Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Cholesterol-Lowering Foods Beat Low-Saturated Fat Diet

By Kristina Fiore, Staff Writer, August 23, 2011

Explain that a dietary intervention study of cholesterol-lowering foods with either two or seven counseling sessions significantly lowered LDL cholesterol compared with a control diet emphasizing reduced saturated fat consumption.

Note that the results between the groups receiving two versus seven counseling sessions were not significantly different.
Review
Eating a predominantly vegetarian diet focused on lowering cholesterol -- and getting advice on how to do so effectively -- can drop LDL levels more than a diet focused only on reducing saturated fat, researchers found.

A diet rich in cholesterol-lowering foods dropped LDL by 13% to 14% over six months, depending on the level of accompanying counseling, compared with a drop of just 3% for patients on a control diet, David Jenkins, MD, of St. Michael's Hospital in Toronto, and colleagues reported in the August 24/31 issue of the Journal of the American Medical Association.

"Our data demonstrate the cholesterol-lowering potential of a dietary portfolio intervention that counsels participants to increase consumption of cholesterol-lowering foods denoted by the FDA to have a heart-health benefit," they wrote.

Foods with known cholesterol-lowering properties -- such as nuts, soy, and barley -- have been shown to be effective in lowering serum cholesterol in metabolically controlled conditions, the researchers said.

So they assessed whether eating a diet consisting of these foods decreased LDL cholesterol compared with a control diet that emphasized eating fiber and whole grains.

They enrolled 351 patients with hyperlipidemia at four centers across Canada, who were given one of three diet plans: a "dietary portfolio" that emphasized plant sterols, soy protein, viscous fibers, and nuts with either two counseling sessions or seven sessions over six months, or a control diet focused on lowering saturated fats without counseling. Control patients were not allowed to eat foods in the intervention portfolio, the researchers said.

The 51 patients who were taking statins before the study had discontinued them at least two weeks prior.

Mean LDL cholesterol at baseline was 171 mg/dL.

In the modified intention-to-treat analysis of 345 patients, the researchers saw significant reductions in LDL cholesterol only for patients in both arms of the portfolio diet: a 13.8% reduction for those who had intensive counseling and a 13.1% drop for those with "routine" counseling (P<0.001 for both) compared with a nonsignificant 3% drop for those on the control diet.

Jenkins and colleagues said the LDL reductions were "approximately half those observed with early statin trials, that were associated with 20% reductions in coronary heart disease mortality."

"Further study is needed to determine whether cholesterol reduction using these portfolio components is associated with lower rates of coronary heart disease events," they wrote.

They also noted that more frequent visits to the clinic appear to be unnecessary in achieving significant reductions in LDL. "The near maximal effectiveness of only two clinic visits enhances the suitability of this dietary approach for clinical application," they added.

The portfolio diet also improved the ratio of total cholesterol to HDL cholesterol, dropping 8.2% for the routine counseling and 6.6% for the intensive counseling (P<0.001 for both). Those reductions were significantly greater than those for the control diet, but weren't significantly different from each other, the researchers said.

The cholesterol-lowering diet also reduced the calculated 10-year heart risk by 10.8% for those on routine counseling and by 11.3% for those on intense counseling, which was significantly greater than the nonsignificant 0.5% drop in risk for those on the control diet.

The researchers noted that reductions in LDL were associated with dietary adherence for those on the cholesterol-lowering diet (P<0.001).

"Convincing people to change dietary patterns is difficult, much less convincing them to become vegetarians," Jana Klauer, MD, a primary care physician in New York, said in an email to MedPage Today and ABC News. "But it can be done -- just look at Bill Clinton," noting the former president and heart disease patient who recently became a vegan in order to glean its benefits to lower his cardiovascular risk.

But Merle Myerson, MD, EdD, of St. Luke's and Roosevelt Hospitals in New York, said the counseling component is perhaps the trickiest part.

"Medicare and most insurances do not reimburse for one session of nutrition counseling, unless you have diabetes or end-stage renal disease, much less the kind of patients in this study," she said, adding that she doubts patient adherence would be sufficient in the long run.

The study was limited because the intervention was complex and lipid-lowering effects couldn't be pegged to specific components. Also, they cautioned about its high overall dropout rate of 22.6%, though they noted this is "an attrition rate common to dietary studies at these levels of intensity."

As well, the study may lack generalizability because its population was predominantly white, with low-to-intermediate risk of cardiovascular disease, and may not translate to those with a higher risk of disease.

Still, they concluded that "a meaningful 13% LDL reduction can be obtained after only two clinic visits of approximately 60- and 40-minute sessions."

[Chevychelov]

LV Filling Problems Signal HF Risk

By Crystal Phend, Senior Staff Writer, August 23, 2011

Explain that a longitudinal population-based study found that diastolic dysfunction increased with age and over time and was associated with the development of heart failure.

Note that progression of diastolic dysfunction to a more severe degree was associated with a higher incidence of heart failure.
Review
Worsening left ventricular diastolic function may contribute to heart failure onset, according to a longitudinal population-based study.

Diastolic dysfunction predicted an 81% elevated risk of developing heart failure over four years even after adjustment for the traditional risk factors (HR 1.81, 95% CI 1.01 to 3.48), Richard J. Rodeheffer, MD, of the Mayo Clinic in Rochester, Minn., and colleagues found.

One in four persons with moderate to severe diastolic dysfunction developed heart failure during further long-term follow-up, they reported in the Aug. 24/31 issue of the Journal of the American Medical Association.

Persistence of or progression to more severe problems with left ventricular filling was associated with higher heart failure incidence (P<0.001).

"Although confirmation in other studies would be helpful, our data suggest that persistence or progression to diastolic dysfunction is a risk factor for heart failure in elderly persons," the group wrote in the paper.

They analyzed diastolic findings among 2,042 individuals ages 45 and older (mean 61) examined in the Olmsted County (Minnesota) Heart Function Study.

In a previous study, body fat was linked to left ventricular diastolic dysfunction. In the current study, the mean body mass index at baseline for the 1,402 participants who later had a repeat examination four years later was 28.3, and only one-quarter of them had a BMI less than 25. These numbers did not change at the repeat exam.

However, BMI did not predict LV diastolic dysfunction from exam one to exam two in this cohort. The mean BMI for those who developed LV dysfunction and those who did not was 28.1 kg/m2. The unadjusted odds ratio (OR) was 0.99 (95% CI 0.99 to 1.01), while the OR adjusted for age and sex was 1.0 (95% CI 0.99 to 1.01).

At the repeat examination, researchers found an overall increase in diastolic dysfunction prevalence from 23.8% to 39.2% and in prevalence of moderate to severe cases from 6.4% to 16.0% (both P<0.001).

