Latest Research

October 19, 2007

A summary of the "must-read" articles from the journals in that pile on your desk.

Mixed Views on Coronary Disease Treatment Trial

Detractors question value of percutaneous coronary intervention

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial did not provide evidence of benefit from percutaneous coronary intervention plus medical therapy versus medical therapy alone, according to a report in the Oct. 16 issue of the Journal of the American College of Cardiology. However, an editorial in the same issue questions this view.

Dean J. Kereiakes, M.D., of the Lindner Research Center in Cincinnati, and colleagues conclude that the COURAGE trial set unrealistic goals for reduction in annual rates of death and myocardial infarction as a result of using percutaneous coronary intervention in addition to drugs to treat chronic stable angina pectoris. The authors, many of whom have financial ties to drug companies, also conclude that the findings of the trial found no benefit to invasive treatment versus drug therapy alone.

But in an accompanying editorial, George A. Diamond, M.D., and Sanjay Kaul, M.D., of the University of California Los Angeles, assert that the trial's detractors missed the new information generated by the COURAGE trial that could help in the management of stable coronary disease.

They concur that the trial findings indicate no particular advantage to an initial recommendation of percutaneous coronary intervention plus optimal medical therapy, but add that the trial shows "percutaneous coronary intervention can be reserved for a later time with little risk that an unfavorable event will intervene."

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Hospice a Seldom Used Option in Heart Failure Patients

Only 1.6 percent in sample went from hospital to hospice; referred patients more likely to be older

Although a number of consensus statements and guidelines support palliative care for patients with advanced heart failure, only a small number of patients admitted to acute care hospitals for decompensated heart failure are referred to hospice, according to research published in the Oct. 8 issue of the Archives of Internal Medicine.

Paul J. Hauptman, M.D., of the Saint Louis University School of Medicine, and colleagues analyzed data on 182,898 episodes of acute decompensated heart failure from 307 hospitals in order to assess patient and hospital variables associated with hospice referral.

The investigators found that only 1.6 percent of patients were referred to hospice. Hospitals that most commonly referred patients to hospice adhered to quality indicators for heart failure at least as well as hospitals that were least likely to refer patients to hospice, indicating that patients weren't discharged excessively early.

"Several publications have proposed indications for hospice referral in patients with heart failure. Hospice care under Medicare is appropriate for patients deemed to have a likely six-month life expectancy by their physician and the hospice medical director. Guidelines for hospice referral recommend that the patient should demonstrate severe limiting symptoms and poor prognosis despite optimal medical therapy or documentation of intolerance to therapy," the authors write.

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Diabetic Platelet Reactivity Increases Cardiovascular Risk

Risk higher in patients with coronary artery disease on anti-platelet therapy

Patients with type 2 diabetes mellitus and coronary artery disease chronically treated with anti-platelet therapy are at higher risk of major cardiovascular events if they have high platelet reactivity, according to a report published online Oct. 1 in the Journal of the American College of Cardiology.

Dominick J. Angiolillo, M.D., Ph.D., from the University of Florida College of Medicine--Shands Jacksonville, and colleagues measured platelet activation and aggregation in 173 patients with type 2 diabetes and coronary artery disease who were on chronic treatment with aspirin and clopidogrel.

During two years of follow-up, there were 41 major adverse cardiovascular events in 34 patients (19.7 percent). High platelet reactivity was the strongest independent predictor of major adverse cardiovascular events, with a cutoff of 62 percent of maximal platelet aggregation being the best predictor (hazard ratio 3.35). Patients with high platelet reactivity had significantly increased activation of multiple platelet signaling pathways, according to the study.

"High platelet reactivity determined in type 2 diabetes mellitus patients with coronary artery disease while on chronic dual anti-platelet therapy is associated with a higher risk of long-term adverse cardiovascular events, suggesting the need for tailored anti-thrombotic drug regimens in these high-risk patients," Angiolillo and colleagues conclude.

Angiolillo is a speaker and consultant for Aventis, Bristol-Myers Squibb and Eli Lilly and has received an award sponsored by GlaxoSmithKline Research.

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Several Factors May Contribute to Methemoglobinemia

Rare complication can follow use of topical benzocaine anesthetic in transesophageal echocardiography

Acquired methemoglobinemia, a rare complication of the use of benzocaine anesthetic, may occur more often in patients with systemic infection or anemia, according to research published in the Oct. 8 issue of the Archives of Internal Medicine.

