Comparison of Effects of Atorvastatin (20 mg) Versus Rosuvastatin (10 mg) Therapy on Mild Coronary Atherosclerotic Plaques (from the ARTMAP Trial)

Source: Am J Cardiology Comparison of Effects of Atorvastatin (20 mg) Versus Rosuvastatin (10 mg) Therapy on Mild Coronary Atherosclerotic Plaques (from the ARTMAP Trial); Lee CW, Kang SJ, Ahn JM, Song HG, Lee JY, Kim WJ, Park DW, Lee SW, Kim YH, Park SW, Park SJ; American Journal of Cardiology (Mar 2012) Tags: atorvastatin rosuvastatin Vascular Disorders Read/Add Comments | Email This | Print This | PubMed High-dose rosuvastatin induces regression of coronary atherosclerosis, but it remains uncertain whether usual-dose statin has similar effects. We compared the effects of atorvastatin 20 mg/day versus rosuvastatin 10 mg/day on mild coronary atherosclerotic plaques (20% to 50% luminal narrowing and lesion length>10 mm) using intravascular ultrasound (IVUS). Three hundred fifty statin-naive patients with mild coronary atherosclerotic plaques were randomized to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. IVUS examinations were performed at baseline and 6-month follow-up. Primary end point was percent change in total atheroma volume (TAV) defined as (TAV at 6 months - TAV at baseline)/(TAV at baseline) × 100. Evaluable IVUS was obtained for 271 patients (atorvastatin in 143, rosuvastatin in 128). Clinical characteristics, lipid levels, and IVUS measurements at baseline were similar between the 2 groups. At 6-month follow-up, percent change in TAV was significantly less in the atorvastatin group than in the rosuvastatin group (-3.9 ± 11.9% vs -7.4 ± 10.6%, respectively, p = 0.018). In contrast, change in percent atheroma volume was not different between the 2 groups (-0.3 ± 4.2 vs -1.1 ± 3.5, respectively, p = 0.157). Compared to baseline, TAV and TAV at the most diseased 10-mm subsegment were significantly decreased in the 2 groups (p<0.001). Changes in lipid profiles at 6-month follow-up were similar between the 2 groups. In conclusion, usual doses of atorvastatin and rosuvastatin induced significant regression of coronary atherosclerosis in statin-naive patients, with a greater decrease in favor of rosuvastatin.

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Prehypertension: To Treat or Not To Treat Should No Longer Be the Question

Prehypertension: To Treat or Not To Treat Should No Longer Be the Question

Shawn G. Kwatra, Amanda E. Kiely, Madan M. Kwatra

Wake Forest University School of Medicine
Winston-Salem, NC (Kwatra)
Department of Ophthalmology
The Johns Hopkins University School of Medicine
Baltimore, MD (Kiely)
Department of Anesthesiology
Duke University Medical Center
Durham, NC (Kwatra)

To the Editor:

We read with great interest the article by Selassie et al1
that progression from prehypertension to full-blown hypertension occurs more rapidly in blacks, with 50% transitioning to hypertension within 1.7 years compared with 2.7 years in whites. Although the authors highlight the importance of controlling prehypertension, we feel that the authors missed an opportunity to stress the feasibility of using antihypertensive drugs to control prehypertension. As we argued previously,2
the recommendation by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to treat prehypertension only with lifestyle changes3
is unlikely to work. Our view that prehypertension should be treated pharmacologically is supported by a recent meta-analysis of 16 trials involving 70664 patients.4
This analysis found that prehypertensive patients randomized to the active treatment arm had a 22% reduction in the risk of stroke as compared with the placebo group. In addition, treatment of prehypertension with an angiotensin receptor blocker reduced the risk of incident hypertension.5
Thus, the debate of whether to treat prehypertension should end. Treating prehypertension is medically sound and economically viable,2
and benefits of treatment are now apparent.

Thiazolidinediones can prevent new onset atrial fibrillation in patients with non-insulin dependent diabetes

International Journal of Cardiology
Volume 156, Issue 2 , Pages 199-202, 19 April 2012
Thiazolidinediones can prevent new onset atrial fibrillation in patients with non-insulin dependent diabetes
Tze-Fan Chao, Hsin-Bang Leu, Chin-Chou Huang, Jaw-Wen Chen, Wan-Leong Chan, Shing-Jong Lin, Shih-Ann Chen
Abstract
Background
Accumulative evidence suggested that oxidative stress and inflammation were involved in the pathogenesis of atrial fibrillation (AF). Thiazolidinediones (TZDs), agonists of peroxisome proliferator-activated receptor gamma (PPAR-γ), have been proven to have anti-inflammatory and anti-oxidant effects in addition to their anti-diabetic activity. The goal of this nationwide, population based cohort study was to evaluate whether the use of TZDs will protect diabetic patients from AF.

Methods
The study population was comprised of 12,065 non-insulin dependent diabetic patients identified from the “National Health Insurance Research Database” released by the Taiwan National Health Research Institutes. Among the study patients, a total of 4137 patients with TZD use were recognized as the study cohort and 7928 patients without TZD use were included as the comparison cohort. The study endpoint was defined as AF occurrence during the follow up period.

Results
During the follow up of 63±25months, 194 patients (1.6% of the study population) developed AF: 49 from the study cohort (1.2% of the TZD group) and 145 from the comparison cohort (1.8% of the non-TZD group). After an adjustment for the baseline characteristics and medications, the TZDs independently protected diabetic patients from new-onset AF with a hazard ratio of 0.69 (95% confidence interval=0.49–0.91, p value=0.028).

Conclusion
In this cohort study, we demonstrated that TZDs had obvious protective effects on the development of AF in diabetic patients. Drugs acting as ligands to the PPAR-γ may be potential up-stream therapies for AF prevention.

