Betabloqueantes en diabéticos

Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control; Wai B, Kearney LG, Hare DL, Ord M, Burrell LM, Srivastava PM; Cardiovascular Diabetology 11 (1), 14 (Feb 2012)

ABSTRACT: The prognostic benefits of beta-blockers (BB) in patients with systolic heart failure (SHF) are known but despite this, in patients with diabetes they are underutilized. The aim of this study was to assess the effect of beta-blockers (BB) on glycaemic control in patients with Type 2 Diabetes (T2DM) and systolic heart failure (SHF) stratified to beta-1 selective (Bisoprolol) vs. nonselective BB (Carvedilol). METHODS: This observational, cohort study was conducted in patients with T2DM and SHF attending an Australian tertiary teaching hospital's heart failure services. The primary endpoint was glycaemic control measured by glycosylated haemoglobin (HbA1c) at initiation and top dose of BB. Secondary endpoints included microalbuminuria, changes in lipid profile and estimated glomerular filtration rate (eGFR). RESULTS: 125 patients were assessed. Both groups were well matched for gender, NYHA class and use of guideline validated heart failure and diabetic medications. The mean treatment duration was 1.9 +/- 1.1 years with carvedilol and 1.4 +/- 1.0 years with bisoprolol (p = ns). The carvedilol group achieved a reduction in HbA1c (7.8 +/- 0.21% to 7.3 +/- 0.17%, p = 0.02) whereas the bisoprolol group showed no change in HbA1c (7.0 +/- 0.20% to 6.9 +/- 0.23%, p = 0.92). There was no significant difference in the change in HbA1c from baseline to peak BB dose in the carvedilol group compared to the bisoprolol group. There was a similar deterioration in eGFR, but no significant changes in lipid profile or microalbuminuria in both groups (p = ns). CONCLUSION: BB use did not worsen glycaemic control, lipid profile or albuminuria status in subjects with SHF and T2DM. Carvedilol significantly improved glycemic control in subjects with SHF and T2DM and this improvement was non significantly better than that obtained with bisoprolol. BB's should not be withheld from patients with T2DM and SHF.

Dolor,disconfort toracico en el IM Diferente entre mujeres y hombres

DGNews
Chest Pains Are Less Common in Women After Myocardial Infarction

CHICAGO -- February 21, 2012 -- Women are more likely than men to present to a hospital without chest pain and also have a higher rate of in-hospital death following a myocardial infarction (MI) than men within the same age group, although these differences decrease with increasing age, according to a study published in the February 22/29 issue of JAMA.

“Optimal recognition and timely management of myocardial infarction, especially for reducing patient delay in seeking acute medical care, is critical,” the authors wrote. “The presence of chest pain/discomfort is the hallmark symptom of MI.” Despite this well-accepted symptom, previous analyses have shown that a large number of patients with MI lack chest pain/discomfort at presentation.

“Patients without chest pain/discomfort tend to present later, are treated less aggressively, and have almost twice the short-term mortality compared with those presenting with more typical symptoms of MI,” according to the authors.

They added that women are generally older than men at hospitalisation for MI. “It is plausible that women’s older age at presentation is related to whether they present with chest pain, as well as subsequent hospital mortality. However, a limited number of studies have taken age into account in examining sex differences in MI clinical presentation.”

John G. Canto, MD, Watson Clinic and Lakeland Regional Medical Center, Lakeland, Florida, and colleagues examined the relationship between sex, symptoms when presenting to the hospital, and the risk of death while in the hospital, before and after accounting for age in patients hospitalised with MI.

The study consisted of an analysis of data from the National Registry of Myocardial Infarction (1994-2006) of 1,143,513 registry patients. Of these, 42.1% were women. Women with MI were significantly older than men at hospital presentation, with an average age of 74 years versus 67 years for men.

The overall proportion of patients with MI who presented without chest pain/discomfort was 35.4% and was significantly higher for women than men (42.0% vs 30.7%). Age-specific and further analyses indicated a significant interaction between age and sex, with sex-specific differences in MI presentation without chest discomfort becoming progressively smaller with advancing age.

