HHAL MEDICAL NEWS JUNE 2010

Adverse Events Associated with Testosterone Administration

ABSTRACT

Background Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.

Methods Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.

Results A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load.

Conclusions In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.

http://consumer.healthday.com/Article.asp?AID=640242

Intensive Glucose Control Reduces Some Microvascular Complications — At the Cost of Increased Mortality

Intensive glucose control in high-risk diabetes offers mixed results, according to two new analyses from the ACCORD trial.

In ACCORD, patients with type 2 diabetes and elevated cardiovascular risk were randomized to intensive glucose control or standard therapy. About half were also assigned to intensive or standard blood pressure control, and the other half to combination or standard lipid therapy. Intensive glucose control was stopped early, in 2008, because of increased mortality.

Now, writing in the Lancet, ACCORD researchers report that the glucose-control groups did not differ in composite outcomes measuring kidney function, diabetic eye complications, andperipheral neuropathy. However, several components of the composite outcomes (e.g., microalbuminuria, cataract extraction) were less common with intensive glucose control.

And in the New England Journal of Medicine, ACCORD researchers observe that both intensive glucose control and combination lipid th­­­­­­­­­­­erapy reduced progression of retinopathy, while intensive BP control did not.

Despite the microvascular benefits, the Lancet authors conclude, the increased mortality makes aggressive hemoglobin targets in high-risk diabetes seem "imprudent."

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60576-4/abstract

Albuminuria and Glomerular Filtration Rates as Independent Predictors of Mortality

Data will help refine the stages of chronic kidney disease.

Albuminuria and estimated glomerular filtration rate (eGFR) are used to define stages of chronic kidney disease, but at what levels such stage transitions occur continues to be debated. In this analysis, researchers combined patient-level data from 21 large population-based studies (1.2 million patients) that provided data on baseline albuminuria or eGFR and on outcomes, including all-cause or cardiovascular mortality. In the three largest studies, dipstick testing was used to measure albuminuria, but urine albumin-to-creatinine ratios (ACRs) were available for more than 100,000 patients.

Mortality risk was fairly constant for eGFR between 75 and 105 mL/minute/1.73 m². In contrast (with eGFR of 95 mL/minute/1.73 m² as a baseline), hazard ratios for all-cause mortality were 1.18, 1.57, and 3.14 for eGFRs of 60, 45, and 15 mL/minute/1.73 m², respectively. Compared with mortality at a baseline ACR of 5 mg/g, HRs for all-cause mortality were 1.20, 1.63, and 2.22 for ACRs of 10, 30, and 300 mg/g, respectively. Dipstick measurement of albumin yielded results that were similar to those obtained by ACR; cardiovascular mortality risk mirrored that for all-cause mortality. The association of eGFR with all-cause mortality was similar across all levels of ACR and vice versa, suggesting multiplicative independent risk factors; results were largely independent of other cardiovascular risk factors.

Comment: These data will be helpful in refining the stages of chronic kidney disease, perhaps including greater importance for higher levels of albuminuria. Inclusion of renal parameters also could sharpen the precision of cardiovascular risk calculators.

http://www.ncbi.nlm.nih.gov/pubmed/20483451?dopt=Abstract

Type 2 diabetes can be prevented
Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of Type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs. (Free registration required.) The Lancet

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60746-5/abstract

More Evidence Against Rosiglitazone

Rosiglitazone continues to compare unfavorably with other diabetes therapies in two studies released online Monday.

Updating their 2007 meta-analysis, researchers again found that rosiglitazone significantly increased the risk for myocardial infarction, while there was no increase in risk for cardiovascular or all-cause mortality. The update appears in the Archives of Internal Medicine.

Writing in JAMA, researchers present their analysis of cardiovascular and mortality risks in a retrospective cohort of over 200,000 Medicare patients. The subjects had started treatment with either rosiglitazone or pioglitazone and were followed for up to 3 years (median, 105 days). Compared with patients taking pioglitazone, those on rosiglitazone had higher risks for stroke,heart failure, and death. Risk for MI did not differ between the groups. The authors calculate a number needed to harm of 60 patients treated for 1 year.