Moderate Drinking After Heart Attack Tied to Lower Mortality

March 27, 2012 — Men who drink 2 glasses of alcohol a day after surviving a heart attack are less likely to die from heart disease or other causes than either nondrinkers or those who drink more, according to a study of nearly 2000 health professionals published online March 28 in the European Heart Journal.

Jennifer K. Pai, ScD, assistant professor of medicine and associate epidemiologist, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues used data from the Health Professionals Follow-up Study to track the survival of 1818 men who suffered a heart attack between 1986 and 2006, following-up some participants for as long as 20 years. During the follow-up, some 468 men died.

Although moderate alcohol consumption (between 10.0 and 29.9 g/day) is associated with a lower risk for heart disease and reduced mortality from all causes in healthy populations, the data on post–myocardial infarction (MI) drinking is limited and somewhat contradictory, the authors write.

In the current study, moderate drinking showed clear benefits post-MI in both multivariable-adjusted and unadjusted hazard ratios (HRs). The multivariable-adjusted HR for death from any cause for moderate drinkers compared with nondrinkers was 0.66 (95% confidence interval [CI], 0.51 - 0.86). For light drinkers, who reported consuming between 0.1 and 9.9 g of alcohol per day, the HR was 0.78 (95% CI, 0.62 - 0.97). For heavy drinkers, who consumed 30 g or more of alcohol daily, the HR for all-cause mortality was 0.87 (95% CI, 0.61 - 1.25; P quadratic = .006). The data were adjusted for age at diagnosis, questionnaire follow-up cycle, smoking, body mass index (BMI), physical activity, diabetes, hypertension, lipid-lowering medications, aspirin use, and heart failure.

When just cardiovascular mortality is considered, the benefit for moderate drinkers is more pronounced, with a multivariable-adjusted HR of 0.58 (95% CI, 0.39 - 0.84) compared with 0.74 for light drinkers (95% CI, 0.54 - 1.02) and 0.98 for heavy drinkers (95% CI, 0.60 - 1.60; P quadratic = .003).

"Our findings clearly demonstrate that long-term moderate alcohol consumption among men who survived a heart attack was associated with reduced risk of total and cardiovascular mortality," Dr. Pai said in a news release. "We also found that among men who consumed moderate amounts of alcohol prior to a heart attack, those who continued to consume alcohol 'in moderation' afterwards also had better long-term prognosis."

In this study, participants responded to a questionnaire about alcohol consumption and diet every 4 years and were asked about lifestyle and medical factors (including smoking and BMI) every 2 years. Previous prospective studies examining post-MI alcohol consumption did not include validated measures of pre- and post-MI drinking with long-term follow-up.

Most participants in this study did not change alcohol consumption levels after MI diagnosis. Multivariable-adjusted HRs for total mortality, considering pre-MI alcohol only, compared with nondrinkers, were 0.91 (95% CI, 0.72 - 1.16) for light drinkers, 0.70 (95% CI, 0.52 - 0.93) for moderate drinkers, and 1.00 (95% CI, 0.70 - 1.42) for heavy drinkers. When considering only post-MI consumption, multivariable HRs for total mortality were 0.90 (95% CI, 0.71 - 1.13) for light drinkers, 0.70 (95% CI, 0.52 - 0.92) for moderate drinkers, and 0.79 (95% CI, 0.53 - 1.17) for heavy drinkers.

For cardiovascular morality, the multivariable-adjusted HR for pre-MI alcohol consumption was 0.74 (95% CI, 0.52 - 1.04) for light drinkers, 0.78 (95% CI, 0.53 - 1.15) for moderate drinkers, and 0.85 (95% CI, 0.50 - 1.44) for heavy drinkers. When considering post-MI consumption only, the multivariable HRs for cardiovascular mortality were 0.73 (95% CI, 0.53 - 1.01) for light drinkers, 0.62 (95% CI, 0.42 - 0.93) for moderate drinkers, and 0.77 (95% CI, 0.44 - 1.35) for heavy drinkers.

The study results hinted at an inverse association between alcohol consumption and mortality among patients who increased alcohol consumption, from less than 10 g/day before a heart attack to 10 to 29.9 g/day post-MI. The small number of cases in the analysis led to a CI that crossed 1.0 in multivariable adjustment, and so was not statistically significant.

The data showed that heavy drinking carried a hazard ratio essentially as high as nondrinking.

"Our results, showing the greatest benefit among moderate drinkers and a suggestion of excess mortality among men who consumed more than two drinks a day after a heart attack, emphasise the importance of alcohol in moderation," Dr. Pai said in the release.

"In addition, other studies have shown that any benefits from light drinking are entirely eliminated after episodes of binge drinking," she noted.

The data does not necessarily extrapolate to women, Dr. Pai said in the release. "However, in all other cases of alcohol and chronic disease, associations are similar except at lower quantities for women. Thus, an association is likely to be observed at 5-14.9g per day, or up to a drink a day for women."

The authors have disclosed no relevant financial relationships.

Eur Heart J. Published online March 28, 2012. Abstract

Medscape Medical News © 2012 WebMD, LLC
Send comments and news tips to news@medscape.net.

