Evaluation of Nosocomial Infection Control Programs in health services / Avaliação dos Programas de Controle de Infecção Hospitalar em serviços de saúde / Evaluación de los Programas de Control de Infección Hospitalaria en servicios de salud

OBJECTIVES: to evaluate the Nosocomial Infection Control Programs in hospital institutions regarding structure and process indicators. METHOD: this is a descriptive, exploratory and quantitative study conducted in 2013. The study population comprised 13 Nosocomial Infection Control Programs of health services in a Brazilian city of the state of São Paulo. Public domain instruments available in the Manual of Evaluation Indicators of Nosocomial Infection Control Practices were used. RESULTS: The indicators with the highest average compliance were "Evaluation of the Structure of the Nosocomial Infection Control Programs" (75%) and "Evaluation of the Epidemiological Surveillance System of Nosocomial Infection" (82%) and those with the lowest mean compliance scores were "Evaluation of Operational Guidelines" (58.97%) and "Evaluation of Activities of Control and Prevention of Nosocomial Infection" (60.29%). CONCLUSION: The use of indicators identified that, despite having produced knowledge about prevention and control of nosocomial infections, there is still a large gap between the practice and the recommendations. .

OBJETIVOS: avaliar os Programas de Controle de Infecção Hospitalar nas instituições hospitalares, quanto aos indicadores de estrutura e processo. MÉTODO: trata-se de um estudo descritivo, exploratório e quantitativo, realizado em 2013. A população foi composta por 13 Programas de Controle de Infecção Hospitalar de serviços de saúde, de uma cidade brasileira do interior paulista. Foram utilizados instrumentos de domínio público, disponibilizados no Manual de Indicadores de Avaliação de Práticas de Controle de Infecção Hospitalar. RESULTADOS: os indicadores com maior média de conformidade foram "Avaliação da Estrutura dos Programas de Controle de Infecção Hospitalar" (75%) e "Avaliação do Sistema de Vigilância Epidemiológica de Infecção Hospitalar" (82%) e os com menores médias foram "Avaliação das Diretrizes Operacionais" (58,97%) e "Avaliação das Atividades de Controle e Prevenção de Infecção Hospitalar" (60,29%). CONCLUSÃO: o uso de indicadores identificou que, apesar do conhecimento produzido sobre ações de prevenção e controle de infecções hospitalares, ainda existe um grande hiato entre prática e recomendações. .

OBJETIVOS: evaluar los Programas de Control de Infección Hospitalaria en las instituciones hospitalarias respecto a los indicadores de estructura y proceso. MÉTODO: se trata de un estudio descriptivo, exploratorio y cuantitativo, desarrollado en 2013. La población fue compuesta por 13 Programas de Control de Infección Hospitalaria de servicios de salud de una ciudad brasileña del interior paulista. Fueron utilizados instrumentos de dominio público, disponibles en el Manual de Indicadores de Evaluación de Prácticas de Control de Infección Hospitalaria. RESULTADOS: los indicadores con mayor promedio de conformidad fueron "Evaluación de la Estructura de los Programas de Control de Infección Hospitalaria" (75%) y "Evaluación del Sistema de Vigilancia Epidemiológica de Infección Hospitalaria" (82%) y aquellos con menores promedios "Evaluación de las Directivas Operacionales" (58,97%) y "Evaluación de las Actividades de Control y Prevención de Infección Hospitalaria" (60,29%). CONCLUSIÓN: el uso de indicadores posibilitó identificar que, a pesar del conocimiento producido sobre acciones de prevención y control de infecciones hospitalarias, todavía existe un gran hiato entre la práctica y las recomendaciones. .

Cost effectiveness of targeted high-dose atorvastatin therapy following genotype testing in patients with acute coronary syndrome.

BACKGROUND: Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. METHODS: A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. RESULTS: Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. CONCLUSIONS: Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.

Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

BACKGROUND: The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. RESULTS: Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. CONCLUSION: LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

Biomarker assessment of the immunomodulator effect of atorvastatin in stable renal transplant recipients and hypercholesterolemic patients.