Garvan C. Kane, M.D., Ph.D., and colleagues at the Mayo Clinic College of Medicine in Rochester, Minn., reviewed 19 cases of methemoglobinemia out of 28,478 transesophageal echocardiography (TEE) procedures, which were preceded with topical benzocaine spray. The investigators compared these cases to a control group of 190 TEE patients who didn't develop this life-threatening problem, in which excessive methemoglobin can't bind oxygen, leading to tissue hypoxia.

The researchers found that subjects were significantly more likely than controls to have anemia at the time of TEE (84.2 percent versus 44.7 percent). In addition, 68.4 percent of subjects had evidence of active systemic infection, compared to 6.8 percent of controls, and 63.2 percent of subjects were receiving gastric acid suppression therapy at the time of TEE, compared to 37.9 percent of controls.

"Clinical factors associated with the development of methemoglobinemia include sepsis, anemia and hospitalization. Minimizing or avoiding the use of benzocaine in these patients is recommended," the authors conclude.

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Renal Artery Calcium Increases Hypertension Risk

Risk is independent of cardiovascular disease risk factors

People free of cardiovascular disease who have calcium in their renal arteries, a marker of atherosclerotic plaque burden, have a 60 percent higher risk of hypertension, according to a report published online Oct. 1 in the Journal of the American College of Cardiology.

Matthew A. Allison, M.D., from the University of California at San Diego, and colleagues examined the association between renal artery calcium and hypertension in 1,435 subjects without clinical cardiovascular disease.

The researchers found that 17.1 percent of subjects overall had calcium in either renal artery, with a significantly higher prevalence in men. After adjusting for traditional coronary heart disease risk factors and extent of calcium in the systemic vasculature, the risk of hypertension was significantly higher in subjects with any renal artery calcium (odds ratio 1.61).

"The results of this study suggest that the presence of renal artery calcium is associated with higher odds for prevalent hypertension, independent of cardiovascular disease risk factors and the extent of calcified atherosclerosis in the nonrenal vasculature," Allison and colleagues conclude.

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External Counterpulsation Therapy Effective in Angina

Also effective in patients with heart failure

Enhanced external counterpulsation (EECP) therapy, which consists of sequential compression and decompression of the lower extremities, is safe and effective in patients with stable angina and heart failure, according to a review published in the Oct. 16 issue of the Journal of the American College of Cardiology.

Aarush Manchanda, M.D., from the George Washington University in Washington, D.C., and Ozlem Soran, M.D., from the University of Pittsburgh Medical Center, reviewed the literature regarding the use of EECP therapy in patients with heart failure and in patients with stable angina.

The researchers note that clinical trials have shown that EECP is safe and effective for patients with refractory angina, with average clinical response rates of 70-80 percent that are sustained for up to five years.

The researchers note that EECP can improve symptoms and decrease long-term morbidity by mechanisms including improvement in endothelial and ventricular function, improvement in oxygen consumption, promotion of collateralization, regression of atherosclerosis and peripheral training effects similar to exercise.

"Enhanced external counterpulsation therapy is a valuable outpatient procedure providing acute and long-term relief of anginal symptoms and improved quality of life among a group of patients with symptomatic ischemic heart disease with or without congestive heart failure," the authors conclude.

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Antioxidants Don't Prevent Macular Degeneration

Dietary and supplemental antioxidants no help in primary prevention of age-related macular degeneration

Antioxidants such as vitamins A, C and E, and carotenoids are not effective in the primary prevention of age-related macular degeneration (AMD), according to the results of a meta-analysis published online Oct. 8 in BMJ.

Elaine Chong, of the University of Melbourne in Victoria, Australia, and colleagues conducted a systematic review and meta-analysis of studies evaluating dietary and/or supplement antioxidants for the primary prevention of age-related macular degeneration.

Pooling data from nine prospective cohort studies involving 149,203 people and 1,878 incident cases of AMD, the researchers showed that vitamins A, C and E, zinc, lutein, zeaxanthin, α carotene, β carotene, β cryptoxanthin and lycopene had minimal or no effect in the primary prevention of AMD. Three randomized clinical trials also showed no benefit in AMD prevention.