Dabigatran y enfermedad renal

Dabigatran (OCTOBER 2011)
Authors
PATRICIO A. PAZMIÑO, PhD, MD, FACP, FASN
Nephrology, Internal Medicine & Hypertension (NIH) Center, El Paso, TX
TO THE EDITOR: I read with interest the review of dabigatran (Pradaxa) by Drs. Wartak and Bartholomew, which provides an excellent overview of this new oral anticoagulant.1
This article does not mention clearly two key points about the guidelines for using dabigatran, which are different in the United States than in the other 75 countries where it has been approved.1 First, the RE-LY trial2,3 excluded patients with a creatinine clearance rate less than 30 mL/min/1.73 m2, a common situation in the elderly. Second, in contrast to other countries, the US Food and Drug Administration (FDA) approved dabigatran for patients with a creatinine clearance rate of 15 to 30 mL/min/1.73 m2, although at a lower dose.3 No dose adjustment is suggested in patients with less severe (mild or moderate) renal impairment.3 This may lead to potential misuse and problems. In fact, lethal side effects have been reported in France by Legrand et al.4 Furthermore, a report is in press on dabigatran-associated acute renal failure,5 and recently the German publication Die Zeit reported 50 deaths from bleeding in patients with atrial fibrillation treated with dabigatran.6
Therefore, despite suggestions that dabigatran does not require monitoring of its effects during treatment,1,3 renal, hematologic, and hepatic variables should be monitored before and after initiation of dabigatran5 until more experience is gained with this new drug, and especially in the elderly and those with chronic kidney disease that is stage 4 (estimated glomerular filtration rate 15–29 mL/min/1.73 m2) or stage 5 (< 15 mL/min/1.73 m2).
Copyright© 2012 The Cleveland Clinic Foundation
REFERENCES

↵ Wartak SA, Bartholomew JR . Dabigatran: will it change clinical practice? Cleve Clin J Med 2011; 78:657–664. Abstract/FREE Full Text
↵ Connolly SJ, Ezekowitz MD, Yusuf S, et al., RE-LY Steering Committee and Investigators . Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139–1151. CrossRefMedline
↵ Pradaxa (prescribing information) . Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals, Inc, 2011.
↵ Legrand M, Mateo J, Aribaud A, et al. The use of dabigatran in elderly patients. Arch Intern Med 2011; 171:1285–1286. Abstract/FREE Full Text
↵ Pazmiño PA . Dabigatran-associated acute renal failure (DAARF). El Paso Physician 2011. In press.
↵ Kaiser C . Pradaxa bleeding deaths raise concern. MedPageToday. www.medpagetoday.com/Cardiology/Strokes/29411. Accessed February 9, 2012.

Prolonged QTc Interval and Torsades de Pointes Induced by Citalopram

Prolonged QTc Interval and Torsades de Pointes Induced by Citalopram; Deshmukh A, Ulveling K, Alla V, Abuissa H, Airey K; Texas Heart Institute Journal 39 (1), 68-70 (2012)

Citalopram is a selective serotonin reuptake inhibitor with a favorable cardiac-safety profile. Corrected QT interval (QTc) prolongation and cardiac arrhythmias have not been previously reported in association with citalopram use except in the presence of overdose, abnormal electrolyte values, or renal or liver failure. Herein, we report the case of a 40-year-old woman with mental depression who presented with a prolonged QTc interval and torsades de pointes after the initiation of citalopram at therapeutic doses. The QTc interval improved when citalopram therapy was discontinued. We recommend that clinicians investigate the family history for sudden deaths and perform baseline electrocardiography before prescribing citalopram. We also recommend routine electrocardiographic testing during citalopram therapy, and that patients with long QT syndrome avoid taking citalopram.

Coronary artery bypass grafting generally remains superior to drug-eluting stents in left main coronary artery disease

CABG still trumps stents in left main coronary artery disease Coronary artery bypass grafting generally remains superior to drug-eluting stents in left main coronary artery disease, especially in patients with complex anatomy and multivessel disease, despite advances in stent technology, a meta-analysis by Sydney researchers has concluded. Dr Christopher Cao, from St George Hospital, and colleagues identified three randomised controlled trials and 11 observational studies which included a total of 5,628 patients. There was a higher incidence of major cardiovascular and cerebrovascular events (MACCE) at 12 months and beyond in patients receiving stents. They were also more likely to need repeat revascularisation, but less likely to have a stroke. All-cause mortality was similar in CABG and stent patients at 30 days and during follow-up beyond one year, but lower in stent patients at 12 months. Stent patients were more likely than CABG patients to have a myocardial infarction at 30 days, but the rates were similar at one year and beyond. Surgery had traditionally been regarded as superior to stenting in patients with left main disease but the situation had not been thoroughly reviewed since the use of drug-eluting stents had become widespread, the authors said. The current results suggested that drug-eluting stents “…may have an important clinical role for selected patients with percutaneously-amenable left main disease who are poor candidates for surgery,” they said. They cautioned that the results included in the meta-analysis were collected from highly selected groups of patients treated in tertiary referral centres and their outcomes might not reflect those obtained in routine care. Most patients with left main disease had multivessel coronary artery disease but they might have been under-represented in the clinical trials and more likely to have CABG in the observational studies. Longer-term follow-up of larger numbers of patients were still needed, they said. Journal of Thoracic and Cardiovascular Surgery; doi:10.1016/j.jtcvs.2012.02.004, despite advances in stent technology, a meta-analysis by Sydney researchers has concluded. Dr Christopher Cao, from St George Hospital, and colleagues identified three randomised controlled trials and 11 observational studies which included a total of 5,628 patients. There was a higher incidence of major cardiovascular and cerebrovascular events (MACCE) at 12 months and beyond in patients receiving stents. They were also more likely to need repeat revascularisation, but less likely to have a stroke. All-cause mortality was similar in CABG and stent patients at 30 days and during follow-up beyond one year, but lower in stent patients at 12 months. Stent patients were more likely than CABG patients to have a myocardial infarction at 30 days, but the rates were similar at one year and beyond. Surgery had traditionally been regarded as superior to stenting in patients with left main disease but the situation had not been thoroughly reviewed since the use of drug-eluting stents had become widespread, the authors said. The current results suggested that drug-eluting stents “…may have an important clinical role for selected patients with percutaneously-amenable left main disease who are poor candidates for surgery,” they said. They cautioned that the results included in the meta-analysis were collected from highly selected groups of patients treated in tertiary referral centres and their outcomes might not reflect those obtained in routine care. Most patients with left main disease had multivessel coronary artery disease but they might have been under-represented in the clinical trials and more likely to have CABG in the observational studies. Longer-term follow-up of larger numbers of patients were still needed, they said. Journal of Thoracic and Cardiovascular Surgery; doi:10.1016/j.jtcvs.2012.02.004

