should be excluded. Treatment is purely symptomatic and essentially empiric.

Acarbose↗

PubMed2004

[Ezetimibe (Ezetrol)].

Ezetimibe (Ezetrol), recently launched in Belgium by Merck Sharp& Dohme and Schering Plough, is presented as 10 mg tablets. It belongs to a new class of lipid-lowering agents that selectively inhibit the intestinal absorption of cholesterol and phytosterols. Its mechanism of action results in a synergistic cholesterol-lowering effect together with a statin that inhibits cholesterol synthesis by the liver. Ezetimibe, at a daily dose of 10 mg, is indicated, in combination with a statin, as adjuvant treatment to diet in patients with primary hypercholesterolaemia (homozygote or heterozygote familial form and non-familial polygenic form) not well controlled with a statin alone. In case of statin contra-indication or intolerance, ezetimibe can be used in monotherapy. Its tolerance profile is excellent. Statin-ezetimibe combination allows to significantly reduce total and LDL cholesterol levels and increases the percentage of hypercholesterolaemic patients who will reach the target levels recommended in the international guidelines against atherosclerosis. However, such a combination should still prove its efficacy in reducing cardiovascular morbidity and mortality in large prospective clinical trials.

Anticholesteremic Agents↗

PubMed2004

[Valdecoxib (Bextra)].

Valdecoxib (Bextra tablets of 10 mg and 20 mg) is a new non steroidal antiinflammatory drug (NSAID) that selectively inhibits COX-2 isoform of cyclo-oxygenase. It is indicated for the symptomatic treatment of osteoarthritis or rheumatoid arthritis (10 to 20 mg once a day) and for the treatment of primary dysmenorrhea (40 mg once a day). Valdecoxib is as efficacious as conventional non-COX-2 selective NSAIDs, but offers the advantage of a much better gastrointestinal tolerance. Valdecoxib has a prodrug that can be administered intravenously or intramuscularly (parecoxib, Dynastat) and has been developed for the short-term treatment of postsurgical pain.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Management of the metabolic syndrome.

The metabolic syndrome (MetS) is strongly associated with insulin resistance and consists of a constellation of factors that raise the risk for cardiovascular diseases and diabetes mellitus. Therefore, the primary goals of treating MetS are prevention of type 2 diabetes and cardiovascular events. Three levels of intervention may be considered for individuals with MetS : 1) management of underlying risk conditions by controlling weight excess, enhancing regular physical exercise and promoting healthy diet; 2) management of individual risk factors such as dyslipidaemia, hypertension, hyperglycaemia and prothrombotic state; and 3) targeting insulin resistance by using specific insulin sensitizers such as thiazolidinediones. The most important therapeutic intervention effective in subjects with MetS should focus on modest weight reduction and regular leisure-time physical activities. Although lifestyle modification is the first-line therapy, drug therapy may be necessary in many patients to achieve recommended goals regarding lipid profile, blood pressure and blood glucose control. Rather than to use a magic bullet that might fully reverse the underlying cause of the syndrome, one appealing alternative would be to use a so-called "polypill" targeting each of the components of MetS. However, such a polypill should ideally contain numerous molecules that all have shown a potential interest for the management of MetS such as metformin, acarbose, a thiazolidinedione, a statin, a fibrate, an inhibitor of the renin-angiotensin system, aspirin. The growing prevalence and high-risk nature of MetS highlights the need to identify individuals with this condition and to treat them with an aggressive multitargeted approach.

Blood Glucose↗

PubMed2004

[Hypoglycaemic coma, a feared paroxysmal phenomenon in type 1 diabetic patient].

The hypoglycaemic coma is a severe complication for type 1 diabetic patients. Rarely fatal it may be associated with various paroxysmal accidents, potentially harmful, especially during driving. Hypoglycaemia certainly alters the quality of life because it markedly increases the anxiety of both the patient and his/her family. It is considered as a major limiting factor in the glycaemic management of type 1 diabetic patients. Being the consequence of numerous causal factors, hypoglycaemic coma is not always easy to prevent and may occur as a paroxysmal phenomenon, sometimes without obvious contributing circumstances. After having defined the various hypoglycaemic thresholds, we will analyse the pathophysiology of insulin-induced hypoglycaemia and of its hormonal counterregulation, and we will describe the hypoglycaemia unawareness phenomenon. These elements should help to better understand why a hypoglycaemic coma may suddenly occur in a diabetic patient. Some advices will also be given to reduce the risk of such a paroxysmal complication in patients with type 1 diabetes.