BACKGROUND: HMG-CoA reductase inhibitors (statins) have effects beyond lipid lowering, including immunomodulatory and anti-inflammatory properties. Statins are frequently combined with immunosuppressive agents in transplant recipients to modulate the hyperlipidemic side effects of the immunosuppressants. However, the role of statins in the immunosuppressive response that is achieved in individual patients remains to be assessed. OBJECTIVE: The aim of this study was to evaluate the immunomodulatory effect of atorvastatin given alone and in combined treatment with tacrolimus and mycophenolate mofetil. STUDY DESIGN: Two patient groups were studied: renal transplant recipients receiving tacrolimus and mycophenolate mofetil therapy, and hypercholesterolemic patients (the control group). Fasting blood samples were taken from participants before and 1 month after atorvastatin treatment was started to study a small battery of biomarkers that are able to reflect the range of the effects of immunosuppressive therapy and atorvastatin. SETTING: All patients in the study were enrolled at the Hospital Clinic of Barcelona. PATIENTS: All patients enrolled in the study were candidates for treatment with atorvastatin because of high cholesterol levels. One group consisted of 25 stable renal transplant recipients with low-density lipoprotein (LDL) cholesterol levels above 100 mg/dL after 3 months of therapeutic lifestyle changes, according to the guidelines of the National Kidney Foundation - Kidney Disease Outcomes Quality Initiative. The other group included 25 hypercholesterolemic patients with LDL cholesterol levels above target values for the patients' overall risk, as derived from the National Cholesterol Education Program Adult Treatment Panel III criteria. INTERVENTION: Atorvastatin (Lipitor®) treatment was started at a fixed dose of 20 mg daily. MAIN OUTCOME MEASURE: The studied biomarkers were lymphocyte proliferation, intracellular adenosine triphosphate (ATP) synthesis in CD4+ T cells, intralymphocytary cytokine expression (interleukin [IL]-2, interferon [IFN]-γ), soluble cytokine production (IL-2, IFN-γ, IL-10, IL-17, and transforming growth factor-ß) and regulatory T (T(reg)) cells. RESULTS: Atorvastatin proved to be an immunomodulatory agent, significantly decreasing lymphocyte proliferation by 15% (p = 0.001), increasing ATP levels by 16% (p = 0.0004), and showing a trend toward increasing T(reg) cells in hypercholesterolemic patients (p = 0.09). In the renal transplant recipients, atorvastatin therapy did not modify any of the biomarkers of immunosuppression that were studied. CONCLUSION: Atorvastatin showed immunoregulatory effects on T cells in hypercholesterolemic patients. These effects were absent in renal transplant recipients, suggesting that the beneficial effects of atorvastatin in this patient group do not relate to immunoregulation. Therefore, statin treatment cannot be considered as a means to reduce the dose of immunosuppressive agents.

Persistent regional diastolic dysfunction after myocardial ischemia and the effect of statin treatment: assessment with two-dimensional radial strain rate.

BACKGROUND: Persistence of regional diastolic dysfunction after ischemic insult remains debatable. With speckle tracking echocardiography (STE), we sought to (1) prove the persistence of regional diastolic dysfunction, (2) assess the feasibility of applying persistent regional diastolic dysfunction to differentiating ischemic and nonischemic chest pain, and finally (3) examine statin effects on postischemic regional diastolic dysfunction. METHODS: Nineteen patients with variant angina (VA) and 12 normal subjects were enrolled. Comprehensive echocardiographic examinations were performed before and 1 day after coronary angiography (CAG) with ergonovine provocation. Radial systolic (rSRsys) and diastolic (rSRdia) strain rates were obtained and averaged using standard segmentation models corresponding to the three major coronary territories assigned. RESULTS: No significant changes in rSRsys and rSRdia values were observed for controls and in rSRsys for VA. However, rSRdia for VA demonstrated a weak, but significant, decrease from -2.25 +/- 0.71/sec to -2.04 +/- 0.71/sec (P = 0.003) 1 day after CAG. However, because of the wide overlap between rSRdia values in normal and ischemic segments for VA patients, predictability of remote ischemia based solely on the rSRdia was limited. Subgroup analysis according to statin prescription showed that statin administration contributed to the elimination of rSRdia reduction (-2.28 +/- 0.84/sec on pre-CAG vs. -2.29 +/- 0.77/sec on post-CAG, P = 0.72 for patients without statin premedication; -2.23 +/- 0.64/sec for pre-CAG vs. -1.88 +/- 0.65/sec for post-CAG, P = 0.002 for those without). Expectedly, rSRsys values showed no significant changes in all situations. CONCLUSIONS: The presence and sustained nature of regional diastolic dysfunction can be demonstrated with STE. Statin minimized the persistence of regional diastolic dysfunction after an acute ischemia. Although the clinical usefulness of rSRdia by STE appears to be limited, its clinical utility requires further consideration, given the brevity of the ischemia provoked during CAG with ergonovine and the protracted regional diastolic dysfunction.