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New Dabigratan meta-analisis Efectos colaterales

New dabigatran meta-analysis questions 'euphoria' 20 March, 2012 Paddy Wood 0 comments A new meta-analysis shedding “alarming” light on the cardiovascular side-effects of dabigatran is a sobering wake-up call to a medical community too quick to embrace new treatments, experts argue. In an analysis of seven core trials involving more than 30,000 patients, American researchers found the anticoagulant was associated with an average 33% increased risk of MI or ACS relative to control drugs including warfarin, enaxoparin, and placebo. The new study was prompted by the discovery, after publication, of an additional 32 cases of MI in participants in RE-LY–the original and largest study of dabigratran –which found a 38% increased risk of MI compared to warfarin. The drug has sparked contention since it was first approved by the TGA in 2008. After an extension in April 2011 to include indications for stroke in atrial fibrillation patients, the TGA issued a safety advisory in November after increasing reports of bleeding-related events. The new analysis, published in the Archives of Internal Medicine, again casts the spotlight on the drug’s side effects and highlights the risks of over eagerness to embrace new treatments, experts have said. Physicians should “step back for a moment, take their own pulse, and retain a critical view as a powerful new drug enters clinical use a potentially massive scale”, argue Israeli doctors Jeremy Jacobs and Jochanan Stressman in an accompanying editorial. Because new drugs may have dangers that become known “long after the relatively pristine data of clinical trials have given way to the gritty reality of daily clinical drug use,” continued critical appraisal was crucial. They said the enthusiasm to embrace new treatments –“nearly to the level of euphoria” –must be restrained in the interests of patient care. The editor of the journal, Rita Redberg, said the results emphasised the need to reappraise the risk and benefits of dabigatran. However, the authors of the study said the benefits probably still outweighed risks in patients with AF given the profound reduction in ischemic stroke and sundry clot risk, shown in RE-LY to be 34% relative to warfarin. Cardiac risk should be further investigated, they said. Arch Int Med;doi:10.1001/archinternmed.2011.1666

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Combination Therapy Including Glucocorticoids: The New Gold Standard for Early Treatment in Rheumatoid Arthritis?

From the Department of Rheumatology and Clinical Immunology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, and Diakonessenhuis, Utrecht; St. Antonius Hospital, Nieuwegein; Meander Medical Center, Amersfoort; Tergooi Hospital, Hilversum; St. Jansdal Hospital, Harderwijk; and Flevohospital, Almere, the Netherlands.

Abstract

Background: Treatment strategies for tight control of early rheumatoid arthritis (RA) are highly effective but can be improved.

Objective: To investigate whether adding prednisone, 10 mg/d, at the start of a methotrexate (MTX)–based treatment strategy for tight control in early RA increases its effectiveness.

Design: A 2-year, prospective, randomized, placebo-controlled, double-blind, multicenter trial (CAMERA-II [Computer Assisted Management in Early Rheumatoid Arthritis trial-II]). (International Standard Randomised Controlled Trial Number: ISRCTN 70365169)

Setting: 7 hospitals in the Netherlands.

Patients: 236 patients with early RA (duration <1 year).

Intervention: Patients were randomly assigned to an MTX-based, tight control strategy starting with either MTX and prednisone or MTX and placebo. Methotrexate treatment was tailored to the individual patient at monthly visits on the basis of predefined response criteria aiming for remission.

Measurements: The primary outcome was radiographic erosive joint damage after 2 years. Secondary outcomes included response criteria, remission, and the need to add cyclosporine or a biologic agent to the treatment.

Results: Erosive joint damage after 2 years was limited and less in the group receiving MTX and prednisone (

n = 117) than in the group receiving MTX and placebo (n = 119). The MTX and prednisone strategy was also more effective in reducing disease activity and physical disability, achieving sustained remission, and avoiding the addition of cyclosporine or biologic treatment. Adverse events were similar in both groups, but some occurred less in the MTX and prednisone group.

Limitation: A tight control strategy for RA implies monthly visits to an outpatient clinic, which is not always feasible.

Conclusion: Inclusion of low-dose prednisone in an MTX-based treatment strategy for tight control in early RA improves patient outcomes.

Effect of Chronic CPT-1 Inhibition on Myocardial Ischemia-Reperfusion Injury (I/R) in a Model of Diet-Induced