The in-hospital mortality rate was 14.6% for women and 10.3% for men. The researchers found that in the fully adjusted models, younger women presenting without chest pain/discomfort had greater hospital case-fatality rates than men, a trend that reversed with increasing age. “However, younger women presenting with chest pain/discomfort had a greater hospital case-fatality rate than men with chest pain/discomfort in the same age group, but differences in hospital death rates between men and women decreased with advancing age,” the authors wrote. “These data suggest that the absence of chest pain may be a more important predictor of death in younger women with MI compared with other similarly aged groups.”

The authors added that further research is needed to improve the current understanding of underlying pathophysiology and potentially sex-tailored health messages to the general public and health care providers to encourage men and women with signs and symptoms of acute coronary syndromes to seek care promptly, which will result in improvement in the care and survival of women.

“Our results of sex-based differences in MI symptom presentation in younger patients are provocative and should be confirmed by others with clinical databases of MI or acute coronary syndromes,” the authors wrote. “From a public health perspective, it is appropriate to target high-risk groups for delay (young women) with information on the American Heart Association/National Institutes of Health heart attack message, but until additional research is conducted, the current chest pain/discomfort heart attack symptom message, which targets women and men equally irrespective of age, should remain unchanged.”

BNP es recomendable su uso para modular tratamiento en el seguimiento de insuficiencia cardiaca crónica

Although there are data to suggest that serial natriuretic peptide guidance can reduce the rates of hospitalization and death from heart failure in patients under age 75, there is not enough evidence to recommend routine measurements for the outpatient management of heart failure.

A 2009 focused update to the joint American College of Cardiology and American Heart Association 2005 guidelines19 concluded that using natriuretic peptide levels to guide heart failure therapy is not well established (class 2b, level of evidence C).

Measurement of natriuretic peptides can be useful in evaluating and risk-stratifying patients presenting in the urgent care setting in whom the clinical diagnosis of heart failure is uncertain. These measurements are to be viewed as part of the total evaluation but are not to be used in isolation to confirm or exclude the presence of heart failure or to monitor the patient for decompensation.

Natriuretic peptide measurement is not a substitute for the information derived from a good history (dyspnea, orthopnea, paroxysmal nocturnal dyspnea) and physical examination (eg, weight, jugular venous distention, crackles, a third heart sound, edema).

The consensus opinion remains that the favorable outcomes with natriuretic peptide guidance in clinical trials were due to better adherence and continuous up-titration of medications to maximally tolerated target doses of angiotensin-converting enzyme inhibitors and beta-blockers, in addition to closer follow-up of patients in those groups.20 This can be done without serial natriuretic peptide measurements.

EMA Recommends New Contraindications and Warnings for Aliskiren-Containing Medicines | DocGuide

Source: DGNews
EMA Recommends New Contraindications and Warnings for Aliskiren-Containing Medicines

LONDON – February 17, 2012 -- The European Medicines Agency finalised a review
of aliskiren-containing medicines, recommending that these medicines should be
contraindicated in patients with diabetes or moderate to severe renal
impairment who take angiotensin converting enzyme (ACE) inhibitors or
angiotensin receptor blockers (ARBs). In addition, the Agency recommended the
inclusion of a warning that the combination of aliskiren and ACE inhibitor or
ARB is not recommended in all other patients because adverse outcomes cannot be
excluded.

Aliskiren-containing medicines are approved for the treatment of essential
hypertension.

Doctors should stop prescribing aliskiren-containing medicines to patients with
diabetes (type 1 or type 2) or with moderate to severe kidney impairment who
are also taking an ACE inhibitor or ARB, and should consider alternative
antihypertensive treatment as necessary.

For all other patients receiving aliskiren-containing medicines in combination
with an ACE inhibitor or an ARB, the balance of benefits and risks of
continuing treatment should be considered carefully.