Further follow-up over 6.3 years linked heart failure onset to worse diastolic function (P<0.001 for trend). The heart failure incidence rates were:
2.6% in those whose diastolic function remained normal or normalized
7.8% in those whose left ventricular diastole became or remained mildly dysfunctional
12.2% in those who progressed to or continued to have moderate to severe diastolic dysfunction


While left ventricular diastolic dysfunction was associated with advancing age, especially once individuals reached 65 (OR 2.85, 95% CI 1.77 to 4.72), diastolic dysfunction wasn't clearly linked to change in systolic function.

Nor were only those with risk factors affected.

Among apparently healthy participants without hypertension, diabetes, coronary artery disease, heart failure, or cardiovascular drug use, prevalence of diastolic dysfunction rose from 11.3% to 29.8% over four years (P<0.001) and 19.9% showed worsening diastolic function over time.

"That diastolic dysfunction worsened even in healthy persons supports the concept that aging may be accompanied by progressive deterioration in diastolic function," Rodeheffer's group wrote in the paper.

"This age-related progression of diastolic dysfunction in the population contributes to the pathophysiologic substrate from which overt heart failure emerges," they added.

The investigators cautioned, though, that their findings may have underestimated the effect of worsening diastolic dysfunction because participants lost to follow-up between examinations were sicker, with worse diastolic dysfunction, and higher mortality rates yielding survival and participation bias.

Generalizability of these findings from a largely white population to other races and ethnicities is not clear, the group added.

[Chevychelov]

FDA Warns Against High-Dose Citalopram

By John Gever, Senior Editor, Reviewed by
August 24, 2011

Review

Citing increased risk of cardiac arrhythmias and a lack of therapeutic benefit associated with high doses of the selective serotonin reuptake inhibitor (SSRI) citalopram hydrobromide (Celexa), the FDA has reduced the recommended maximum to 40 mg/day.

Previously, the agency had approved a 60-mg/day dose of the antidepressant for certain patients.

The new dosing instruction was prompted by postmarketing surveillance reports and a prospective trial linking the 60-mg dose to unacceptable QT interval prolongations and Torsade de Pointes.

The trial -- a randomized, placebo-controlled, crossover study in 119 adults -- examined citalopram's effects on QT intervals at doses of 20 mg and 60 mg, the FDA said.

Relative to the placebo phase, the 20-mg dose produced mean QT prolongation of 8.5 msec (90% CI 6.2 to 10.8). At 60 mg, QT intervals were extended by an average of 18.5 msec (90% CI 16.0 to 21.0).

By interpolating these results, the FDA estimated that a 40-mg dose would prolong QT intervals by an average of 12.6 msec (90% CI 10.9 to 14.3), which it deemed marginally acceptable.

"As a result of this thorough QT study, FDA has determined that citalopram causes dose-dependent QT interval prolongation and should no longer be used at doses above 40 mg per day," the agency said in a drug safety communication.

Congestive heart failure, bradyarrhythmias, and predispositions to potassium or magnesium deficiencies are risk factors for Torsade de Pointes, the FDA noted.

Consequently, the agency recommended that patients with these conditions should undergo regular electrocardiography if given citalopram, and hypokalemia and hypomagnesemia should be corrected before starting patients on the drug.

Patients currently taking citalopram at doses higher than 40 mg/day should not stop the drug abruptly, but should talk to their doctors about lowering the dose, and should seek treatment immediately for irregular heartbeats, shortness of breath, fainting, or dizziness.

Package inserts for citalopram, which is also available in generic forms, will be rewritten to include the new information, the agency said.

The FDA did not indicate that the cardiac effects were an issue with escitalopram (Lexapro), which is the S-enantiomer of citalopram -- suggesting that the arrhythmias stem from the latter's R-enantiomer.

[Chevychelov]

Anticoagulation therapy: New score for hemorrhage risk

Gregory B. Lim
Abstract

A new scoring scheme to predict the risk of warfarin-associated hemorrhage in patients with atrial fibrillation (AF) has been published by researchers from the ATRIA (Anticoagulation and Risk Factors in AF) study group based at Kaiser Permanente in the US. Warfarin is commonly prescribed to patients with AF to reduce the risk of thrombosis, but according to Dr Margaret Fang, lead author of the report, “anticoagulants can significantly reduce a person's risk of AF-related stroke; however, anticoagulants also [confer] significant risks—in particular, an increased risk of bleeding.
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Antithrombotic drug and stent choices in primary PCI
[Ссылки доступны только зарегистрированным пользователям ]

Кого интересует,то что ниже, быстрее забирайте. Пишут, что доступ временный.

Dietary factors associated with hypertension
[Ссылки доступны только зарегистрированным пользователям ]

Managing kidney disease with blood-pressure control
[Ссылки доступны только зарегистрированным пользователям ]

A comprehensive review of the clinical aspects of primary aldosteronism
[Ссылки доступны только зарегистрированным пользователям ]

Prenatal programming—effects on blood pressure and renal function
[Ссылки доступны только зарегистрированным пользователям ]

Blood pressure lowering in patients with diabetes—one level might not fit all
[Ссылки доступны только зарегистрированным пользователям ]

Epidemiology of hypertensive kidney disease
[Ссылки доступны только зарегистрированным пользователям ]

The relationship between blood pressure and cognitive function
[Ссылки доступны только зарегистрированным пользователям ]

The role of Rho protein signaling in hypertension
[Ссылки доступны только зарегистрированным пользователям ]

Novel therapeutic targets for hypertension
[Ссылки доступны только зарегистрированным пользователям ]

Assessment and management of hypertension in children and adolescents
[Ссылки доступны только зарегистрированным пользователям ]

Aldosterone and arterial hypertension
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[Chevychelov]