Effect of Chronic CPT-1 Inhibition on Myocardial Ischemia-Reperfusion Injury (I/R) in a Model of Diet-Induced Obesity
Mar 12, 2012 5:56 PM
Abstract
Purpose
By increasing circulating free fatty acids and the rate of fatty acid oxidation, obesity decreases glucose oxidation and myocardial tolerance to ischemia. Partial inhibition of fatty acid oxidation may improve myocardial tolerance to ischemia/reperfusion (I/R) in obesity. We assessed the effects of oxfenicine treatment on post ischemic cardiac function and myocardial infarct size in obese rats.
Methods
Male Wistar rats were fed a control diet or a high calorie diet which resulted in diet induced obesity (DIO) for 16 weeks. Oxfenicine (200 mg/kg/day) was administered to control and DIO rats for the last 8 weeks. Isolated hearts were perfused and infarct size and post ischemic cardiac function was assessed after regional or global ischemia and reperfusion. Cardiac mitochondrial function was assessed and myocardial expression and activity of CPT-1 (carnitine palmitoyl transferase-1) and IRS-1 (insulin receptor substrate-1) was assessed using Western blot analysis.
Results
In the DIO rats, chronic oxfenicine treatment improved post ischemic cardiac function and reduced myocardial infarct size after I/R but had no effect on the cardiac mitochondrial respiration. Chronic oxfenicine treatment worsened post ischemic cardiac function, myocardial infarct size and basal mitochondrial respiration in control rat hearts. Basal respiratory control index (RCI) values, state 2 and state 4 respiration rates and ADP phosphorylation rates were compromised by oxfenicine treatment.
Conclusion
Chronic oxfenicine treatment improved myocardial tolerance to I/R in the obese rat hearts but decreased myocardial tolerance to I/R in control rat hearts. This decreased tolerance to ischemia of oxfenicine treated controls was associated with adverse changes in basal and reoxygenation mitochondrial function. These changes were absent in oxfenicine treated hearts from obese rats.
Content Type Journal Article
Pages 1-12
DOI 10.1007/s10557-012-6377-1
Authors
Gerald Maarman, Departments of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa
Erna Marais, Departments of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa
Amanda Lochner, Departments of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa
Eugene F du Toit, Heart Foundation Research Center, School of Medical Science, Gold Coast Campus, Griffith University, Queensland, Australia
Journal Cardiovascular Drugs and Therapy
Online ISSN 1573-7241
Print ISSN 0920-3206

Late peripheral stent thrombosis due to stent fracture, vigorous exercise and hyporesponsiveness to clopidogrel

Late peripheral stent thrombosis due to stent fracture, vigorous exercise and hyporesponsiveness to clopidogrel.

AuthorsLinnemann B, et al. Show all Journal
Vasa. 2012 Mar;41(2):136-44.
Affiliation
Division of Vascular Medicine, Department of Internal Medicine, J.W. Goethe University Hospital, Frankfurt/Main, Germany.
Abstract
Late peripheral arterial stent thrombosis usually occurs due to haemodynamically relevant in-stent restenosis. However, late stent thrombosis may be multicausal. We report here the well-documented case of a 69-year-old man with acute thrombosis of the stented superficial femoral artery after a long-distance bicycle tour. Catheter-directed thrombolysis revealed a residual stenosis located at a stent fracture site. In addition, platelet function tests revealed an inadequate platelet response to clopidogrel. In conclusion, stent fracture, strenuous exercise and hyporesponsiveness to clopidogrel may have contributed to the development of late peripheral stent thrombosis.

Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents

Source: Europace
Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents; Bassand JP; Europace 14 (3), 312-24 (Mar 2012)
Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.

Renin Inhibitors and Cardiovascular and Renal Protection: An Endless Quest?

Renin Inhibitors and Cardiovascular and Renal Protection: An Endless Quest?; Azizi M, Ménard J; Cardiovascular Drugs and Therapy (Mar 2012)

Renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has become a major therapeutic approach in medicine since the end of the 1970's. Although these molecules were the first RAS blockers to be developed, it would have been physiologically and pharmacologically more pertinent to selectively inhibit renin itself. Indeed, the reaction between renin and its unique substrate, angiotensinogen, is the highly regulated and rate-limiting step of the RAS. The development of direct renin inhibitors (DRI) has been a slow and complex process and the synthesis of the first orally active DRI, aliskiren, was only achieved in the 2000's. Its pharmacological profile in patients with hypertension, diabetic nephropathy or heart failure, in addition to experimental evidence, suggests that aliskiren may be of value for the management of cardiovascular and renal diseases. However, the long-term, randomized, placebo-controlled, morbidity/mortality trial, ALTITUDE, which included 8,600 patients with type 2 diabetes, proteinuria and a high cardiovascular risk already treated with ACE inhibitors or ARBs was terminated in December 2011 because of futility and an increased incidence of serious adverse events in the aliskiren 300 mg arm. Other long-term studies are still ongoing to demonstrate the safety and efficacy of aliskiren to reduce cardiovascular morbidity and mortality in patients with heart failure and in elderly individuals (≥65 years) with systolic blood pressure of 130 to 159 mmHg, no overt cardiovascular disease, and a high cardiovascular risk profile. In the meantime, according to the European Medicines Agency recommendations, aliskiren should not be prescribed to diabetic patients in combination with ACE inhibitors or ARBs.

La FDA añade advertencias a la información para prescribir estatinas

La FDA añade advertencias a la información para prescribir estatinas

(Artículo original en inglés, heartwire; 28 feb. 2012) Silver Spring, EE UU — El tomar una estatina puede incrementar la glucemia y las concentraciones de glucohemoglobina (HbA1c), según los nuevos cambios en la información para prescribir aprobados por la Food and Drug Administration (FDA) hoy día para toda la clase de estos fármacos [1].

Según lo informó heartwire, estudios recientes [2] sobre las conocidas estatinas mostraron un incremento importante del riesgo de diabetes mellitus asociado al tratamiento con altas dosis de estatinas. El estudio Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) mostró un incremento del 27% en los casos de diabetes mellitus en pacientes que tomaban rosuvastatina en comparación con placebo. Así mismo, el subestudio Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) mostró que la atorvastatina en dosis altas puede empeorar el control de la glucemia.

Los nuevos cambios en la información para prescribir aprobados por la FDA también comprenden la posibilidad de que se presenten efectos secundarios cognitivos por lo general leves y reversibles. Además, la información para prescribir lovastatina se ha actualizado en grado importante para incluir contraindicaciones y limitaciones de la dosis del fármaco en pacientes que toman otros medicamentos que pueden aumentar el riesgo de lesión muscular.