"There is insufficient evidence that antioxidant supplements prevent the onset of AMD. Cigarette smoking remains the only widely accepted modifiable risk factor for the primary prevention of AMD, and patients seeking advice on AMD prevention should be encouraged to stop smoking," the authors conclude.

Two authors are on the advisory boards of Pfizer and Novartis and have received grants and honoraria from the companies.

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Benefits of Anti-Soft Drink Campaign Diminish Over Time

Year-long intervention reduced overweight and obesity in youths, but effect not sustained two years later

A year-long program promoting a healthy diet and discouraging soft-drink intake in children aged 7 to 11 helped reduce rates of overweight and obesity, but these benefits were not sustained after a two-year follow-up, according to a report published online Oct. 8 in BMJ.

Janet James, health promotion specialist nurse at the Royal Bournemouth Hospital in Bournemouth, U.K., and colleagues conducted a three-year follow-up of the Christchurch obesity prevention project in schools (CHOPPS) program that encouraged healthy diets and discouraged carbonated drinks at six schools in southwest England. The year-long program produced a significant reduction in the number of children aged 7 to 11 becoming overweight or obese.

Two years after the end of the intervention, the researchers obtained measurements from 434 of the original 644 children who participated in the school-based dietary intervention. The proportion of children who were overweight increased in both the original intervention group and the control group, with a body mass index increase of 1.88 in the intervention group and an index increase of 2.14 in the control group.

"The original project provided hope that a simple intervention could be beneficial in preventing obesity, but our new results show no effect two years after the end of the intervention," the authors write. "It remains unclear whether specific interventions or those that focus on all aspects of the diet and physical activity are the most successful."

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Kids' Weight Maintenance Plans Less Effective Over Time

Programs successful compared to control for four months, less encouraging over years

Weight-maintenance programs helped children control their weight over a four-month period following weight-loss treatment, although these effects waned over long-term follow-up, according to research presented in the Oct. 10 Journal of the American Medical Association.

Denise Wilfley, Ph.D., of Washington University School of Medicine in St. Louis, and colleagues examined data from 150 overweight children, aged 7 to 12 years, who underwent a five-month, family-based weight-loss treatment. Following the weight-loss period, the children were randomized to either a control group, or one of two maintenance programs: one with a cognitive-behavioral approach, and one focusing on building healthy peer networks and targeting social issues. Primary outcomes were BMI z scores and percentage overweight.

Children in either intervention maintained their relative weight better than the control group during the interventions. These effects dwindled over the long-term follow-up (two years following randomization), but the effects of the social intervention, either alone or measured with the behavioral program, were significantly better than the control group in terms of BMI z score outcomes from baseline to the two-year follow-up.

According to the authors of an accompanying editorial, "These findings suggest that obesity treatment will likely require ongoing long-term maintenance therapy of some form to be optimally successful."

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Topiramate Shows Promise for Alcoholism

Drug is safe and consistently effective

Topiramate is a safe and effective means to treat alcohol dependence, according to a report published in the Oct. 10 issue of the Journal of the American Medical Association.

Bankole A. Johnson, M.D., Ph.D., of the University of Virginia in Charlottesville, and colleagues conducted a 14-week, double-blind, placebo-controlled trial of 371 men and women aged 18 to 65 years who were diagnosed with alcohol dependence, of whom 183 were randomized to receive up to 300 mg a day of topiramate, and 188 to receive placebo.

In the topiramate group, there was a 8.44 percent difference in the reduction of heavy drinking days compared with the placebo group. However, the topiramate group experienced more adverse outcomes, such as paresthesia, taste perversion, anorexia and problems concentrating.

"Because topiramate pharmacotherapy can be paired with a brief intervention deliverable by non-specialist health practitioners, a next step would be to examine its efficacy in community practice settings," the authors write.

The medication and funding of the clinical trial were provided by Ortho-McNeil Janssen. All authors served on the advisory board for topiramate.

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Vaccine Reduces Impact of Pneumonia in Elderly

Vaccinated patients less likely to die, be admitted to intensive care

Patients with community-acquired pneumonia have a 40 percent lower risk of mortality and intensive care unit admissions if they have been previously vaccinated with 23-valent polysaccharide pneumococcal vaccine, according to study findings published in the Oct. 8 issue of the Archives of Internal Medicine.

Jennie Johnstone, M.D., of the University of Alberta in Edmonton, Canada, and colleagues analyzed data on 3,415 adults with community-acquired pneumonia, of whom 46 percent were female, 62 percent had severe pneumonia and 22 percent had previously been vaccinated with polysaccharide pneumococcal vaccine.