JAMA's editorialist suggests as one option the "removal of rosiglitazone from the US market." (In July, FDA advisors will meet to discuss whether to keep the drug on the market.)

http://archinte.ama-assn.org/cgi/content/full/2010.207

Archives' Studies Call into Question Statins for Primary Prevention

Two papers in the Archives of Internal Medicine cast doubt on the benefits of statins for primary prevention.

In a meta-analysis, researchers combined data from 11 placebo-controlled trials of statin use in some 65,000 high-risk patients without cardiovascular disease at baseline. During nearly 4 years of treatment, LDL levels were lower in statin than in placebo users (mean, 94 vs. 134 mg/dL) — but there was no difference in all-cause mortality. Editorialists say the analysis "makes it clear that in the short-term, for true primary prevention, the benefit, if any, is very small."

In another paper, investigators took a closer look at the JUPITER trial, in which rosuvastatin reportedly lowered cardiovascular risk by 50% among patients without heart disease or hypercholesterolemia but with high C-reactive protein. The investigators say the trial was "flawed" — it was stopped too early, data on cardiovascular mortality were lacking, and more than half the researchers had financial ties to industry. Accordingly, they conclude: "The results of the trial do not support the use of statin treatment for primary prevention."

http://archinte.ama-assn.org/cgi/content/full/170/12/1024

Early Dialysis Not Necessarily Better in Chronic Kidney Disease

In patients with chronic kidney disease, outcomes are similar regardless of the planned timing of dialysis, according to a New England Journal of Medicine study.

Researchers in Australia and New Zealand randomized some 830 adults with progressive, end-stage renal disease to early initiation of dialysis (when estimated glomerular filtration ratereached 10-14 ml/minute) or late initiation (eGFR, 5-7 ml/minute). Ultimately, dialysis began an average of 5.5 months earlier in the early-start group. About three-fourths of "late-start" patients actually began dialysis when eGFR was above 7 ml/minute, owing to symptoms such as uremia.

During a median 3.5 years' follow-up, mortality was similar in the two groups (about 35%). In addition, there were no differences in cardiovascular outcomes, infections, or dialysis complications.

The authors say their findings show that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7.0 ml per minute or more traditional clinical indicators for the initiation of dialysis are present."

http://content.nejm.org/cgi/content/full/NEJMoa1000552

Digoxin Associated with Higher Mortality in Patients on Dialysis

Digoxin use in patients on hemodialysis is associated with increased mortality, according to aretrospective cohort study in the Journal of the American Society of Nephrology.

Among some 120,000 patients starting hemodialysis in a 6-year period, digoxin use was associated with a 28% increased risk for death. Higher serum level of digoxin, but not the dosage prescribed, was also associated with increased mortality. For patients with high serum digoxin levels, lower potassium levels at the outset of dialysis therapy (under 4.3 vs. over 4.6 mEq/L) were associated with the greatest risk.

The increased risks remained significant after adjustment for disease severity, propensity for treatment, and other characteristics.

The authors recommend "strict [potassium] and digoxin level management" when patients with end-stage renal disease remain on digoxin.

http://jasn.asnjournals.org/cgi/content/abstract/ASN.2009101047v1

Rice Intake and Risk for Developing Type 2 Diabetes

Substituting brown rice for white rice might lower relative risk for diabetes.

Brown rice retains the outer bran and germ that are stripped off to make white rice; the glycemic index (a measure of blood glucose response) of brown rice is lower than that of white rice. Rice intake in the U.S. is almost 21 pounds per person annually, and 70% of that amount is white rice. Harvard investigators pooled data from three U.S. prospective cohort studies to assess the difference in risk for developing type 2 diabetes with brown or white rice intake.

Nearly 200,000 adults without known diabetes, cardiovascular disease, or cancer were assessed at baseline and every 2 to 4 years thereafter (follow-up, 14–22 years). About 10,500 incident cases of diabetes were identified. In adjusted analyses, relative risk for developing diabetes was 17% greater in the group with the highest intake of white rice ( 5 servings weekly) than in the lowest-intake group (<1 serving monthly); conversely, relative risk was 11% lower in the group with the highest intake of brown rice than in the lowest-intake group.