Patients should discuss their treatment with their doctor at their next
scheduled (non-urgent) appointment. They should not stop any of their treatment
before speaking to their doctor, because stopping anti-hypertensive medication
without medical supervision can put them at risk.

Patients in clinical trials with aliskiren should contact their study site for
guidance on their medication.

The recommendations follow a review of all available safety data by the
Agency’s Committee for Medicinal Products for Human Use (CHMP). The review
was started in December 2011 after the Agency was informed by the marketing
authorisation holder of the decision to terminate the ALTITUDE study early.
This placebo-controlled phase III trial included patients with type 2 diabetes
and renal impairment and/or cardiovascular disease. In most patients, arterial
blood pressure was adequately controlled. The patients included in the trial
received aliskiren in addition to either an ACE inhibitor or an ARB.

Although the information available at the time was limited, the CHMP gave
interim recommendations in December 2011, advising doctors that they should not
prescribe aliskiren-containing medicines to diabetic patients in combination
with ACE inhibitors or ARBs.

Since then further data and analyses from the ALTITUDE study, alongside all
data from other studies and spontaneous reports of suspected adverse drug
reactions, have become available and were reviewed by the CHMP. The data
suggest a risk of adverse outcomes (hypotension, syncope, stroke, hyperkalaemia
and changes in renal function, including acute renal failure) when aliskiren is
combined with ACE inhibitors or ARBs, especially in diabetic patients and those
with impaired renal function. Although less evidence is available for other
patient groups, adverse outcomes cannot be excluded and therefore the
CHMP no longer recommends the use of this combination.

Healthcare professionals in the European Union will receive a letter shortly to
inform them of the changes to the prescribing information for
aliskiren-containing medicines.

SOURCE: European Medicine’s Agency

Combination treatment with atorvastatin plus niacin provides effective control of complex dyslipidemias

Source: Postgrad Med
Combination treatment with atorvastatin plus niacin provides effective control of complex dyslipidemias: a literature review; McKenney JM; Postgraduate Medicine 124 (1), 7-20 (Jan 2012)
Tags: acetylsalicylic acid atorvastatin Dyslipidemia nicotinic acid
Read/Add Comments | Email This | Print This | PubMed
Patients with dyslipidemia receive a cardiovascular benefit from lowering low-density lipoprotein cholesterol (LDL-C). Atorvastatin is currently one of the most effective approved medications for lowering LDL-C, and has been shown to significantly reduce cardiovascular risk in many patient groups. However, even with substantial lowering of LDL-C with atorvastatin, patients still have a residual risk for coronary heart disease. Elevated triglyceride levels and low high-density lipoprotein cholesterol (HDL-C) levels may contribute to this risk. Approved medications targeting these secondary lipid parameters include fibrates, omega-3 fatty acids, and niacin. Among these medications, niacin provides the optimal increase in HDL-C levels and has efficacy similar to the other medications in lowering triglyceride levels. However, there are challenges to adherence with niacin treatment. The most common challenge during niacin treatment is flushing, although it typically decreases with ongoing use and can be ameliorated by pretreatment with aspirin and counseling by the prescriber. A combination of atorvastatin and niacin may provide more complete normalization of the lipid profile and increased cardiovascular benefits. A literature review of the PubMed and Embase databases was conducted for clinical studies that reported on the lipid-modifying efficacy of the atorvastatin plus niacin combination. Identified studies involved patients at risk for coronary heart disease and patients with established coronary heart disease. Overall, the studies were small but indicated that atorvastatin in combination with niacin was efficacious in normalizing lipid parameters. Larger lipid studies as well as studies evaluating cardiovascular outcomes during atorvastatin plus niacin treatment are warranted.

Androgen Deprivation for Prostate Cancer Ups PAD Risk

Androgen Deprivation for Prostate Cancer Ups PAD Risk

NEW YORK (Reuters Health) Feb 15 - A population-based observational study indicates that androgen deprivation therapy for nonmetastatic prostate cancer is tied to an increased risk of venous thromboembolism (VTE) and peripheral artery disease (PAD).