Diabetes Mellitus, Type 1↗

PubMed2004

[Porphyrias, a rare cause of acute abdominal pain].

The porphyrias are uncommon disorders caused by deficiencies of some enzymes of the heme biosynthetic pathway. Only four hepatic porphyrias are able to cause acute abdominal syndrome. In any case, the diagnosis requires the demonstration of increased urinary or stool excretion of accumulated metabolites of heme synthesis. Treatment is now possible and is able to reduce the burden of these metabolic diseases. The management implies also the identification of trigger exogenous factors such as oral contraceptives.

Abdominal Pain↗

PubMed2004

[New advances in drug therapy in 2003-2004].

The most important drugs registered and/or launched in Belgium during the last year in the various disciplines of internal medicine will be briefly described. The main characteristics of each molecule and its modalities of appropriate use in clinical practice will be emphasized. Both the efficacy and safety of these new drugs have been evaluated in randomised controlled trials according to the evidence-based-medicine criteria. Most of them are currently studied in order to further demonstrate their potential benefit on a long-term basis, in large cohort of patients and using hard clinical endpoints.

Asthma↗

PubMed2004

[Optimizing the managment of patients with diabetes mellitus: selected clinical trials from the 2004 Congress of the American Diabetes Association].

The 64th scientific congress of the American Diabetes Association had a special session devoted to the presentation of the results from three clinical trials: 1) the first multicentre international trial of pancreatic islet transplantation according to the so-called Edmonton protocol with the primary endpoint of restoring insulin independence in type 1 diabetic patients; 2) three pivotal studies of 30 weeks testing both the efficacy and safety of exenatide (exendin-4), a new insulin secretagogue that is a long-acting analogue of glucagon-like peptide-1, in patients with type 2 diabetes treated with either metformin, or a sulfonylurea, or a metformin-sulfonylurea combination; and 3) the "Collaborative AtoRvastatin Diabetes Study" (CARDS), a placebo-controlled primary prevention trial of cardiovascular complications using atorvastatin 10 mg in 2 838 at risk patients with type 2 diabetes. The main results and conclusions of these trials are briefly presented as they open new perspectives in the management of patients with type 1 or type 2 diabetes mellitus.

Anticholesteremic Agents↗

PubMed2004

[Effects of intensive insulin therapy after an acute myocardial infarction in patients with type 2 diabetes: results of the DIGAMI-2 trial].

The results of DIGAMI-2 (< >) trial were presented at the 40th scientific congress of the European Association for the Study of Diabetes (EASD) in Munich on September 6, 2004. The main objective of this multicentre international trial was to confirm the positive results of the first DIGAMI trial published in 1995--1997. This pilot trial demonstrated that insulin-glucose infusion followed by a subcutaneous multidose insulin regimen reduces total mortality after 1 and 3 years in diabetic patients with acute myocardial infarction. DIGAMI-2, by comparing three groups of subjects receiving various interventions, aimed at determining the relative benefit resulting from the insulin-glucose infusion in the acute phase and that attributable to long-term intensive insulin therapy in a similar population of type 2 diabetic patients. No significant difference was observed between the three groups as far as total mortality and cardiovascular morbidity were concerned. These negative results may be explained by the absence of significant difference in blood glucose control between the three groups, by the fact that glycaemic targets were not reached in the intensive group and, last but not least, by a better management of other risk factors, allowing already markedly reduced cardiovascular morbidity and mortality in the reference group treated with conventional antidiabetic therapy. In conclusion, DIGAMI-2 argues for a multidisciplinary management of diabetic patients to reach strict glycaemic targets with an intensive insulin scheme and confirms the remarkable advances in cardiovascular protection thanks to an optimised global pharmacological approach combined with modern revascularisation procedures.

Clinical Trials as Topic↗

PubMed2004

[Withdrawal of rofecoxib (Vioxx): what about cardiovascular safety of COX-2 selective non-steroidal anti-inflammatory drugs?].