2011 Safety Alerts for Human Medical Products

Drugs and Therapeutic Biological Products
Product Name Date Issued/Updated
5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer 06/09/2011
Abacavir - Ongoing Safety Review: Possible Increased Risk of Heart Attack 03/01/2011
Acetadote (acetylcysteine) Injection: Recall - Particulate Matter Found in a Small Number of Vials 01/01/2011
Acetaminophen Prescription Products Limited to 325 mg Per Dosage Unit: Drug Safety Communication 01/13/2011
Aidapak Services Repackaged Pharmaceuticals: Recall - Potential Cross Contamination with Beta Lactam Products 06/03/2011
Albuterol Sulfate Inhalation Solution 0.083%, 3 mL Unit Dose Vials: Recall - Mislabeled Unit Dose Vials 01/03/2011
American Regent Injectable Products: Recall - Visible Particulates in Products 07/20/2011
Angiotensin Receptor Blockers (ARBs): Drug Safety Communication - Drug Safety Review Completed 06/02/2011
Antipsychotic drugs: Class Labeling Change - Treatment During Pregnancy and Potential Risk to Newborns 02/22/2011
Avandia (rosiglitazone): REMS - Risk of Cardiovascular Events 05/18/2011
Benzocaine Topical Products: Sprays, Gels and Liquids - Risk of Methemoglobinemia 04/07/2011
Birth Control Pills Containing Drospirenone: Possible Increased Risk of Blood Clots 05/31/2011
Butalbital, Acetaminophen, and Caffeine Tablets (USP 50mg, 325mg, 40mg) and Hydrocodone Bitartrate and Acetaminophen Tablets (USP 7.5mg, 500mg): Recall - Bottle Mislabeled 06/27/2011
CardioGen-82 PET Scan: Drug Safety Communication - Increased Radiation Exposure 07/26/2011
Celexa (citalopram hydrobromide): Drug Safety Communication - Abnormal Heart Rhythms Associated With High Doses 08/24/2011
Chantix (varenicline): Label Change - Risk of Certain Cardiovascular Adverse Events 07/22/2011
Citalopram And Finasteride by Greenstone: Recall - Possible Mislabeling 03/28/2011
Coumadin (warfarin sodium) Crystalline 5 mg Tablets: Recall - Tablets May Have Higher than Expected Potency 05/03/2011
Diflucan (fluconazole): Drug Safety Communication – Long-term, High-dose Use During Pregnancy May Be Associated With Birth Defects 08/03/2011
Endocet (Oxycodone / Acetaminophen) Tablets, ( 10mg, 325mg ) : Recall - Some Bottles Contain Different Strength Tablets 06/27/2011
Erythropoiesis-Stimulating Agents (ESAs) In Chronic Kidney Disease: Drug Safety Communication - Modified Dosing Recommendations 06/24/2011
H & P Industries Povidone Iodine Prep Pads: Recall - Potential Microbial Contamination 03/18/2011
Hydrocodone Bitartrate And Acetaminophen Tablets, Phenobarbital Tablets by Qualitest: Recall - Incorrect Package Labeling 02/07/2011
Indomethacin for Injection: Recall of One Lot - Particulate Matter 06/15/2011
Irinotecan Hydrochloride Injection: Recall - Fungal Microbial Contaminant 03/28/2011
Kaletra (lopinavir/ritonavir): Label Change - Serious Health Problems in Premature Babies 03/08/2011
Lansoprazole Delayed-Release Orally Disintegrating Tablets by Teva Pharmaceuticals: Letter to Healthcare Professionals - Clogged, Blocked Oral Syringes and Feeding Tubes 04/15/2011
Long-Acting Beta-Agonists (LABAs): New Safe Use Requirements 04/15/2011
Meds IV Pharmacy, IV Compounded Products Recall: Outbreak of Serratia Marcescens Bacteremia in Alabama Hospitals 03/30/2011
Methylene Blue: Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications 07/26/2011
Metronidazole Tablets, 250mg: Recall - Underweight Tablets 01/06/2011
Morphine Sulfate Oral Solution 100 mg per 5 mL (20 mg/mL): Medication Use Error - Reports of Accidental Overdose 01/10/2011
Multaq (dronedarone): Drug Safety Communication - Increased Risk of Death or Serious Cardiovascular Events 07/21/2011
Multaq (dronedarone) - Drug Safety Communication: Risk of Severe Liver Injury 01/14/2011
Nature Relief Instant Wart and Mole Remover: Recall - Risk of Severe Skin Burns 06/27/2011
Needleless Pre-filled Glass Syringes: Stakeholder Advisory - Compatibility Problems with Needleless Intravenous Access Systems 05/06/2011
Nulojix (belatacept): Risk Evaluation and Mitigation Strategy (REMS) 07/07/2011
Oral Osteoporosis Drugs (bisphosphonates): Drug Safety Communication - Potential Increased Risk of Esophageal Cancer 07/21/2011
Pradaxa (dabigatran etexilate mesylate) Capsules: Special Storage and Handling Requirements 03/30/2011
Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication - Low Magnesium Levels Can Be Associated With Long-Term Use 03/02/2011
Revlimid (lenalidomide): Ongoing Safety Review - Increased Risk of Developing New Malignancies 04/08/2011
Risperdal (risperidone) and Risperidone: Recall - Uncharacteristic Odor 06/20/2011
Risperidone (Risperdal) and Ropinirole (Requip): Medication Errors - Name Confusion 06/13/2011
Tamiflu (oseltamivir phosphate) for Oral Suspension: Label Change-New Concentration (6 mg/mL) 07/11/2011
Terbutaline: Label Change - Warnings Against Use for Treatment of Preterm Labor 02/17/2011
Topamax (topiramate): Recall - Musty Odor 04/15/2011
Topamax (topiramate): Label Change - Risk For Development of Cleft Lip and/or Cleft Palate in Newborns 03/04/2011
Triad Alcohol Prep Pads, Alcohol Swabs, and Alcohol Swabsticks: Recall Due to Potential Microbial Contamination 06/08/2011
Tumor Necrosis Factor (TNF) blockers, Azathioprine and/or Mercaptopurine: Update on Reports of Hepatosplenic T-Cell Lymphoma in Adolescents and Young Adults 04/14/2011
Tylenol Extra Strength Caplets, 225 count bottles: Recall - Uncharacteristic Odor 06/29/2011
Tysabri (natalizumab): Update of Healthcare Professional Information 04/22/2011
Unapproved Cough, Cold, Allergy Products: FDA Prompts Removal From Market 03/02/2011
Warfarin Sodium Tablets (Jantoven), 3mg: Recall - Mislabeled Bottles Containing Higher Dosage 02/21/2011
Yervoy (ipilimumab): Risk Evaluation and Mitigation Strategy (REMS) - Severe Immune-Mediated Adverse Reactions 04/06/2011
Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy) 06/30/2011
Vasopressin Injection USP, Multiple Dose Vials: Recall - Sub-Potency 08/04/2011
Victoza (liraglutide [rDNA origin]) Injection: REMS - Risk of Thyroid C-cell Tumors, Acute Pancreatitis 06/13/2011
Zocor (simvastatin): Label Change - New Restrictions, Contraindications, and Dose Limitations 06/08/2011
Zyvox (linezolid): Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications 07/26/2011

Special Nutritional and Cosmetic Products
Product Name Date Issued/Updated
SimplyThick: Public Health Notification - Risk of Life-Threatening Bowel Condition 06/05/2011
Multi-Mex Distributor Inc. Dietary Supplements: Recall - Product Packaging Mimics OTC Antibiotics 05/10/2011
Pentrexyl Forte Natural: Recall - Misleading Packaging 05/23/2011
Soladek Vitamin Solution: Unapproved Product May Contain Dangerously High Levels of Vitamins A and D 03/29/2011

[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

24-Hour Monitoring Best to Diagnose Hypertension

By Crystal Phend, Senior Staff Writer, August 24, 2011

Action Points
Explain that this study found that ambulatory blood pressure monitoring is the most cost-effective way to confirm a hypertension diagnosis before starting treatment.