"Additional research is needed to better understand the potential risks and benefits of androgen deprivation therapy (ADT), so that this treatment can be targeted to patients for whom the benefits are clearest," conclude the Boston-based authors of the report.

In their paper, published online February 1 in European Urology, Dr. Jim C. Hu at Brigham and Women's Hospital and colleagues point out that ADT is known to increase the risk of coronary artery disease and stroke, but there's little information about its effect on peripheral vascular risk.

The research team used data from the population-based SEER tumor registry linked to Medicare data to identify 182,757 men ages 65 and older with nonmetastatic prostate cancer.

"We focused on men with nonmetastatic disease, because the indication for ADT remains unclear for many men treated in this setting, and thus the risk of harm is potentially greater," the researchers explain.

Half the men received ADT, either with gonadotropin-releasing hormone agonists (47.8%) or orchiectomy (2.2%).

During a median follow-up of 5.1 years, PAD incidence rates per 1000 person years were 30.5 in the GnRH group, 27.1 in the orchiectomy group, and 21.0 without ADT. Corresponding rates of incident VTE were 13.2, 14.7 and 10.1 per 1000 person-years.

After adjustment, GnRH agonist use was associated with significantly increased risk of PAD (hazard ratio 1.16) and VTE (HR 1.10). Similarly, the hazard ratios associated with orchiectomy were 1.13 and 1.27, respectively.

The authors also found that increasing levels of comorbidity were strongly associated with these outcomes. In discussing the findings, they comment: "It is also notable that the increased risks (with ADT) were relatively modest and smaller than for the risk of increasing levels of comorbidity. This finding underscores the importance of addressing known risk factors for PAD and venous thromboembolism, especially for patients who are likely to benefit from ADT."

Reuters Health Information © 2012

ALISKIREN Se suspende el estudio ALTITUDE

Se suspende el estudio ALTITUDE con aliskiren Publicado por RIM (0:49) en la categoría Ensayos clínicos Se ha finalizado anticipadamente el estudio ALTITUDE debido al incremento de efectos adversos en el grupo tratado con aliskiren respecto al grupo placebo. El estudio ALTITUDE tenía previsto finalizar tras cuatro años de seguimiento en 2012. Su objetivo era evaluar en aproximadamente 8.600 diabéticos tipo 2 con alto riesgo de eventos cardiovasculares y renales, si añadir aliskiren 300 mg/dia al tratamiento convencional con IECA o con ARA 2 reduce la morbimortalidad cardiovascular y renal. La nota emitida por Novartis señala que en el brazo del estudio en el que se añadió aliskiren al tratamiento convencional, tras 18-24 meses, hubo un incremento en la incidencia de ictus no fatal, complicaciones renales, hiperpotasemia e hipotensión. El comité de seguimiento de datos (DMC) independiente que supervisa el ensayo concluyó que era poco probable que los pacientes se beneficiaran de este tratamiento que se añadió a la terapia estándar con IECA o ARA 2 con el fin producir un bloqueo dual en el sistema renina angiotensina aldosterona (SRAA). A pesar de que otros estudios como el VALIANT y ONTARGET ya han fracasado en mostrar beneficios con el bloqueo dual del SRAA con IECA y ARA 2, se esperaba hallarlos con un inhibidor directo de la renina.