Assessment of arterial stiffness affected by atorvastatin in coronary artery disease using pulse wave velocity.

PURPOSE: Several studies have shown arterial stiffness changes associated with coronary artery disease (CAD). Recently, statins were reported to improve arterial stiffness. The aim of the study was to evaluate the effect of atorvastatin on arterial stiffness in CAD patients using pulse wave velocity (PWV). METHODS: We evaluated 63 patients with hyperlipemia and CAD. Forty-three patients were given 10mg atorvastatin daily and 20 patients were assigned to a low-fat diet. Carotid-femoral PWV (PWV-CF), carotid-radial PWV (PWV-CR) and carotid-distal PWV (PWV-CD) were measured in all patients. RESULTS: Compared with baseline, PWV-CF, PWV-CR and PWV-CD decreased after therapy in the atorvastatin group (13.22+/-3.39 & 11.85+/-2.87; 11.85+/-2.72 & 10.73+/-2.31; and 11.04+/-1.99 & 10.15+/-1.75, P < 0.05). There was no difference in the control group (13.29+/-2.89 & 13.93+/-2.89; 11.52+/-2.25 & 12.31+/-2.22; and 10.46+/-1.86 & 11.15+/-1.85, P > 0.05). After treatment, values of total cholesterol, triglyceride and low density lipoprotein (LDL) cholesterol were reduced in the 2 groups (P < 0.05). CONCLUSIONS: The study demonstrated that atorvastatin can improve arterial stiffness in CAD patients independent of its lipid-lowering properties.

Medicinal chemistry strategies in follow-on drug discovery.

Drug discovery targeting novel mechanisms has become extremely expensive and risky. The annual first-in-class drug approvals have not been satisfactory in the past decade (two to six per year) despite an increased R&D budget. Follow-on programs targeting proven mechanisms are less risky and costly but can produce drugs with meaningful differentiations and thus can play an important supporting role. This article will discuss the medicinal chemistry strategies that have been utilized by the pharmaceutical industry to exploit validated therapeutic targets.

Coadministration of dabigatran etexilate and atorvastatin: assessment of potential impact on pharmacokinetics and pharmacodynamics.

BACKGROUND: Dabigatran etexilate, a novel oral direct thrombin inhibitor, has been approved for prophylaxis of thromboembolism in patients undergoing total knee or total hip replacement, and is under clinical investigation for treatment of venous thromboembolism, prevention of stroke in patients with atrial fibrillation, and the treatment of thromboembolic complications following acute coronary syndromes. OBJECTIVE: To evaluate the potential impact of atorvastatin coadministration on the pharmacokinetics, pharmacodynamics, and safety of dabigatran etexilate. METHODS: Healthy male and female volunteers (n = 22) were recruited to this open, randomized, multiple-dose, three-way crossover study. They received dabigatran etexilate 150 mg twice daily on days 1-3 and once daily on day 4, atorvastatin 80 mg once daily on days 1-4, or both treatments together on days 1-4. RESULTS: Exposure to dabigatran at steady state (area under the drug plasma concentration-time curve at steady state) was reduced by 18% with concomitant atorvastatin administration. An 18% increase in plasma atorvastatin concentration occurred with coadministration of dabigatran etexilate. Exposure to its metabolite 2'-hydroxy-atorvastatin remained essentially unchanged and exposure to 4'-hydroxy-atorvastatin was increased by 15%. The small changes observed are deemed of little clinical relevance given the overall inter-individual variability in the metabolism of atorvastatin. Furthermore, there were no changes in the concentrations of active HMG-CoA reductase inhibitors in plasma following dabigatran etexilate coadministration. Six subjects in the atorvastatin treatment group, six subjects during combination treatment, and eight subjects in the dabigatran treatment group reported adverse events. Most of the adverse events reported were nervous system disorders such as dizziness and headache, and general disorders such as fatigue. All adverse events were resolved at the end of the study. CONCLUSION: Results of this randomized, open-label, three-way crossover design study in healthy male and female volunteers showed that atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of dabigatran, and vice versa, dabigatran etexilate had no impact on the pharmacokinetic/pharmacodynamic profile of atorvastatin. Both drugs were well tolerated when given alone or in combination.