Point out that the American Heart Association recommends home monitoring for newly diagnosed or suspected hypertension with ambulatory monitoring reserved for equivocal cases to help establish the diagnosis.
Review
Ambulatory blood pressure monitoring is the most cost-effective way to confirm a hypertension diagnosis before starting treatment, researchers found.

The cost-savings from avoiding misdiagnosis was greater with ambulatory monitoring than with further blood pressure measurements in the office or at home, Richard J. McManus, MSc, MBBS, of the University of Birmingham, England, and colleagues reported.

Ambulatory confirmation saved from $92 (£56) to $533 (£323) across groups in the modeling study released online in The Lancet.


Moreover, ambulatory monitoring slightly boosted quality-adjusted life years among patients older than 50.

"Ambulatory monitoring for most people before the start of antihypertensive treatment should be seriously considered," McManus' group argued in the paper.

In response, the British regulatory agency that helped fund the study is altering its guidelines to recommend ambulatory monitoring as a best practice.

The National Institute for Health and Clinical Excellence (NICE) announced the change at a press briefing held in London the same day as the Lancet paper was published.

The American Heart Association recommends home monitoring for newly diagnosed or suspected hypertension with ambulatory monitoring reserved for equivocal cases to help establish the diagnosis.

The traditional approach has been two repeat visits for in-office measurement after an initial finding of elevated blood pressure, Thomas A. Gaziano, MD, of Brigham and Women's Hospital in Boston, noted in a commentary accompanying the Lancet study.

That ambulatory monitoring is cost-saving isn't surprising because it addresses the problem of white-coat hypertension, he pointed out.

"Improved diagnosis by both home and ambulatory monitoring results in reduction of morbid or fatal, as well as expensive, events attributable to cardiovascular disease, and minimizes treatment of people who otherwise would be incorrectly labelled hypertensive," Gaziano wrote in the commentary.

The financial savings with ambulatory monitoring compared with home monitoring was likely because the automated ambulatory monitoring device has greater accuracy, suggested Joseph Diamond, MD, director of nuclear cardiology at Long Island Jewish Medical Center in Hyde Park, N.Y.

Whether serially-obtained automated blood pressure measurements could be just as accurate and cost-effective if taken in the office isn't clear, he noted in a statement sent to reporters.

McManus' group modeled cost-effectiveness on a hypothetical primary-care population age 40 and older that screened positive for a blood pressure over 140/90 mm Hg and had hypertension risk factor prevalence similar to the general population.

After accounting for costs associated with equipment, consumables, maintenance, and staff time as well as costs of treatment for hypertension and cardiovascular events, ambulatory monitoring for 24 hours to confirm hypertension diagnosis was less expensive in all gender and age groups than several repeat office visits or home measurements over a week's time.

These savings "were primarily because of the costs of hypertensive treatment that were avoided because of the higher specificity of ambulatory monitoring," the researchers noted.

They pointed to the example of 60-year-old men for whom ambulatory monitoring cost $69 (£42) more per diagnosis but saved $237 (£144) in treatment costs compared with clinic monitoring, while costs for subsequent cardiovascular events and follow-up were similar between groups.

Home monitoring had similar results as office visits for both quality of life and costs across age and gender groups.

Even in the younger age groups for whom ambulatory monitoring was associated with a small reduction in quality-adjusted life years and cost-effectiveness ratios greater than $82,470 (£50,000) per QALY, it remained most cost effective.

The only assumptions that changed the ranking of the three methods were if home monitoring was as accurate as ambulatory testing and if treating people who did not have true hypertension actually reduced their cardiovascular risk.

If repeat screening was done on a yearly rather than every-five-year basis for those who screened negative for hypertension, home monitoring became more cost-effective for younger age groups, although "unrealistic in clinical practice where annual ambulatory monitoring would be judged excessive for most people."

The researchers noted that if they had included small negative effects of treatment side effects in their analysis, the cost-effectiveness of ambulatory monitoring would have looked even better.

The results are likely widely generalizable to primary care, they added, pointing to prior studies from the U.S., Australia, and Italy that found cost savings with ambulatory rather than further in-office monitoring.

[Chevychelov]

Heart Failure Deaths Down in U.S.

By Kristina Fiore, Staff Writer, Reviewed by
August 26, 2011

Review

Death rates in patients hospitalized for congestive heart failure have fallen over the last decade, particularly among the oldest patients, government researchers found.

Between 2000 and 2007, overall mortality rates were cut nearly in half, from 55 to 28 per 1,000 admissions, according to a News and Numbers data brief from the Agency for Healthcare Research and Quality.

Patients 85 and older saw the greatest drop, from 87 to 48 deaths per 1,000 admissions, the researchers found.

"We see [the decline] cutting across all age groups," Ernest Moy, MD, MPH, medical officer for the AHRQ and an author on the report, told MedPage Today. "Older patients still have the highest death rates, but it's also falling."

Mortality rates among patients 65 and up fell from 64 to 34 deaths per 1,000 admissions during the period, and rates among patients ages 45 to 64 fell from 28 to 15 deaths per 1,000 admissions.

For those ages 18 to 44, the decline was from 19 to 12 deaths per 1,000 hospital admissions, the researchers found.

Moy said the declines are statistically significant: "We believe they are real, that hospitals are taking better care of patients," he said.

Yet he noted that disparities appear to exist between urban and rural hospitals, with greater declines in mortality rates for patients seen in metropolitan facilities than for those in smaller cities.

"It's a little disconcerting," Moy said. "Over time, it's been falling, but it's still an area of concern."

The researchers also saw that rates fell slightly more for patients with Medicare rather than private insurance, and rates for private insurance were still higher than those for Medicare patients in 2007 (35.6% versus 26.9%).

Moy said that patients who develop heart failure before they're eligible for Medicare may indicate that they have a more serious form of the condition, which may explain why death rates for those with private insurance are higher.

The findings are part of the 2010 National Healthcare Disparities Report, which assesses disparities in access to and quality of healthcare in the U.S.

From the American Heart Association:
Updates in HF and CAD
Heart Disease and Stroke 2011 Statistical Update

Primary source: Agency for Healthcare Research and Quality
Source reference:
2010 National Healthcare Quality & Disparities Report

[Chevychelov]

Early Preeclampsia Triples Risk of Hypertension

By Charles Bankhead, Staff Writer,
Published: August 26, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points
Explain that a study of cardiovascular risk factors 10 years after pregnancy showed that women who had preeclampsia before 32 weeks gestation had more than triple the risk of hypertension compared with controls who had a pregnancy without preeclampsia.