Cefpodoxime doesn't match ciprofloxacin for acute cystitis

JAMA : The Journal of the American Medical Association Cefpodoxime doesn't match ciprofloxacin for acute cystitis February 8, 2012 ST LOUIS (MD Consult) - The cephalosporin antibiotic cefpodoxime is not as effective as the fluoroquinolone ciprofloxacin for treatment of acute cystitis, reports a trial in the February 8, 2012, issue of The Journal of the American Medical Association. The randomized, double-blind trial included 300 women, aged 18 to 55, with acute, uncomplicated cystitis. One group received ciprofloxacin, 250 mg twice daily, and the other received cefpodoxime proxetil, 100 mg twice daily. Both treatments were given for 3 days. Clinical cure rates, defined as not requiring antimicrobial treatment during follow-up, were compared at 30 days. Clinical and microbiologic cure rates at the first follow-up visit and vaginal Escherichia coli colonization rate at each visit were assessed as well. The study specified a 10% noninferiority margin between treatments. The lead author was Dr Thomas M. Hooton of University of Miami. On intention-to-treat analysis considering patients lost to follow-up as cured, clinical cure rates were 93% with ciprofloxacin and 82% with cefpodoxime. With patients lost to follow-up considered as nonresponders, the cure rates were 83% and 71%, respectively. Microbiologic cure rates were 96% with ciprofloxacin versus 81% with cefpodoxime. For all outcomes, the difference between treatments exceeded the 10% noninferiority margin. Colonization with E. coli was found at the first follow-up visit in 16% of the ciprofloxacin group versus 40% of the cefpodoxime group. Because of rising resistance rates, there is a need for non-fluoroquinolone alternatives for treatment of urinary tract infections. However, the new trial finds that cefpodoxime is not as an effective as ciprofloxacin for initial treatment of acute uncomplicated cystitis. The investigators conclude, "These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum β-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis." JAMA. 2012;307:583-589.

PPI Diarrea Clostridiun difficile

Source: DGNews | PPIs May Increase Risk of Clostridum difficile-Associated Diarrhoea, Says FDA Tags: Bacterial Infections dexlansoprazole Esophagitis/GERD H. Pylori/Ulcer lansoprazole naproxen omeprazole sodium bicarbonate Read/Add Comments(2) | Email This | Print This ROCKVILLE, Md --February 8, 2012 --The US Food and Drug Administration (FDA) has notified the public that the use of proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrheal (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhoea that does not improve. The FDA is working with manufacturers to include information about the increased risk of CDAD with use of PPIs in the drug labels. The FDA is also reviewing the risk of CDAD in users of histamine H2 receptor blockers. Information for Healthcare Professionals: • A diagnosis of CDAD should be considered for PPI users with diarrhoea that does not improve. • Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs. • Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program: • Complete and submit the report Online: www.fda.gov/MedWatch/report.htm • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 List of PPIs: • rabeprazole sodium (AcipHex) • dexlansoprazole (Dexilant) • esomeprazole magnesium (Nexium) • Over-the-counter omeprazole • Over-the-counter lansoprazole (Prevacid and Prevacid 24hr) • Omeprazole (Prilosec) • pantoprazole sodium (Protonix) • esomeprazole magnesium and naproxen (Vimovo) • omeprazole and Sodium bicarbonate (Zegerid SOURCE: US Food and Drug Administration

Aliskiren penetrates adipose and skeletal muscle tissue and reduces renin-angiotensin system activity in obese hypertensive patients