In all, 624 patients were admitted to intensive care or died, including 73 of the 760 vaccinated patients (10 percent) and 551 of the 2,655 unvaccinated patients (21 percent). Whereas only two vaccinated patients (1 percent) were admitted to the intensive care unit, 349 (13 percent) of the unvaccinated patients needed intensive care.

"Although the totality of published evidence to date indicates that pneumococcal vaccination does not prevent community-acquired pneumonia, our results are consistent with the possibility that pneumococcal vaccination leads to better outcomes in those who go on to eventually develop pneumonia," the authors conclude. "Our results further emphasize the importance of adopting adult pneumococcal vaccination guidelines, particularly since only 22 percent of our population were vaccinated before their hospitalization."

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Surgeon Volume Explored in Survival After Breast Cancer

Patients of low-volume surgeons more likely to die, but of causes other than breast cancer

Breast cancer patients who are treated by high-volume surgeons live longer than breast cancer patients who are treated by low-volume surgeons, but not because they are less likely to die from breast cancer, researchers report in the Oct. 8 issue of the Archives of Internal Medicine.

Ann Butler Nattinger, M.D., of the Medical College of Wisconsin in Milwaukee, and colleagues analyzed data on 12,216 women, aged 66 or older, whose stage I or II breast cancers had been operated on by 1,856 surgeons. Cause of death and surgeon volume were determined through death certificate sources and Medicare claims, respectively. Median follow-up was 50 months.

Patients operated on by high-volume surgeons were substantially less likely to die of causes other than breast cancer (relative risk 0.86). Patients of high-volume surgeons were slightly younger on average, more likely to be white, more likely to live in more affluent areas, and more likely to be treated at high-volume hospitals. They also had lower levels of comorbidity and had smaller tumors.

"It is possible that the beneficial effect of high surgeon volume on breast cancer mortality has been overstated," the authors conclude. "Future studies should further evaluate this possibility and rigorously consider whether selection bias could account for volume-outcome relationships for other health concerns."

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Disparities Found Between Medicaid, Commercial Patients

Care for Medicaid enrollees lags in different types of managed care programs

Enrollees in Medicaid managed-care programs receive a poorer quality of health care than those in commercial managed-care programs, based on a variety of quality indicators, researchers report in the Oct. 10 issue of the Journal of the American Medical Association.

Bruce E. Landon, M.D., of Harvard Medical School in Boston, and colleagues compared data from 383 health plans, divided between commercial-only, Medicaid/commercial and Medicaid-only plans. The investigators considered 11 quality-of-care indicators, such as immunizations and screenings, chronic disease management measures and care for pregnant women.

Performance on these measures for Medicaid enrollees was similar whether they were in a Medicaid-only plan or a commercial plan also serving the Medicaid populations. Performance was also similar for commercial enrollees, regardless of whether the program served commercial populations only or a mix of commercial and Medicaid enrollees. However, the performance for the commercial population was better than for the Medicaid population on all but one measure (chlamydia screening). These differences between the two groups were even found within the same health plans.

"Neither mainstreaming of Medicaid beneficiaries in commercial plans nor relying on Medicaid-only plans seems to raise the quality of care to the level experienced by commercial populations. Additional resources will need to be devoted to designing and implementing specific interventions to improve the quality of care for Medicaid beneficiaries enrolled in managed care," the authors write.

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Job Strain After First MI Linked to Future Heart Problems

High demands, low decision latitude play role in doubled risk of future coronary heart disease

People who return to work after a first heart attack and deal with chronic job-related strain face an increased risk of recurrent coronary heart disease events, according to research published in the Oct. 10 issue of the Journal of the American Medical Association.

Corine Aboa-Eboule, M.D., Ph.D., of the Centre Hospitalier Affilie Universitaire de Quebec in Canada, and colleagues analyzed data from a prospective cohort of 972 men and women aged 35 to 59. The investigators interviewed subjects shortly after they returned to work, then again two and six years later. They categorized job strain into four groups, based on whether subjects faced high or low demands on the job, and whether they had high or low decision-making latitude.

Job strain was an independent predictor of recurrent coronary heart disease (hazard ratio 2.00) at 2.2 years and beyond, even after adjusting for 26 potential confounders.