Note that meeting criteria for metabolic syndrome and waist circumference were also increased in those with a history of preeclampsia.
Preeclampsia before 32 weeks of gestation more than tripled a woman's odds of hypertension before age 40, a study of cardiovascular risk after preeclampsia showed.

Women who had developed preeclampsia had significantly higher mean systolic and diastolic blood pressure 10 years later than a matched control group of women who did not have preeclampsia, according to an article published online in the European Journal of Cardiovascular Prevention & Rehabilitation.

Women with a history of preeclampsia also had a twofold greater prevalence of metabolic syndrome. Waist circumference, too, was significantly greater in the preeclampsia group, which had a numerically greater body mass index (BMI).

Lipids, glucose, and C-reactive protein levels did not differ between women who had a history of preeclampsia and those who did not.

"The etiology of preeclampsia is as yet unresolved," Jose T. Drost, MD, of Isala Clinics in Zwolle, the Netherlands, and co-authors wrote in conclusion.

"Research on genetics and metabolic biomarkers is needed for a better understanding of its pathogenesis. Additional research should focus on the cost-effectiveness of cardiovascular screening programs and the timing of treatment of cardiovascular risk factors in women with previous preeclampsia."

Several studies have demonstrated associations between preeclampsia and future cardiovascular disease (CVD), and the magnitude of the association appears related to the severity of metabolic disturbances caused by preeclampsia.

Although the etiology of preeclampsia remains largely undetermined, early-onset preeclampsia (before 32 weeks of gestation) has a different pathophysiology than preeclampsia later in pregnancy, the authors wrote in their introduction.

Early preeclampsia induces an inflammatory response in the maternal circulation, leading to vasoconstriction and activation of the thrombotic cascade in the mother. Placental lesions associated with preeclampsia resemble early atherosclerosis, the authors continued.

In most cases, preeclampsia symptoms dissipate within a few weeks. However, decades later, women with a history of preeclampsia have at least a twofold greater risk of CVD.

Data from intermediate follow-up of women with a history of preeclampsia are scant, resulting in an uncertain time frame during which CVD risk factors develop. The lack of data is especially pertinent to the subgroup of women who develop the condition early in pregnancy, who might be targeted for early prevention.

Drost and colleagues sought to examine the emergence of CVD risk factors in women 10 years after an episode of early preeclampsia, defined as diastolic blood pressure ≥90 mmHg accompanied by proteinuria ≥0.3 g/24 h occurring before 32 weeks of gestation.

The study population consisted of women who responded to a mailed questionnaire and invitation to participate in a cardiovascular screening program. The investigators subsequently recruited 339 women with a history of early preeclampsia and 332 age-matched women with uncomplicated pregnancies.

Baseline characteristics included a mean age of 39 and mean interval of nine to 10 years since childbirth. Offspring of the preeclampsia group had a significantly lower mean birth weight (about 3.2 lbs versus 7.5 lbs, P<0.05), and the preeclampsia group had a significantly higher rate of stillbirth (14.8% versus 3.9%, P<0.05).

As compared with the control group, women with a history of early preeclampsia had significantly higher mean blood pressure (127/86 versus 119/79 mmHg, P<0.001 for systolic and diastolic pressure) and waist circumference (86.5 versus 83.2 cm, P=0.001) and a trend toward higher BMI (26.9 versus 26.2, P=0.066).

The authors reported that 43.1% of the preeclampsia group had hypertension (≥140/90 mmHg) as compared with 17.2% of the control group. The difference translated into an odds ratio of 3.5 for the preeclampsia group (P<0.001).

Fewer than half of the hypertensive women received adequate antihypertensive therapy (20.6% in the preeclampsia group versus 2.1% in the control group, P<0.05).

Twice as many women with a history of preeclampsia met diagnostic criteria for metabolic syndrome (18% versus 9%), resulting in an odds ratio of 2.18 (P=0.002).

No other clinical or metabolic parameters differed significantly between groups.

The authors cautioned that their findings cannot be extrapolated to women after 32 weeks of gestation with preeclampsia. There also may have been some bias as the women with preeclampsia were more motivated to participate than the controls, researchers said.

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ESC: Anticoagulants Top Meeting Agenda

By Todd Neale, Senior Staff Writer,
Published: August 26, 2011

PARIS -- The ARISTOTLE trial pitting the novel anticoagulant apixaban against warfarin for preventing stroke in patients with atrial fibrillation looks like it will be the stand-out of this year's meeting of the European Society of Cardiology here.

The top-line results -- which were reported by Bristol-Myers Squibb and Pfizer in June -- showed that apixaban, a direct factor Xa inhibitor, was as effective as warfarin at preventing stroke and systemic embolism in patients with arrhythmia.

"We got a hint that this is a positive trial and we're really looking forward to this because the new anticoagulants are the next wave of therapy in afib," according to Christopher Cannon, MD, a cardiologist at Brigham and Women's Hospital in Boston and Editor-in-Chief of CardioSource.

Cannon previewed some of the trials via webcam in an exclusive interview with MedPage Today.

Some of the other highlights include a subanalysis of the ROCKET-AF trial looking at the use of rivaroxaban to prevent stroke in patients with atrial fibrillation and renal dysfunction and another of the RE-LY trial examining the use of dual antiplatelet therapy in patients taking dabigatran (Pradaxa) or warfarin.

Attendees will also hear results from the PRODIGY trial, which compared six months versus 24 months of dual antiplatelet therapy following PCI, and the dal-VESSEL trial, which evaluated the safety and efficacy of the novel CETP inhibitor dalcetrapib.

Overall, there are 27 presentations scheduled for three Hot Line sessions and two Clinical Trial Update sessions.

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Calcium Scans Pick Up Controversy in Cardiology

By Crystal Phend, Senior Staff Writer,
Published: August 26, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Action Points
Note that the state of Texas has enacted legislation which mandates insurance coverage for imaging tests, such as noncontrast CT scans, for CVD screening in men between 45 and 75 years and women ages 55 to 75 years with intermediate risk or greater.

Point out that over 2 million people in Texas would be eligible for screening with a projected one time cost of almost $500 million. Also point out that there are no randomized clinical trials demonstrating improved outcomes from imaging screening and that CT studies carry a potential risk from radiation-induced cancer.

Coronary artery calcium scans might be the best thing since sliced risk scores or the worst example of "medicine gone wild," garnering strong and divisive opinions in cardiology.

The noncontrast CT screening test is vying for a role in determining which otherwise low- to moderate-risk patients may need more aggressive cardiovascular prevention.