Comment: Diabetes associated with white rice intake has been explored in Asian populations and now has been evaluated for the first time in Western populations.Whole grains in the diet protect against developing diabetes, and brown rice is no exception. We should encourage patients to substitute brown rice for white rice in their diets.

http://www.ncbi.nlm.nih.gov/pubmed/20548009?dopt=Abstract

Stroke Risk Grows with Waistlines in U.S. Women

According to U.S. survey data, rising obesity is associated with rising midlife stroke rates in women, but not in men.

Towfighi A et al. Stroke 2010 May 27;

Hamburgers, Hot Dogs, and Heart Health

In a meta-analysis of observational data, consumption of processed meat conferred higher risks for coronary heart disease and diabetes than consumption of unprocessed red meat.

Micha R et al. Circulation 2010 Jun 1; 121:2271

Is Fast Food Associated with Increasing Asthma Prevalence?

More-frequent burger consumption is associated with a higher prevalence of wheezing in children; consumption of fish, fruit, and vegetables might be protective.

Nagel G et al. Thorax 2010 Jun 65:51

90% of Americans Consume Too Much Sodium

Less than 10% of Americans meet recommendations for daily sodium consumption, according to an article in MMWR.

Using NHANES data, CDC researchers analyzed dietary recall surveys from nearly 4000 adults. Among those whose recommended sodium intake was less than 1500 mg/day (i.e., those who have hypertension, are 40 years or older, or are black), only 5.5% met that target. All other adults had a target of less than 2300 mg/day, yet only 18.8% of them met that target.

The researchers note that healthcare providers can help patients design strategies for reducing sodium in their diet.

(Editor's note: The MMWR report was based on sodium recommendations from the 2005 Dietary Guidelines for America. However, the 2010 version, released last week, recommends the <1500 mg/day target for the general population.)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5924a4.htm

Diabetes Associated with Doubling of Risk for Cardiovascular Events

Adults with diabetes face twice the risk for cardiovascular events as those without diabetes, according to a Lancet meta-analysis.

Using an international research database, analysts combined data on nearly 700,000 adults from some 100 studies that provided information on diabetes status and vascular outcomes. At baseline, 7% of participants had diabetes; no participant had previous vascular disease.

During a median 11 years' follow-up, there were almost 53,000 cardiovascular events, including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and other vascular deaths. Subjects with diabetes had roughly twice the risk for any of these outcomes as those without diabetes. Among people without diabetes, fasting glucose concentrations above 5.6 mmol/L also increased the risk.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60484-9/fulltext­­­­

Long-Acting Exenatide Associated with Better Hemoglobin-Based Diabetes Control

Exenatide, given in once-weekly injections, showed better control of glycated hemoglobin and led to lower weight in type 2 diabetes than treatment with insulin glargine. The study was conducted by the manufacturer and published in the Lancet.

Researchers randomized 450 patients with poorly controlled type 2 diabetes to a 26-week supplemental treatment regimen of either once-weekly injections of long-acting exenatide or daily injections of insulin glargine. By week 8, glycated hemoglobin levels showed greater mean reductions in the exenatide group — a difference that remained for the rest of the study. By 26 weeks, the absolute reductions were 1.5% for exenatide and 1.3% for glargine. In addition, weight loss was greater with exenatide, whereas the glargine group showed progressive weight gain.

Adverse events were more common with exenatide, including a significant increase in mean heart rate.

Editorialists call the results a "small step forward," and, with the authors, call for caution in interpreting the findings.

­­­­­­­­­­­­http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60406-0/fulltext­­­­­­­­­­­­­

Steroid Dosage and Route in Patients Admitted for Chronic Obstructive Pulmonary Disease

Oral low-dose use was associated with less treatment failure than was high-dose parenteral use.

Patients admitted for chronic obstructive pulmonary disease (COPD) usually receive systemic steroids, which have been associated with better outcomes in several priorrandomized trials, but the best dose is still in question. Several major clinical practice guidelines recommend low-dose oral steroids.