La FDA señala que también es importante eliminar la recomendación de que en los pacientes con estatinas se lleve a cabo la vigilancia periódica sistemática de las enzimas hepáticas, pues este enfoque es ineficaz para detectar y evitar las lesiones hepáticas graves "infrecuentes e imprevisibles" relacionadas con las estatinas. El tratamiento con estatinas debe interrumpirse si el paciente muestra signos de lesión hepática importante, hiperbilirrubinemia o ictericia. La información para prescribir ahora señalará que el tratamiento con estatinas no se debiera reiniciar si no se pueden descartar estos fármacos como una causa de los problemas.

Aliskiren, amlodipine and hydrochlorothiazide triple combination for hypertension

Expert Rev Cardiovasc Ther. 2012 Mar;10(3):293-303. Aliskiren, amlodipine and hydrochlorothiazide triple combination for hypertension. Judd E, Jaimes EA. Source University of Alabama at Birmingham, Vascular Biology and Hypertension Program, 115 Community Health Services Building, 933 19th Street South, Birmingham, AL, USA. Abstract Cardiovascular-related morbidity and mortality is linked to hypertension with proportional gains in cardiovascular risk factor reduction with the lowering of blood pressure. Clinical trial data has shown that attaining goal blood pressure requires, for most patients, at least two antihypertensive medications, with a significant proportion requiring regimens of three or more medications. Single-pill triple combinations have returned to the market following results of increased efficacy and adherence over dual- and mono-therapy. The combination of aliskiren, amlodipine and hydrochlorothiazide is a rational choice for combination therapy and recent studies suggest that it is safe and effective in lowering blood pressure in patients who fail dual combination therapy.

The Role of Statin Therapy in the Prevention of Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

The Role of Statin Therapy in the Prevention of Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

AuthorsFang WT, et al. Show all Journal
Br J Clin Pharmacol. 2012 Feb 29. doi: 10.1111/j.1365-2125.2012.04258.x. [Epub ahead of print]

Affiliation
Department of Pharmacy, The first affiliated hospital with nanjing medical university, Nanjing, Jiangsu, PR China; 210029; Department of Pharmacy, Qianfoshan Hospital of Shandong Province, Jinan, Shandong, PR China, 250014;

Abstract
Aims:  To examine whether statins can reduce the risk of atrial fibrillation (AF). Background:  The use of statins had been suggested to protect against AF in some clinical observational and experimental studies but has remained inadequately explored. Methods:  Meta analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed. Results:  20 studies with 23577 patients were included in the analysis. 7 studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and 2 studies investigated mix population patients. Incidence or recurrence of AF occurred in 1543 patients. Overall, statins therapy was significantly associated with a decreased risk of AF compared with control (OR 0.49, 95% CI 0.37 to 0.65, p <0.00001). Beneficial effect was found in atorvastatin subgroup and simvastatin subgroup, but not found in pravastatin subgroup and rosuvastatin subgroup. Benefit of statin therapy seemed more markedly in secondary prevention (OR 0.34, 95% CI 0.18 to 0.64, p<0.0008) than primary prevention (OR 0.54, 95% CI 0.40 to 0.74, p< 0.0001). Conclusions:  Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient population and surgery types. Benefit of statin therapy seemed more markedly in secondary prevention than primary prevention. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Enemigo oculto La gran villana Descubrala

http://health.yahoo.net/experts/eatthis/9-sneaky-sources-sugar

Family tree helps estimate mortality risk for inherited arrhythmia patients

Family tree helps estimate mortality risk for inherited arrhythmia patients 29 February 2012 MedWire News: Dutch researchers have reconstructed family trees to estimate the mortality risk for individuals with inherited arrhythmia syndromes. “Our data might help to further guide treatment and screening strategies in an increasing group of (asymptomatic) mutation carriers who are detected by molecular genetic testing in families with an inherited arrhythmia syndrome,” report Eline Nannenberg (Academic Medical Center, Amsterdam) and co-authors. Although the risk for sudden cardiac death in symptomatic identified mutation carriers who are untreated is substantial, in asymptomatic carriers the risk is ill-defined, they explain. Preventive lifestyle advice and pharmacologic or invasive treatment can be offered, but these have side effects and impact quality of life. Nannenberg and team further investigated treatment options and screening strategies in asymptomatic patients using the Family Tree Mortality Ratio (FTMR) Method to ascertain mortality risk in six major autosomal syndromes caused by specific mutations. These were: long QT syndromes types 1, 2, and 3 (LQTS1, 2, 3); Brugada syndrome; SCN5A overlap syndrome (LQTS3/Brugada syndrome/conduction disease); and RYR2-gene related Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The researchers used Dutch archives to reconstruct family trees for patients with these syndromes and compared death statistics in 266 people who carried a mutation in a gene linked with arrhythmia, 904 family members with a 50% likelihood for having the mutation, and the general Dutch population. They were then able to identify age ranges during which the risk for mortality increased for mutation carriers and their family members, but they had not yet been diagnosed or treated for the condition. The findings are published in Circulation: Cardiovascular Genetics. They reveal that mortality risk in LQTS1 was significantly increased during childhood, at the ages of 1–19 years, at a standardized mortality ratio (SMR) of 3.0. Additional analysis identified a smaller specific age category in which the excess mortality was significant: between 1 and 9 years, at an SMR of 2.9. In LQTS1, the SMR increased starting from the age of 15 years, at an SMR of 2.6 from 15 to 19 years, but only reached significance between 30 and 39 years, at an SMR of 4.0. There was also severe excess mortality between the ages of 15 and 19 years, at an SMR of 5.8, in LQTS3 mutation carriers. Severe excess mortality in SCN5a increased between the ages of 10 and 14 years, at an SMR of 9.8 and between 20 and 39 years, at an SMR of 3.8. However, after the age of 60 years, no excess mortality was observed. Mortality risk in catecholaminergic polymorphic ventricular tachycardia (CPVT) was highest between the ages of 20 and 39 years, at an SMR of 3.0, and in Brugada syndrome, was highest between the ages of 40 and 59 years, at an SMR of 1.72. “We have to be careful not to draw conclusions for families with arrhythmias caused by different mutations,” said Nannenberg in a press statement. “However, this new data can guide screening. In LQTS1, we advise starting genetic and heart screening of first-degree family members (children, siblings, parents) at a very young age,” he recommended. MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012 Circ Cardiovasc Genet 2012; Advance online publication