Assessment of regional systolic and diastolic functions affected by atorvastatin in coronary artery disease using tissue Doppler imaging.

BACKGROUND: Several studies have shown regional left ventricular (LV) systolic and diastolic changes associated with coronary artery disease (CAD). Statins may have beneficial pleiotropic effects in addition to their lipid-lowering properties. HYPOTHESIS: We hypothesized that atorvastatin can improve regional LV systolic and diastolic functions in CAD patients using tissue Doppler imaging (TDI). METHODS: A total of 63 patients with hyperlipemia and CAD were studied. Forty-three patients were given 10 mg daily of atorvastatin and 20 patients were assigned only a low-fat diet. Tissue Doppler imaging was applied to evaluate LV peak systolic velocity (VS), early diastolic velocity (VE), and late diastolic velocity (VA) in 18 segments. The mean value of LV peak systolic velocity (VS(')), the mean value of early diastolic velocity (VE(')), and the mean value of late diastolic velocity (VA(')), in 18 segments were calculated. RESULTS: Compared with the baseline, VS('), and VE('), increased significantly after the therapy in the atorvastatin group (p < 0.05), while there was no change in the control group (p > 0.05). At 6 mo of therapy, a significant reduction in total cholesterol, triglyceride, and low-density lipoprotein (LDL) cholesterol was observed in the 2 groups (p < 0.05). CONCLUSIONS: These findings demonstrate that atorvastatin can improve regional LV systolic and diastolic functions in CAD patients independent of its lipid-lowering properties.

Effect of atorvastatin on energy expenditure and skeletal muscle oxidative metabolism at rest and during exercise.

Statins are associated with adverse effects in skeletal muscle. This study tested the hypothesis that atorvastatin would increase the respiratory exchange ratio (RER) at rest and during exercise. Twenty-eight healthy subjects (mean age 52 years) were enrolled in a double-blind, placebo-controlled, randomized study of the effects of atorvastatin (40 mg/day) on whole body energetics over 8 weeks. Ventilatory gas exchange measurements, at rest and during bicycle ergometry, were used to assess muscle oxidative metabolism. Thirteen subjects from each treatment arm completed the study. Eight weeks of atorvastatin lowered plasma low-density lipoprotein cholesterol concentration but had no effect on resting or submaximal energy expenditure, RER, or calculated fatty acid oxidation rates. Atorvastatin did not affect maximal exercise oxygen consumption or the anaerobic threshold. Eight weeks of atorvastatin therapy was not associated with alterations in substrate oxidation, or muscle oxidative function at rest, or during exercise in healthy adults.

A dose-specific meta-analysis of lipid changes in randomized controlled trials of atorvastatin and simvastatin.