The authors suggest one explanation for the findings could be "a direct effect of job strain via an increased activation of the sympathetic and the renin-angiotensin-aldosterone systems contributing most likely to an accentuated inflammation of the arterial wall and subsequently to the formation of thrombosis." Another, which they deem unlikely, is that "there is an indirect effect of job strain on recurrent coronary heart disease, mediated by a lack of adherence to a healthier lifestyle and drug therapy."

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Ventricular Dyssynchrony Predicts Remodeling

Predicts remodeling at six months with a high sensitivity and specificity

Left ventricular dyssynchrony measured soon after an acute myocardial infarction can predict left ventricular remodeling at six months with a high specificity and sensitivity, according to study findings published online Oct. 1 in the Journal of the American College of Cardiology.

Jeroen J. Bax, M.D., Ph.D., from Leiden University Medical Center in the Netherlands, and colleagues examined factors predicting left ventricular remodeling in 178 patients with acute myocardial infarction who underwent primary percutaneous coronary intervention.

The researchers found that 20 percent of patients underwent left ventricular remodeling at six months. As measured by speckle-tracking radial strain analysis, left ventricular dyssynchrony was a superior predictor of remodeling at six months, with a sensitivity of 82 percent and a specificity of 95 percent using a cutoff value of 130 ms.

"Left ventricular dyssynchrony immediately after acute myocardial infarction predicts left ventricular remodeling at six-month follow-up," Bax and colleagues conclude.

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Intestinal Function Altered in Patients with Heart Failure

Morphology, permeability and absorption altered

Patients with chronic heart failure have altered intestinal morphology, permeability and absorption, according to the results of a study published online Oct. 1 in the Journal of the American College of Cardiology.

Noting that bacterial endotoxin in the intestine may contribute to the inflammation observed in patients with chronic heart failure, Stefan D. Anker, M.D., Ph.D., from Charite in Berlin, Germany, and colleagues compared gut morphology and function in 22 patients with chronic heart failure and 22 control subjects.

The researchers found that the bowel wall thickness in patients with heart failure was significantly higher in the terminal ileum, ascending colon, transverse colon, descending colon and sigmoid. These patients also had a 35 percent increase in small intestinal permeability, a 210 percent increase in large intestinal permeability, a 29 percent decrease in D-xylose absorption, and higher concentrations of bacteria in their mucus.

"Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability and absorption are modified," Anker and colleagues conclude. "Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition."

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Hypoplastic Heart Syndrome Highly Heritable

Leading cause of infant death due to cardiovascular malformation

Hypoplastic left heart syndrome (HLHS), a leading cause of infant death due to cardiovascular malformation, is highly heritable, according to research published online Oct. 1 in the Journal of the American College of Cardiology.

D. Woodrow Benson, M.D., Ph.D., and colleagues from Cincinnati Children's Hospital Medical Center, performed electrocardiograms on 235 members of 38 families with an HLHS proband.

The researchers found that all probands had aortic valve hypoplasia and dysplasia. More than one individual was affected in 55 percent of families and 36 percent of subjects had cardiovascular malformation. The heritability of HLHS alone was 99 percent and with cardiac malformation was 74 percent.

"The high heritability of HLHS suggests that it is determined largely by genetic factors," Benson and colleagues conclude. "The frequent occurrence of left- and right-sided valve dysplasia in HLHS probands and the increased prevalence of bicuspid aortic valve in family members suggests that HLHS is a severe form of valve malformation."

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Paclitaxel Beneficial in HER2-Positive Breast Cancer

Additive therapy benefits women with node-positive breast cancer who are HER2 positive, but not those who are HER2 negative

In women with node-positive breast cancer, those expressing human epidermal growth factor receptor type 2 (HER2) appear to benefit from the addition of paclitaxel after adjuvant treatment, regardless of estrogen-receptor status, according to study findings published in the Oct. 11 issue of the New England Journal of Medicine.

Daniel F. Hayes, M.D., of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues studied 1,500 women treated with doxorubicin and cyclosphosphamide who were randomly assigned to receive either four cycles of paclitaxel or observation.

The researchers found that HER2-positive women who received paclitaxel had a significantly lower risk of cancer recurrence (hazard ratio, 0.59). But they found that the addition of paclitaxel was of no benefit in women with HER2-negative, estrogen-receptor-positive cancers.