Rofecoxib (Vioxx), the first COX-2 selective non-steroidal anti-inflammatory drug (NSAID), was recently withdrawn by Merck Sharp & Dohme. Indeed, both observational studies and randomised clinical trials showed that rofecoxib is associated with a significantly increased risk of acute myocardial infarction in patients receiving either high daily dosage (>25 mg/day) or for a long period of time (> 18 months). The precise mechanism responsible for this phenomenon still remains unknown. Currently available data suggest that this adverse effect is not observed with other COX-2 NSAIDs, especially celecoxib for which the information is most abundant. Nevertheless, caution is required because of lack of prospective long-term data, and strict respect of indications and modalities of clinical use of COX-2 NSAIDs is mandatory. Finally, in patients with high cardiovascular risk who should receive a COX-2 selective NSAID, the association with a low dose of acetylsalicylic acid is recommended in order to benefit of a protective antiplatelet effect.

Cardiovascular Diseases↗

PubMed2004

[Percutaneous transluminal coronary angioplasty (PTCA) in diabetic patients. Part 1: failure due to restenosis after simple PTCA].

Diabetes mellitus, essentially type 2 diabetes, is markedly associated with a high risk of cardiovascular diseases, especially coronary artery disease (CAD). Revascularization techniques, first coronary artery bypass graft (CABG) and second percutaneous transluminal coronary angioplasty (PTCA), have drastically changed the management of patients with CAD. Unfortunately, overall results of such revascularization procedures are less impressive in diabetic patients than in nondiabetic subjects, because of a worse vascular bed due to a more diffuse disease including small vessels. The diabetic population is indeed characterized by higher rates of both post-CABG thrombosis and post-PTCA restenosis, as compared to the corresponding rates observed in a nondiabetic population. Such vascular complications result in a higher incidence of coronary events leading to greater morbidity and mortality in both the short (weeks-months) and long (years) term. The bad quality of blood glucose control appears to play a crucial role in the risk of restenosis and further complications. The use of endovascular stents, especially new drug-eluting stents reducing the risk of restenosis, may represent a new opportunity for the management of a high-risk population such as diabetic patients.

Angioplasty↗

PubMed2004

[The drug of the month: Olmesartan medoxomil].

Olmesartan medoxomil (Belsar, Olmetec) developed by Sankyo Pharma and proposed by Sankyo Pharma but also Menarini is a new angiotensin II ATI receptor blocker. Its indication is the treatment of hypertension. Olmesartan is indeed an antihypertensive agent with an efficacy dependent on the dose from 10 to 40 mg. It is taken once a day, because of a long duration of action. This prodrug has a dual elimination pathway (biliary and renal). The contraindications are the same as for the other sartans. One of its main advantage, besides its rapidly observed efficacy to lower high blood pressure, is its relatively low cost within this family. It has also cardiovascular and renal protective effects. The recommended usual dosage is 20 mg/day.

Antihypertensive Agents↗

PubMed2004

[Percutaneous coronary angioplasty in diabetic patients. Part II: hopes based on endovascular prosthesis].

Coronary artery revascularization procedures provide less favourable results in diabetic patients than in non-diabetic individuals. Especially, percutaneous coronary angioplasty (PTCA) is associated with a higher rate of restenosis and recurrence of cardiac morbidity and death. In diabetic patients, PTCA should, if possible, be combined with a stent. Bare-stents allow to reduce approximately by half the risk of restenosis, but unfortunately their efficacy decreases as the vessel diameter decreases, a common finding among diabetic patients with angiopathy. ARTS ("Arterial Revascularization Therapy Study") recently showed that diabetic patients have a worse prognosis even when bare-stents are combined with PTCA as compared to non-diabetic subjects and as compared to diabetic patients treated with coronary artery bypass graft. These results open new perspectives in favour of the use of drug-eluting stents containing pharmacological agents capable of preventing restenosis. Such new stents might improve the management of diabetic patients with coronary heart disease.

Angioplasty, Balloon, Coronary↗

PubMed2004

[Interheart: nine risk factors predict nine out of ten myocardial infarctions].