BACKGROUND: The available statins exhibit differences in the potency with which they alter serum lipid levels. OBJECTIVE: Meta-analyses were conducted to assess the relative potency of atorvastatin and simvastatin (the 2 most commonly prescribed statins) across all possible dose combinations in terms of changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, National Health Service (NHS) Centre for Reviews and Dissemination database, NHS Economic Evaluation Database, and Database of Abstracts of Reviews of Effects were searched for randomized, head-to-head trials of atorvastatin and simvastatin in patients aged >or=18 years with elevated levels of serum TC and LDL-C. Reference lists of the identified articles, letters, and editorials also were reviewed. The manufacturers of atorvastatin and simvastatin products were contacted for relevant unpublished data. All studies were reviewed and rated for quality by 2 independent reviewers. The maximum quality score was 4 points; trials with a score of <2 points were considered to be of poor quality and were excluded from analysis. Dose comparisons were abstracted in pairs from each trial. Meta-analyses were conducted on the fixed-dose pairs for each lipid parameter. Weighted mean differences in the change in TC, LDL-C, TG, and HDL-C were estimated using the Der Simonian and Laird random-effects model. RESULTS: Seventeen published trials and 1 unpublished study were included in the meta-analyses. Atorvastatin treatment was associated with significantly greater reductions in TC, LDL-C, and TG in the majority of dose comparisons with simvastatin. The potency of atorvastatin and simvastatin was comparable at dose ratios between 1:2 and 1:4. Higher doses of simvastatin were more effective in increasing HDL-C levels than atorvastatin, with no apparent dose-equivalence point. The HDL-C advantage of simvastatin was greatest when simvastatin 80 mg was compared with atorvastatin 80 mg (weighted mean difference, -4.35%; 95% CI, -5.64 to -3.08, P < 0.001). CONCLUSIONS: In these meta-analyses, atorvastatin was 2 to 4 times as potent as simvastatin in reducing TC, LDL-C, and TG, indicating that the dose equivalence of atorvastatin and simvastatin lay between 1:2 and 1:4. In contrast, simvastatin was more effective than atorvastatin in increasing HDL-C, but without any indication of a point of dose equivalence.

Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS).

AIMS/HYPOTHESIS: We estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS). SUBJECTS AND METHODS: A total of 2,838 patients, who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol, were recruited from 32 centres in the UK and Ireland and randomly allocated to atorvastatin 10 mg daily (n = 1,428) or placebo (n = 1,410). These subjects were followed-up for a median period of 3.9 years. Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint, and of cost per life-year gained and cost per quality-adjusted life-year (QALY) gained over a patient's lifetime. RESULTS: Over the trial period, the incremental cost-effectiveness ratio (ICER) was estimated to be 7,608 pounds per year free of any CARDS primary endpoint; the ICER was calculated to be 4,896 pounds per year free of any cardiovascular endpoint and 4,120 pounds per year free of any study endpoint. Over lifetime, the incremental cost per life-year gained was 5,107 pounds and the cost per QALY was 6,471 pounds (costs and benefits both discounted at 3.5%). CONCLUSIONS/INTERPRETATION: Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes, with the ICER for this intervention falling within the current acceptance threshold ( 20,000 pounds per QALY) specified by the National Institute for Health and Clinical Excellence (NICE).

Evaluation of apoptosis and necrosis induced by statins using fluorescence-enhanced flow cytometry.

The purpose of this study was to evaluate the apoptosis and necrosis induced by five kinds of statins in IM-9 human lymphoblasts with fluorescence-enhanced flow cytometry using avidin-biotin complex. IM-9 human lymphoblasts (2 x 10(4) cells/cm2) were seeded into tissue culture plates and incubated with five kinds of statins. Statin-treated cells were first incubated with biotin-annexin V, followed by addition of avidin-FITC and propidium iodide, and then subjected to flow cytometry. The fluorescence intensity was enhanced using an avidin-biotin complex system, resulting in successful separate determination of the statin-induced apoptosis and necrosis by flow cytometry, which enabled us to quantitatively evaluate the statin-induced cell damage. Flow cytometric analysis results in the intensity of statin-induced apoptosis in IM-9 cells as follows: atorvastatin cerivastatin>fluvastatin simvastatin>pravastatin. The intensity of statin-induced necrosis in IM-9 cells was expressed as follows: atorvastatin cerivastatin>fluvastatin simvastatin>pravastatin. The total damage of IM-9 cells induced by five kinds of statins were expressed as the sum of both percentages of apoptosis and necrosis as follows: atorvastatin cerivastatin>fluvastatin simvastatin>pravastatin. Our studies show that fluorescence enhancement with avidin-biotin complex is useful for the identification and quantitation of annexin-positive apoptosis cells and thus, the fluorescence-enhanced flow cytometry was shown to be applicable for screening of statins as new anti-leukemia agents.

[Noninvasive assessment of the effect of atorvastatin on coronary microvasculature and endothelial function in patients with dyslipidemia]. / Determinación no invasiva del efecto de atorvastatina en la microvasculatura coronaria y la función endotelial periférica de pacientes dislipémicos.