When news broke last week of a study in The Lancet suggesting that calcium scans predicted risk of cardiovascular events better than high-sensitivity C-reactive protein (CRP) in a relatively healthy population like that in the JUPITER trial, major networks carried breathless statements about the technology:
"Before you go on a cholesterol medication, I want you to ask your doctor about this: A coronary artery calcium test." -- Dr. Richard Besser on ABC
"Unless you do the imaging, you are really playing Russian roulette with your life." -- Dr. Arthur Agatston in a CNN report

While these reports were criticized in Forbes and the healthcare media watchdog Health News Review, some leading cardiologists find themselves just as impressed by coronary artery calcium screening.

"There are so many different agendas we can view this with; there's no surprise this is not something that has uniform vision from all the individuals involved," he explained in an interview with MedPage Today.

Calcium Scores for Risk Reclassification

Statin therapy guided by traditional risk factors enumerated in the Framingham risk score, which uses age, gender, cholesterol, smoking status, and blood pressure, can provide an important first step in prediction but leaves much to be desired. The estimated risk is based on population data.

The high-risk population by traditional factors clearly needs lifestyle intervention and consideration of a statin medication, and calcium score won't change that decision making.

But persistent rates of heart attack and other events in the intermediate- and low-risk groups suggest that traditional factors are missing important clues of impending danger.

Calcium scanning has looked good in studies reclassifying risk.

In one large cohort study published in the Journal of the American College of Cardiology earlier this year, calcium score independently predicted 25% elevated risk of coronary events and 12% elevated risk of death from any cause.

It improved prediction by 23.8% over what Framingham score, body mass index, and known cardiovascular disease could do compared with a 10.5% improvement by high-sensitivity CRP.

Based on results like these, the American Heart Association updated its guidelines in 2010 to call calcium scans "reasonable" in intermediate-risk patients, putting it on par with echo screening of carotid intima-medial thickness (IMT).

The Society for Heart Attack Prevention and Eradication now recommends calcium and carotid IMT scans for all intermediate-risk people ages 45 to 80 and for men 35 and older who are diabetic or have a family history of premature coronary disease.

Another advantage of coronary scans, according to some reports, is their power for patient motivation.

Calcium scores moved patients to get to work on their heart disease risk factors -- reducing blood pressure, LDL cholesterol, and waist circumference compared with patients who didn't get the scan, another JACC study reported in March.

A meta-analysis in the Archives of Internal Medicine suggested that noninvasive imaging may not be very motivating for physicians to change prescribing.

But "you'd be surprised how if you tell a 55-year-old that his cholesterol is 260, he's going to look at you and go 'Okay, yeah, I know that's high,'" Weintraub said. "However, if you tell a 55-year-old he has the arteries of a 75-year-old, that tends to get his attention."

Not Just a Simple Test

Calcium scanning got all the wrong kind of attention initially from many physicians.

"There has been a lot of controversy around calcium scoring because most of the early proponents owned their equipment and had a huge conflict of interest," William W. O'Neill, MD, chief medical officer of the University of Miami Health System, noted in an email to MedPage Today and ABC News.

High-sensitivity CRP has faced the same concern, with the pivotal JUPITER trial of statins in lower-risk, high-CRP patients led by a patent holder on the CRP blood test, Paul Ridker, MD, MPH, of Brigham and Women's Hospital in Boston.

Also, "many of us were initially bothered by the way calcium scanning was introduced, as a for-profit test marketed directly to the community, without good evidence to support its use," de Lemos explained in an email.

Calcium scans, generally, aren't reimbursed by insurance, with the exception of coverage mandated by a 2009 Texas state law. The average out-of-pocket cost runs about $100 elsewhere.

Recent studies have redeemed the test in many minds, but there's still no randomized trial showing that coronary artery calcium-guided therapy leads to better outcomes, de Lemos noted.

But no screening method has such large-scale clinical trial evidence, noted Amit Khera, MD, MSc, a cardiologist at UT Southwestern.

The widely used Framingham risk score hasn't been tested in a randomized trial. Even CRP, for which the randomized JUPITER trial demonstrated benefit of treating patients with high CRP as their sole risk factor, doesn't have gold standard evidence since JUPITER didn't include a low CRP arm.

"What we need from our imaging colleagues are trial data, not assumptions of what might work without formal evaluation," Ridker argued in an email to MedPage Today.

"Remember, the imaging community also assumed for years that statins would reduce coronary artery calcium scores, but when trials were finally done this turned out to be a completely wrong assumption," he noted.

The lack of change in calcium score with treatment can be troubling to some physicians and patients, Weintraub noted.

And that often leads to unnecessary catheterization and stenting, "so actual costs to the healthcare system are very high," added Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic, who called calcium scanning "one of the worst examples of 'medicine gone wild'" in an email to MedPage Today and ABC News.

Incidental findings are a well-known concern with CT imaging, including when imaging coronary arteries for calcium.

Radiation, too, is an issue.

One calcium scan confers the equivalent of 10 chest X-rays or two mammograms, which could be expected to result in cancer in nine per 100,000 persons tested, according to an analysis done by Khera at the time the Texas law passed.

Though one-third the radiation a person gets on average from the sun and environment are offset by a potential reduction in cardiovascular deaths, the cancer risk is important when talking about asymptomatic individuals, Khera noted.

"In the absence of evidence, why use a test that is associated with radiation, cost, and leads to a number of downstream consequences instead of a simple panel of blood tests along with data on age, smoking, and blood pressure?" Ridker questioned in an email.

Competition or Collaboration?

Yet it may not be an either-or situation between calcium scanning and other noninvasive screening methods.

In the JACC cohort study that showed incremental predictive power of calcium scoring, its combination with high-sensitivity CRP had better discriminatory power than either measure alone.

"I think ultimately it's going to be a combination of things," Weintraub told MedPage Today. "We've known for a long time that CRP and calcium scores don't necessarily coincide."

Calcium in the arteries points to stable plaque, while inflammatory markers like high-sensitivity CRP indicate vulnerability of plaque to rupture, he noted.

Carotid IMT images the coronary arteries with ultrasound, eliminating the radiation concerns, and may be particularly useful for risk prediction in younger people in whom the calcium score is likely to be zero.

Some evidence also suggests carotid IMT is a better predictor of stroke risk, whereas calcium score may be a better predictor of coronary events, Khera noted.

So which test or combination of tests you choose may depend to some degree on the individual patient, he suggested.

"We're in the sorting out period right now," he told MedPage Today. "The positive is these are all potential new tools that can be used, and they all have some value. It's just figuring out how to use each test and where they should be used and what to do about them."