"Hayes and his coauthors caution us not to change clinical practice on the basis of their retrospective analysis, but oncologists have a responsibility to their patients to be aware of this report," states the author of an accompanying editorial. "A similar trial of doxorubicin plus cyclophosphamide followed by paclitaxel involving 3,100 patients was published by the National Surgical Adjuvant Breast and Bowel Project in 2005. The results showed a small benefit in five-year disease-free survival but no difference in overall survival as a result of the addition of paclitaxel in women with estrogen-receptor-negative or estrogen-receptor-positive disease."

Several authors report receiving consulting fees from Bristol-Myers Squibb and Abbott.

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Deficits Seen in Quality of Care Delivered to Children

On average, children in the study received less than half of indicated measures in ambulatory care

Children face similar deficits as adults in the quality of the ambulatory care they receive, according to a report published in the Oct. 11 issue of the New England Journal of Medicine.

Rita Mangione-Smith, M.D., of the University of Washington Child Health Institute in Seattle, and colleagues obtained written consent from the parents of 1,536 children to obtain two years of medical records.

Overall, the researchers found children received 46.5 percent of indicated care, which is similar to the rate previously observed for adults (54.9 percent). The investigators also found that children received 67.5 percent of indicated care for acute medical problems, 53.4 percent of indicated care for chronic medical conditions, and 40.7 percent of indicated preventive care.

"Improvement of the performance of the children's health care system will require systemwide change; entreaties to hard-working and deeply caring pediatricians, family physicians, nurses and hospital staff to work harder and care more will not succeed by themselves," state the authors of an accompanying editorial. "Effecting change will require leadership across all levels and systems involved in children's health care and a wholehearted commitment by those who deliver care, pay for care and receive care. Leaders must recognize that the current system does not meet children's needs and must take action."

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Statin Treatment Shows Long-Term Benefits

Pravastatin study supports early intervention and extended treatment in men with high cholesterol

In men with high cholesterol, early treatment with pravastatin may significantly reduce the 10-year risk of death, according to study findings published in the Oct. 11 issue of the New England Journal of Medicine.

Ian Ford, Ph.D., of the University of Glasgow in the U.K., and colleagues analyzed follow-up data for 10 years after completion of a trial that had randomized 6,595 men with high cholesterol and no history of heart attack to receive either pravastatin or placebo for five years.

The cardiovascular benefits associated with pravastatin in the initial trial persisted during the 10-year follow-up period. The risk of death from coronary heart disease or non-fatal myocardial infarction was significantly lower in the pravastatin group than in the placebo group (11.8 percent versus 15.5 percent), despite the fact that both groups had similar rates of statin use after trial completion.

"The data from Ford and colleagues provide some tantalizing insights," the author of an accompanying editorial writes. "The fact that the group originally assigned to pravastatin had better outcomes, even after years of similar statin treatment of the placebo group during the post-trial period, suggests the importance of duration of therapy in determining outcome. Earlier initiation of therapy appears to have durably mitigated the atherosclerotic process."

This study was partially supported by Bristol-Myers Squibb and Sankyo.

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Bacterial Colonization May Predict Childhood Asthma

Neonates who are colonized by certain types of bacteria more likely to develop asthma by age 5

In neonates, colonization of the hypopharyngeal region with certain types of bacteria may predict the development of recurrent wheeze and asthma in early childhood, researchers report in the Oct. 11 issue of the New England Journal of Medicine.

Hans Bisgaard, M.D., of Copenhagen University Hospital in Copenhagen, Denmark, and colleagues obtained and cultured hypopharyngeal samples from 321 asymptomatic infants at age 1 month and followed them until age 5.

The researchers found that neonatal colonization with one or more of three organisms -- Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae -- was associated with persistent wheeze (hazard ratio, 2.40), acute severe exacerbation of wheeze (HR, 2.99) and hospitalization for wheeze (HR, 3.85). When the children were age 5, the researchers found that neonatal colonization was associated with a higher prevalence of asthma (33 percent versus 10 percent) and the reversibility of airway resistance after Beta-2 agonist administration (23 percent versus 18 percent).

The author of an accompanying editorial writes, "In my opinion, the data presented by Bisgaard and colleagues may be interpreted to suggest that bacterial colonization of the hypopharynx in the first four weeks of life indicates a defective innate immune response very early in life, which promotes the development of asthma."

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Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com)