INTRODUCTION AND OBJECTIVES: The effect of statins has been monitored mainly in peripheral arteries. It is now possible to study coronary microcirculation by analyzing coronary reserve with transthoracic echocardiography. The aim of this study was to use this noninvasive technique to evaluate the effect of atorvastatin on peripheral endothelial function and on the coronary microvasculature in patients with dyslipidemia. PATIENTS AND METHOD: We included 21 patients with dyslipidemia but no clinical antecedents of atherosclerosis. Mean (SD) age was 64.9 (11) years, and women made up 61.9% of the group. All patients were treated with 20 mg atorvastatin during 3 months. Lipid profile, carotid intima-media thickness, endothelium-dependent vasodilation and coronary flow reserve were determined at baseline and at the end of treatment. All studies were performed with echocardiographic techniques. RESULTS: Together with improvements in the lipid profile, we found a 43% increase in endothelium-dependent vasodilation (4.3 [4.4] to 6.2 [3.8]; P=.07) and a 25% increase in coronary flow reserve (2.5 [0.6] vs 3.1 [0.8]; P=.002). The increase in endothelium-dependent vasodilatation correlated with age (r=-0.60; P=.004), intima-media thickness (r=-0.47; P=.029), low-density lipoprotein level before treatment (r=-0.43; P=.05), and baseline endothelium-dependent vasodilatation (r=-0.63; P=.002). The increase in coronary flow reserve correlated with low-density lipoprotein level after treatment (r=-0.51; P=.04). CONCLUSIONS: Short-term treatment with atorvastatin improved the lipid profile, coronary microvascular function and endothelium-dependent vasodilation in the peripheral circulation. The noninvasive assessment of coronary reserve is feasible with transthoracic echocardiography.

Effect of tablet splitting on serum cholesterol concentrations.

OBJECTIVE: To evaluate the effects of tablet splitting on low-density lipoprotein (LDL) cholesterol and total cholesterol values in patients taking simvastatin and atorvastatin. DESIGN: A retrospective chart review of total cholesterol and LDL cholesterol values of patients instructed to split simvastatin or atorvastatin between January 1999 and November 2000. SETTING: Veterans Affairs Medical Center in Huntington, WV. PATIENTS: Patients were included if they were taking simvastatin or atorvastatin with regular lipid management and follow-up laboratory results. Patients were required to remain on the same milligram-per-day dose at least 6-8 weeks before and after tablet-splitting initiation and have cholesterol values drawn at least 6 weeks after initiation of both whole-tablet and half-tablet dosing. Patients were excluded if they had a triglyceride level > 400 mg/dL or were noncompliant on the basis of pharmacy records and provider notes. MEASUREMENT OUTCOMES: The primary end points were changes in total cholesterol and LDL cholesterol values before and after the patient was switched to half-tablet therapy. RESULTS: The overall results for this review demonstrated no statistically significant increase in total cholesterol and LDL cholesterol concentrations. Total cholesterol and LDL cholesterol values actually decreased from presplitting to postsplitting, p = 0.017 and p = 0.003, respectively. CONCLUSIONS: The investigation showed that half-tablet dosing was as effective as whole-tablet dosing. The program will be continued as a part of quality patient care at the Huntington Veterans Affairs Medical Center.

Atorvastatin.

Atorvastatin (Lipitor, Pfizer) is a safe and effective 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor (statin). It is the most potent currently available statin in terms of lowering low-density lipoprotein (LDL) and total cholesterol levels. It was the first statin shown to lower triglycerides in patients with isolated hypertriglyceridaemia. It has a good safety profile. In common with other statins, it has non-lipid-lowering effects including improving endothelial function, antiproliferative actions on smooth muscle and reducing platelet aggregation. It also has anti-inflammatory effects and may reduce plasma glucose levels. Clinical trial evidence with this statin is currently limited. It did slightly reduce events in the AVERT trial comparing patients receiving coronary angioplasty with those receiving high-dose atorvastatin therapy and in the MIRACL study reduced ischemia in patients with acute coronary syndromes. Other end point trials are in progress.