Pharmacologic Prevention of Microvascular and Macrovascular Complications in Diabetes Mellitus

Pharmacologic Prevention of Microvascular and Macrovascular Complications in Diabetes Mellitus: Implications of the Results of Recent Clinical Trials in Type 2 Diabetes Authors: Tandon, Nikhil1; Ali, Mohammed K.2; Narayan, K.M. Venkat2 Source: American Journal of Cardiovascular Drugs, Volume 12, Number 1, 1 February 2012 , pp. 7-22(16) Abstract: Observational epidemiologic data indicate that lower blood glucose levels, blood pressure (BP), and lipid parameters are associated with a lower incidence of micro- and macrovascular complications in people with diabetes. While no threshold for this effect is discernible in these observational studies, intervention studies do not mirror this finding. The earliest glycemia target study in type 2 diabetes mellitus, UKPDS, demonstrated unequivocal benefits of tight glucose control on microvascular complications, but needed a prolonged follow-up to demonstrate a benefit on macrovascular outcomes and mortality. Recently, three major studies, ACCORD, ADVANCE, and VADT, evaluated the impact of attaining euglycemia (ACCORD) or near-euglycemia (ADVANCE, VADT) in older patients with diabetes and high cardiovascular (CV) risk. None of these studies, either individually or on pooled analysis, demonstrated any reduction in all-cause or CV mortality, although the meta-analyses revealed 15-17% reductions in the incidence of non-fatal myocardial infarction in those exposed to tight glucose control. A higher mortality was observed in the intensive glucose control arm of ACCORD, resulting in the premature termination of the glucose-lowering component of this study. Also, the occurrence of hypoglycemic episodes (total and major) was significantly higher in the intensive glucose control arm. ADVANCE and ACCORD also had BP-lowering components. While data from ADVANCE demonstrated a benefit of routine use of a combination of perindopril and indapamide, with a decline in all-cause mortality, CV mortality, and new-onset microalbuminuria, reducing systolic BP to <120 mmHg in ACCORD did not result in any incremental benefits over a systolic BP <140 mmHg. A residual CV risk observed in people with diabetes even after low-density lipoprotein (LDL) cholesterol lowering has led to trials evaluating additional therapy with fibric acid derivatives to reduce triglyceride levels. The lipid-lowering arm of ACCORD failed to demonstrate any benefit of add-on therapy with fibric acid derivatives to LDL-lowering treatment with HMG-CoA reductase inhibitors (statins) on vascular outcomes in patients with diabetes. However, data from earlier studies, and also from the subgroup analysis of ACCORD, indicate a probable benefit of adding treatment with fibric acid derivatives to individuals with persistently elevated triglyceride levels despite statin therapy. The most compelling evidence comes from studies assessing the impact of multiple risk factors - glucose, BP, and cholesterol. Studies like the Steno study unequivocally demonstrate the benefit of aggressive control of all three parameters on vascular outcomes in patients with diabetes. In conclusion, attempts to achieve euglycemia in older patients with type 2 diabetes with co-morbidities are not associated with any survival benefit, but may reduce the occurrence of non-fatal CV events. There is a significant risk of major hypoglycemia with this approach, thereby probably limiting its utility to younger patients with new-onset disease. Similarly, lowering systolic BP below 120 mmHg in high CV risk people with diabetes is associated with significant excess adverse events, limiting the utility of such an intervention. However, a clear benefit, which is also cost effective, is observed with strategies for multiple risk-factor control, which should be universally adopted in clinical practice.

Drug Treatment of Hyperuricemia to Prevent Cardiovascular Outcomes: Are We There Yet?

Authors: Gaffo, Angelo L.; Saag, Kenneth G.

American Journal of Cardiovascular Drugs, Volume 12, Number 1, 1 February 2012 , pp. 1-6(6)

Abstract:
Data supporting an association between high levels of serum urate and cardiovascular disease have continued to emerge. Basic science data, small clinical trials, and epidemiologic studies have provided support for the idea of a true causal effect. In this paper, we present evidence about the association between hyperuricemia and selected cardiovascular diseases. Although data generated so far compellingly support pharmacologic urate-lowering therapy in selected cases with high cardiovascular risk, further evidence is necessary before widely advocating this approach to prevent cardiovascular outcomes putatively associated with hyperuricemia.

Ceguera por degeneración macular el efecto protector de la nutrición

La degeneración macular asociada a la edad representa la principal causa de pérdida de la visión en las personas mayores de 60 años. Esta patología se desarrolla en la mácula, la parte central de la retina que permite una visión nítida de los detalles. La visión periférica, por el contrario, permanece intacta.

El primer síntoma suele ser la visión borrosa en el centro del campo visual y la necesidad de más luz para ver. Al avanzar la enfermedad aumenta la porción poco nítida del campo visual y comienza a ser difícil la realización de las tareas diarias.