Aliskiren penetrates adipose and skeletal muscle tissue and reduces renin-angiotensin system activity in obese hypertensive patients; Boschmann M, Nussberger J, Engeli S, Danser AH, Yeh CM, Prescott MF, Dahlke M, Jordan J; Journal of Hypertension (Jan 2012) OBJECTIVE: In animals, the direct renin inhibitor aliskiren showed extensive tissue binding in the kidney and long-lasting renal effects. Aliskiren provides prolonged blood pressure-lowering effects following treatment discontinuation in patients. Therefore, we investigated whether aliskiren attains tissue concentrations sufficient to inhibit local renin-angiotensin system (RAS) activity in patients. METHODS: We included 10 hypertensive patients with abdominal adiposity in an open-label study. Following 1-2 weeks washout, patients received 2 weeks placebo, then 4 weeks aliskiren 300 mg once daily, followed by 4 weeks washout, and then 4 weeks amlodipine 5 mg once daily. Drug concentrations and RAS biomarkers were measured in interstitial fluid using microdialysis and in biopsies from abdominal subcutaneous adipose and skeletal muscle. RESULTS: We detected aliskiren in all compartments. After 4 weeks of treatment, microdialysate aliskiren concentrations (ng/ml) were 2.4 ± 2.1 (adipose) and 7.1 ± 4.2 (skeletal muscle), similar to plasma concentrations (8.4 ± 4.4); tissue concentrations (ng/g) were 29.0 ± 16.7 (adipose) and 107.3 ± 68.6 (skeletal muscle). Eight weeks after discontinuation, aliskiren was measurable in tissue biopsies but not in plasma or in interstitial fluid. Pooled microdialysate samples from two sets of four patients suggested reduction in tissue angiotensin II with aliskiren but not with amlodipine. CONCLUSION: In obese hypertensive patients, aliskiren penetrates adipose and skeletal muscle tissue at levels that are apparently sufficient to reduce tissue RAS activity. Furthermore, tissue binding may contribute to aliskiren's prolonged blood pressure-lowering effect following discontinuation.

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property

Source: Dig Liver Dis Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property; Hyogo H, Yamagishi SI, Maeda S, Kimura Y, Ishitobi T, Chayama K; Digestive and Liver Disease (Jan 2012) BACKGROUND: We have previously found that atorvastatin decreases liver injury markers in patients with nonalcoholic steatohepatitis. However, how atorvastatin treatment ameliorates the disease activity in nonalcoholic steatohepatitis patients remains unknown. AIMS: We examined here which anthropometric, metabolic and inflammatory variables were improved and related with amelioration of disease activity in atorvastatin-treated nonalcoholic steatohepatitis patients. METHODS: Forty-two biopsy-proven nonalcoholic steatohepatitis patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10mg/day) for 12 months. RESULTS: Atorvastatin significantly decreased liver transaminase, γ-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-α levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that γ-glutamyl transpeptidase, tumour necrosis factor-α and liver to spleen density ratio (inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio. CONCLUSION: The present study suggests that atorvastatin improves the disease activity of nonalcoholic steatohepatitis partly via its tumour necrosis factor-α-lowering property.

Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease

Source: J Allergy Clin Immunol Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease; Ingelsson E, Yin L, Bäck M; Journal of Allergy and Clinical Immunology (JACI) (Jan 2012) BACKGROUND: The leukotriene pathway has been associated with an increased cardiovascular risk. However, the effects of the antileukotriene treatment used in asthmatic patients on cardiovascular outcomes have remained largely unexplored. OBJECTIVE: We sought to examine a potential protective role of the leukotriene receptor antagonist montelukast on future risk of incident and recurrent myocardial infarction and ischemic stroke. METHODS: A nationwide population-based cohort of approximately 7 million persons integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational, and Emigration Registers was followed from July 1, 2005, to December 31, 2008. Analyses were performed in the whole population after exclusion of subjects with a prior cardiovascular diagnosis (incident events; sample size, n = 6,910,923 for myocardial infarction and n = 6,932,578 for stroke) and in subjects with a prior diagnosis (recurrent events; n = 153,937 and n = 132,291 for stroke and myocardial infarction, respectively). RESULTS: Cox proportional hazard ratios (HRs) did not reveal an association of montelukast use with incident events. In contrast to these findings, montelukast use was associated with a lower risk for recurrent stroke (HR, 0.62; 95% CI, 0.38-0.99) accounting for age, sex, education level, and yearly income. Adjusting the latter finding also for respiratory and cardiovascular medications and diagnoses revealed similar point estimates (HR, 0.62; 95% CI, 0.39-1.0). Post hoc analyses revealed a significant association of montelukast use with a lower risk for recurrent myocardial infarction in male subjects (HR, 0.65; 95% CI, 0.43-0.99). CONCLUSION: These data provide a first indication for a potential role of the antiasthma drug montelukast for secondary prevention of cardiovascular