INTERHEART is a standardised case-control study of acute myocardial infarction in 52 countries representing every inhabited continent. 15152 cases and 14820 controls were enrolled. Collectively, 9 factors accounted for 90% of myocardial infarctions in men and 94% in women. These factors were 6 risk factors (dyslipidaemia characterized by high apoB/apoA1 ratio, smoking, hypertension, diabetes mellitus, abdominal obesity and stressful psychosocial factors) and 3 protective factors (daily consumption of fruits and vegetables, regular alcohol consumption, and regular physical activity). These findings suggest that interventions targeting these 9 factors have the potential to prevent most premature cases of myocardial infarction and that these strategies should be implemented worldwide.

Case-Control Studies↗

PubMed2004

[Percutaneous coronary angioplasty in diabetic patients: new prospects with drug-eluting stents].

Coronary revascularization procedures are associated with less favourable outcomes in diabetic patients as compared to non-diabetic individuals. Especially, percutaneous coronary angioplasty (PTCA) is associated with a high level of restenosis and recurrent cardiac morbidity and mortality. In diabetic patients, PTCA should ideally be combined with stents. Bare-metal stents reduce by almost half the risk of restenosis, but this favourable effect decreases with the vessel calibre, a common finding in diabetic patients. Drug-eluting stents containing pharmacological agents that can reduce the risk of restenosis (sirolimus, paclitaxel) provide better angiographic results, including in small coronary arteries, and this effect has been shown to be accompanied by significant reduction of both morbidity and mortality. Such preliminary results obtained in the general population (including around 20% of diabetic subjects) deserve further confirmation in a large clinical trial specifically devoted to diabetic patients. Drug-eluting stents may represent a major advance in the management of diabetic patients with coronary heart disease in the near future.

Angioplasty, Balloon, Coronary↗

PubMed2003

[How I explore...the secrets of a meta-analysis].

Meta-analysis is becoming a key partner of Evidence-Based Medicine. This statistical tool is currently used in most systematic reviews and allows to quantitatively synthesize the results of several studies by a single weighted average whose precision is indicated by the confidence interval. A standardized graphical representation allows, at first glance, to derive a lot of useful information, especially the number of studies taken into account for the analysis, the mean effect observed in each study with its confidence interval, the relative size (number of subjects) of each study, the homogeneity/heterogeneity of between-study results, finally the overall mean effects with its confidence interval. The meta-analysis plays a key-role in epidemiology, for the evaluation of a risk or a protective factor, and in therapeutics, for summarizing the results of numerous clinical trials with a specific drug or a pharmacological class in a given disease.

Evidence-Based Medicine↗

PubMed2003

[Clinical study of the month. Which initial antihypertensive? Results from the ALLHAT trial].

Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is still controversial. The "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" (ALLHAT) should give such an answer. It is a randomised, double-blind, trial designed to determine whether treatment with either a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. A total of 33,357 participants aged 55 years or older with mild to moderate hypertension and at least 1 other CHD risk factor were randomly assigned to receive chlorthalidone (12.5 to 25 mg/day; n = 15,255), amlodipine (2.5 to 10 mg/day; n = 9,048) or lisinopril (10 to 40 mg; n = 9,054). The primary outcome combined both fatal CHD and non-fatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-causes mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure and peripheral arterial disease). Chlorthalidone was slightly more effective in reducing systolic pressure while amlodipine reduced slightly more effectively diastolic blood pressure. After a mean follow up of 4.9 years, no differences were observed between the three treatments regarding both the primary outcome and the total mortality. Secondary outcomes were similar when comparing amlodipine vs chlorthalidone. A moderately higher 6-year incidence rate of clinically detected heart failure was observed with amlodipine, but without significant influence on mortality. For lisinopril vs chlorthalidone, lisinopril had slightly higher 6-year rates of combined CVD, stroke and heart failure. In conclusion, thiazide-type diuretics are superior in preventing one or more major forms of CVD and offer the advantage to be cheaper. They should be preferred for first-step antihypertensive therapy. However, to reach the recommended blood pressure target, most patients should receive a combination of antihypertensive compounds. Such a combination should always comprise a diuretic agent, in absence of contra-indications.

Antihypertensive Agents↗