Aún no se cuenta con una cura para esta patología pero diversos tratamientos frenan el avance de la degeneración macular. El diagnóstico precoz es fundamental ya que la visión perdida no se puede recuperar.

Los nutrientes clave

Los investigadores trabajaron con 4000 hombres y mujeres de 55 a 80 años de edad y analizaron su consumo de los distintos tipos de nutrientes. A continuación cotejaron sus hábitos alimenticios con la posible pérdida de visión a causa de diversas enfermedades, y publicaron sus conclusiones en la revista Ophthalmology.

Los autores notaron que consumir regularmente una buena ingesta de nutrientes en combinación con carbohidratos de bajo índice glucémico (es decir, los que se asimilan lentamente) parece proteger a las personas de la degeneración macular asociada a la edad.

Los nutrientes que resultaron ser más esenciales incluyen a la vitamina C, vitamina E, cinc, luteina, zeaxantina y los famosos ácidos grasos omega-3.

Coffee Drinking Not Linked to Chronic Illnesses

Coffee Drinking Not Linked to Chronic Illnesses

By Kerry Grens

NEW YORK (Reuters Health) Mar 01 - Studies of coffee's links to myriad diseases have provided conflicting results, but a new paper finds coffee drinkers have no higher risk of heart disease, stroke or cancer, and they are less likely to develop type 2 diabetes.

"We do not encourage people to start drinking coffee if they do not enjoy this, but the overall evidence on coffee and health suggests that there is no reason for persons without specific health conditions to reduce their coffee consumption in order to reduce their risk of chronic diseases," said Dr. Rob van Dam of the National University of Singapore, who was not involved in this study.

In some studies, coffee drinking has been tied to an increase in heart disease, cancer, stroke and more. In others, coffee drinking appears benign or even linked to better outcomes.

"There have been conflicting results from previous studies regarding coffee's effect on chronic disease risk depending on the type of disease," said Dr. Anna Floegel, the lead author of the study and an epidemiologist at the German Institute of Human Nutrition Potsdam-Rehbruecke. "That is why we decided to look at different diseases at the same time to estimate the overall health effect of coffee consumption."

The researchers, who published their findings online February 15 in the American Journal of Clinical Nutrition, collected information on coffee drinking habits, diet, exercise and health from more than 42,000 German adults without any chronic conditions.

Nine years later, they found that coffee drinkers and non-drinkers were similarly likely to develop heart disease, stroke, diabetes and cancer.

For instance, 871 out of 8,689 non-drinkers developed a chronic disease, compared to 1,124 out of 12,137 people who drank more than four cups of caffeinated coffee a day -- about 10% in both groups.

"Our results suggest that coffee consumption is not harmful for healthy adults in respect of risk of major chronic diseases," Dr. Floegel told Reuters Health by email.

On the other hand, coffee drinkers were less likely to develop type 2 diabetes. Among those who consumed four cups a day at baseline, 3.2% developed type 2 diabetes, compared to 3.6% of people who drank no coffee. After adjustment for diabetes risk factors, the researchers determined that frequent coffee drinkers were 23% less likely to develop diabetes.

That squares with other studies. "Higher coffee consumption has been consistently associated with a lower risk of type 2 diabetes in many prospective studies across the world," Dr. van Dam said by email (see Reuters Health report of December 14, 2009).

This doesn't mean that coffee is responsible for preventing type 2 diabetes, however. Although the researchers tried to account for other known diabetes risk factors, there could be inaccuracies in measuring these factors and there could be other, unknown influences too, Dr. van Dam said.

However, experiments in animals have hinted that certain chemicals found within coffee could positively affect metabolism, he noted.

The most notorious component of coffee -- caffeine -- is likely uninvolved, because Dr. Floegel's group found that frequent decaf drinkers also had a lower risk of developing diabetes than people who didn't drink any coffee.

Dr. Floegel said she'd like to see future studies dig down into the possible biological explanations for coffee's role in diabetes, and how people who already have diabetes respond to coffee.

Am J Clin Nutr 2012.

Does A Subclinical Cardiotoxic Effect of Clozapine Exist?

Does A Subclinical Cardiotoxic Effect of Clozapine Exist? Results From a Follow-Up Pilot Study; Rostagno C, Domenichetti S, Gensin GF; Cardiovascular & Hematological Agents in Medicinal Chemistry (Feb 2012)

Aim: The aim of the present study was to investigate by serial echocardiography and dosage of NT-pro-BNP, whether, in previously healthy subjects, long term therapy with clozapine may lead to subclinical cardiac toxicity. Methods and Results: 38 patients (24 males, 14 females, mean age 38.4 years) suffering from a severe personality disorder were enrolled. At inclusion duration of clozapine treatment averaged 66 months at a mean daily dose of 296 mg. Clinical evaluation, NT-pro-BNP dosage and echocardiography were performed at baseline, 3 and 12 months. At first visit 15 patients showed depression of left ventricular function (12 had LVEF between 50 and 55%, 2<50%&1<30%). Biventricular dysfunction was observed in 10. NT-pro-BNP showed a significant inverse relation with LVEF (r2= -0.4619, p<0.0001). At 1 year the whole group did not show significant changes in clinical, ECG and echocardiographic measurement, however a LVEF decrease>5% was found in 33% of patients with baseline normal LVEF while LVEF remained below 55% in 70% of group B patients. LVEF and NT-pro-BNP values were still significantly different in the two groups at the term of follow-up. Conclusions: Subclinical heart dysfunction, frequently biventricular, occurs in 1/3 of young, previously healthy, clozapine treated patients. NT-pro-BNP values relate inversely with LVEF. At 1 year follow -up a LVEF decrease>5% occurred in 1/3 of patients with baseline normal left ventricular function.