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ESC: Hot Line Sizzles Even When Data Are Not So New

By Peggy Peck, Executive Editor, Published: August 27, 2011

PARIS -- By the numbers, the European Society of Cardiology meeting is the largest cardiology meeting in the world -- more than 30,800 registrants, representing 154 countries, who will have the opportunity to hear and see findings from 4,276 studies.

But at an opening press conference the meeting organizers all agreed that most of the interest here is focused on the results of a single study -- ARISTOTLE -- that will take center stage Sunday during a Hot Line plenary session.

The results of the trial, which compared the investigational factor Xa inhibitor, apixaban (Eliquis), against warfarin for prevention of stroke in patients with atrial fibrillation, will not surprise anyone because two months ago the two companies that developed the drug, Bristol-Myers Squibb and Pfizer, reported positive top-line data in a press release.

In the U.S., organizations like the American College of Cardiology and American Heart Association typically don't include trials that have had a pre-release of data as breaking clinical trials. For example, when results of the ENHANCE trial, a study of ezetimibe/simvastatin (Vytorin) versus simvastatin were released at a company press conference two months before the ACC's annual meeting, ENHANCE was not included in the ACC's breaking clinical trial line-up, but was instead presented during a separate plenary session.

But that early release was not viewed as a problem by the ESC because, as Michael Böhm, MD, PhD, of University Hospital of Saarland, Homburg, Germany, told MedPage Today, those top-line data did not include "important details" that will be presented during the Hot Line presentation. Since the companies presented only scant information, the ESC decided that the full results met its criteria for presentation, explained Böhm, who chairs the ESC program committee.

And in any event, Böhm, ESC President Michel Komajda, MD, of Pitié Salpetrière Hospital in Paris, and ESC's communication chairman, Kurt Huber, MD, director of cardiology at Wilhelminen Hospital in Vienna, all agreed that ARISTOTLE was a study too good to pass up for the ESC meeting.

Not that there was any paucity of material for the program committee to choose as 10,836 abstracts were submitted, Böhm said, with most of them coming from Japan. However, the country with the most accepted abstracts was Germany with 514 papers. U.S. researchers, by contrast, are reporting 201 papers here, but one of those accepted abstracts was ARISTOTLE.

Komajda said this year's meeting will also feature results from 15 registries, data that he said reflect real-world findings.

The ESC meeting continues through Wednesday.

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ESC: Guideline Issued to Treat CVD in Pregnancy

By Todd Neale, Senior Staff Writer,
Published: August 27, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Action Points
Explain that the European Society of Cardiology has released guidelines for the management of cardiovascular disease during pregnancy, although most of the recommendations are based on small studies, retrospective data, registries, expert consensus, or a combination.

Point out that the guidelines recommend pre-pregnancy risk assessment and counseling in all women with known or suspected congenital or acquired cardiovascular and aortic disease.

PARIS -- Despite a dearth of prospective, randomized data, the European Society of Cardiology has released guidelines for the management of cardiovascular disease during pregnancy.

Because of the lack of evidence, most of the recommendations are classified as level C, meaning that they are based on small studies, retrospective data, registries, expert consensus, or a combination.

They were crafted by the ESC's task force on the management of cardiovascular diseases during pregnancy -- chaired by Vera Regitz-Zagrosek, MD, of Charité Universitaetsmedizin Berlin -- and published online in the European Heart Journal before the start of the society's annual meeting here. The guidelines will be formally introduced later in the meeting.

Even though a small fraction of pregnancies in developed countries -- 0.2% to 4% -- are complicated by cardiovascular diseases, "knowledge of the risks associated with cardiovascular disease during pregnancy and their management are of pivotal importance for advising patients before pregnancy," the authors wrote.

They added that heart disease is the leading cause of maternal death during pregnancy.

Regitz-Zagrosek and colleagues noted that the guidelines come at a time when the risk of cardiovascular disease in pregnant women is growing as a result of increasing age at first pregnancy and higher rates of diabetes, hypertension, and obesity.

Also contributing are improvements in the treatment of congenital heart disease, which allows more women to reach reproductive age. In western countries, congenital heart disease accounts for 75% to 82% of cases of cardiovascular disease during pregnancy.

There are particular considerations surrounding the treatment of cardiovascular disease in pregnant women, according to the authors, because of the physiological changes that occur during gestation.

Pregnancy leads to increased blood volume and cardiac output; reductions in systemic vascular resistance and blood pressure; and a higher risk of thromboembolic events. In addition, some changes affect the absorption, excretion, and bioavailability of medications.

The guidelines detail screening for heart disease in pregnant women, assessing risk, and counseling.

Although there are multiple methods for assessing the risk of cardiovascular events in pregnant women, the authors recommended using the World Health Organization risk classification, which takes into account all known maternal cardiovascular risk factors, including underlying heart disease and comorbidities.

According to this system, as risk increases, so does the frequency of the recommended follow-up visits during pregnancy. The guidelines state, however, that women at the highest risk should be advised against pregnancy altogether. If pregnancy occurs, termination should be discussed, but if gestation continues, the woman should be followed monthly or bimonthly, the authors wrote.

Contraindications to pregnancy in this classification include:
Pulmonary arterial hypertension of any cause
Severe systemic ventricular dysfunction
Previous peripartum cardiomyopathy with any residual impairment of left ventricular function
Severe mitral stenosis
Severe symptomatic aortic stenosis
Marfan syndrome with the aorta dilated more than 45 mm
Aortic dilatation greater than 50 mm in aortic disease associated with bicuspid aortic valve
Native severe coarctation


The guidance includes both general recommendations and more specific advice for certain groups -- those with congenital heart disease, aortic disease, valvular heart disease, coronary artery disease and acute coronary syndromes, cardiomyopathies and heart failure, arrhythmias, hypertensive disorders, or venous thromboembolism.

The class I general recommendations (all level C evidence) are as follows:
Pre-pregnancy risk assessment and counseling is indicated in all women with known or suspected congenital or acquired cardiovascular and aortic disease.
Risk assessment should be performed in all women with cardiac diseases of childbearing age and after conception.
High-risk patients should be treated in specialized centers by a multidisciplinary team.
Genetic counseling should be offered to women with congenital heart disease or congenital arrhythmias, cardiomyopathies, aortic disease, or genetic malformations associated with cardiovascular disease.
Echocardiography should be performed in any pregnant patient with unexplained or new cardiovascular signs or symptoms.
Before cardiac surgery, a full course of corticosteroids should be administered to the mother whenever possible.
The same measures used in non-pregnant patients should be used in pregnant patients for the prevention of infective endocarditis.
Vaginal delivery is recommended as the first choice in most patients.

The single class III (level C) general recommendation advises against the use of prophylactic antibiotic therapy during delivery.

The guidelines conclude with a section on the use of cardiovascular drugs during pregnancy and breastfeeding, although there are no specific recommendations regarding treatment.

"In case of emergency, drugs that are not recommended by the pharmaceutical industry during pregnancy and breastfeeding should not be withheld from the mother," the authors wrote. "The potential risk of a drug and the possible benefit of the therapy must be weighed against each other."

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Apixaban Prevents Strokes, Boosts Survival in Afib Patients

This report is part of a 12-month Clinical Context series.By Peggy Peck, Executive Editor
Published: August 28, 2011
Reviewed by Michael Mullen, MD; Clinical Instructor of Vascular Neurology, University of Pennsylvania.

PARIS -- Compared with warfarin treatment, atrial fibrillation patients treated with the investigational factor Xa inhibitor apixaban had fewer strokes or embolic events, fewer major bleeding events, and were less likely to die during an average of almost two years of treatment, researchers said.

Those results emerged from the 18,201-patient ARISTOTLE study, which was published online today by the New England Journal of Medicine.

"The primary outcome of stroke or systemic embolism occurred in 212 patients in the apixaban group (1.2% per year) as compared with 265 patients in the warfarin group (1.60% per year)," Christopher B. Granger, MD, of the Duke Clinical Research Institute at Duke Action Points
Explain that apixaban, an oral factor Xa inhibitor, was compared to dose adjusted warfarin in subjects with atrial fibrillation.


Note that in the primary outcome of hemorrhagic or ischemic stroke or systemic embolization, apixaban was superior to warfarin.


Note that apixaban had a lower rate of major bleeding and a lower rate of death from any cause than warfarin.
University Medical Center in Durham, NC, and colleagues wrote.Action Points
Explain that apixaban, an oral factor Xa inhibitor, was compared to dose adjusted warfarin in subjects with atrial fibrillation.

Note that in the primary outcome of hemorrhagic or ischemic stroke or systemic embolization, apixaban was superior to warfarin.

Note that apixaban had a lower rate of major bleeding and a lower rate of death from any cause than warfarin.

Additionally, the hazard ratio in the apixaban group was 0.79 (95% CI 0.66 to 0.95; P<0.001 for noninferiority and P=0.01 for superiority.

The benefit was largely driven by the difference in hemorrhagic stroke -- 0.24% per year for apixaban (40 strokes) versus 0.47% (78 strokes) for warfarin (HR 0.51, 95% CI 0.35-0.75, P<0.001). The rate of ischemic stroke was similar in both arms of the trial, 0.9% per year with apixaban and 1.05% per year with warfarin (P=0.42).

The authors concluded that the lower risk of hemorrhagic stroke "suggests there is a specific risk associated with warfarin, possibly related to its inhibition of multiple coagulation factors or interaction between warfarin and tissue factor VIIa complexes in the brain."

The median age of patients in ARISTOTLE was 70, and all had at least one additional risk factor for stroke. About a fourth of the patients were treated at centers in North America and 40% were treated at European centers. The rest of the clinical sites were in South America or the Asian Pacific.

Background therapies included ACE inhibitors or ARBs in about 70% of patients, as well as beta-blockers (63-64%), statins (45%), and aspirin (31%). About 41% of patients had normal creatinine clearance, and 42% had mildly impaired creatinine clearance.

The 9,120 patients in the apixaban arm received 5 mg bid (2.5 mg in selected patients) while warfarin patients were treated to target (international normalized ratio [INR], 2.0 to 3.0). Blinding was assured with sham INR testing in the apixaban arm.

On average the warfarin patients had INRs in therapeutic range 62% of the time.

In addition to publication in NEJM, the ARISTOTLE results were reported at the European Society of Cardiology meeting during a Hot Line session today.

Asked about the results, Elliott Antman, MD, professor of medicine at Harvard Medical School, and a spokesperson for the American Heart Association, called the trial results "not only a home run, but an out of the park home run."

Indeed, when compared with the other emerging oral agents -- dabigatran (Pradaxa), which is FDA approved for stroke prevention in patients with atrial fibrillation, and rivaroxaban (Xarelto), which is approved for prevention of DVT in patients undergoing joint replacement surgery -- apixaban does have some advantages.

For example, rivaroxaban, which is also a direct factor Xa inhibitor, demonstrated that it was not inferior to warfarin, but there was not proof of superiority to warfarin in ROCKET-AF. And a pivotal trial that compared dabigatran with warfarin found higher rates of myocardial infarction, gastric distress, and dyspnea among patients treated with dabigatran.

But in an NEJM editorial, Jessica L. Mega, MD, MPH, of Harvard Medical School in Boston, wrote that dabigatran (150 mg bid) is the only one of the three agents to have "significantly reduced the risk of ischemic stroke compared with warfarin."

Mega noted that a third direct factor Xa inhibitor (edoxaban) is currently being tested in the ENGAGE study, which is being conducted by her colleagues at Brigham and Woman's Hospital (including Antman, who is the principal investigator for that study).

Nonetheless, she wrote that warfarin is unlikely to be swept away by the new agents because although it does require INR monitoring and dietary restrictions -- it easily beats any of competitors on cost, estimated at $4.00 a month compared with as much as $160/month for dabigatran.

Ralph Brindis, MD, a cardiologist at Kaiser Permanente in Oakland, Calif., and immediate past president of the American College of Cardiology, said the ARISTOTLE results were "just another stake or dagger in the heart of warfarin for prevention stroke."

He said, however, that as good as the apixaban numbers were, they won't necessarily translate into a big win when -- or if -- the FDA approves the drug.

A potential downside of these new drugs is that it is not possible to monitor adherence. No need for blood tests could make the drugs very appealing to patients, but for clinicians that is not necessarily the case since "one of the strengths of warfarin is that we know the patient is adhering because we are getting the blood tests," he explained.

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SATURN Statin Trial a Dead Heat

By John Gever, Senior Editor, September 02, 2011

Review

Rosuvastatin (Crestor) failed to beat atorvastatin (Lipitor) for improving atheroma volume in a large head-to-head trial, the drug's manufacturer reported.

AstraZeneca issued a terse statement outlining the top-line results of the trial.

"The results for the primary efficacy measure, which was change from baseline in percent atheroma volume in a ≥40 mm segment of the targeted coronary artery as assessed by intravascular ultrasound (IVUS), demonstrated a numerically greater reduction in favor of Crestor versus atorvastatin but did not reach statistical significance," the statement said.

The two-year SATURN study compared 40 mg/day of rosuvastatin to 80 mg/day of atorvastatin in some 1,300 patients.

However, the company said, rosuvastatin treatment did lead to a significantly greater reduction in the trial's secondary efficacy measure, total atheroma volume within the targeted coronary artery.

AstraZeneca's statement did not give numerical results. It said the data and interpretations would be presented at the American Heart Association's scientific meeting in November.