In a retrospective cohort study, based on data from 414 U.S. hospitals, Massachusettsinvestigators compared outcomes in nearly 80,000 patients admitted for COPD to non–intensive care unit settings. About 74,000 received parenteral steroids (equivalent to a median dose of 600 mg of prednisone total for the first 2 days), and the rest received oral prednisone (median, 60 mg for the first 2 days). Treatment failure — defined as need formechanical ventilation after the first 2 days, death, or readmission for COPD within 30 days — occurred in 11% of all patients.

In analyses adjusted for about 50 clinical and demographic variables, as well as propensity scores, treatment failure was 16% lower in patients who received oral low-dose steroids than in those who received parenteral steroids; length of stay and cost were about 10% lower in the low-dose group.

http://www.ncbi.nlm.nih.gov/pubmed/20551406?dopt=Abstract

Hypoglycemia and pneumonia: Another mortality indicator
In a population-based sample of patients with community-acquired pneumonia, spontaneous admission hypoglycemia was independently associated with increased mortality during hospitalization that persisted to one year. Patients with hypoglycemia are an easily identified group that may warrant more intensive inpatient and postdischarge follow-up.The Ameri

http://www.amjmed.com/article/S0002-9343(10)00107-5/fulltext

can Journal of Medicine 

Study links NSAID use to increased heart risk in healthy people
Healthy individuals who use nonsteroidal anti-inflammatory drugs to manage minor pain appear to have the same kind of increased heart risk as people with cardiovascular disease, Danish researchers reported in Circulation: Cardiovascular Quality and Outcomes. The finding appears to be consistent with a 2007 scientific statement from the American Heart Association about a relationship between NSAID use and a higher risk of heart attack and stroke.

http://health.usnews.com/health-news/family-health/heart/articles/2010/06/08/common-pain-relievers-raise-heart-risk-for-healthy-folks_print.html

Which arthritis relief drug causes less gastro damage?
Risk of clinical outcomes throughout the gastrointestinal tract was lower in patients treated with a COX-2-selective (Cyclo-oxygenase) NSAID (nonsteroidal anti-inflammatory drugs) than in those receiving a nonselective NSAID plus a PPI (proton-pump inhibitor). These findings should encourage review of approaches to reduce risk of NSAID treatment.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60673-3/abstract

Diclofenac 'Exerts the Same Risk' for Cardiovascular Events as Rofecoxib

Diclofenac (e.g., Voltaren), the widely used nonsteroidal anti-inflammatory agent, "exerts the same risk for cardiovascular adverse events as rofecoxib," according to a Danish study published in Circulation: Cardiovascular Quality and Outcomes. (Rofecoxib [Vioxx] was removed from the market in 2004.)

Using national databases, investigators identified a cohort of over 1 million healthy individuals aged 10 and older. Over a 9-year period, the investigators tracked the subjects' use of NSAID therapy within 30 days of a major cardiovascular event.

Use of the nonselective NSAID diclofenac was associated with an almost twofold increased risk for cardiovascular death (odds ratio, 1.91); in comparison, the odds ratio with rofecoxib was 1.66. There was a dose-dependent increase in risk. Both ibuprofen and naproxen showed increased stroke risk, although naproxen had the safest overall risk profile.

Acknowledging the limitations of their observational study, the authors conclude that their findings expose "a major public health issue." They caution physicians to carefully assess cardiovascular risks before starting NSAID treatment.

http://click2.nejm.org/cts/click?q=137%3B67407589%3BeiE9g%2FGvnCS%2BA9hM6zkUHU4GkaJ%2Fj6Xi8I88p2FBIcA%3D

New diagnostic criteria for gestational diabetes mellitus
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was performed to determine internationally agreed upon diagnostic criteria forgestational diabetes. The International Association of Diabetes and Pregnancy Study Groups recommends the diagnosis be made when any of the following 3 75-g, 2-hour oral glucose tolerance test thresholds are met or exceeded: fasting 92 mg/dL, 1-hour 180 mg/dL, or 2 hours 153 mg/dL. American Journal of Obstetrics & Gynecology

http://www.ajog.org/article/S0002-9378(10)00419-9/fulltext

Weight gain after 50 seen as raising diabetes risk
A study in the Journal of the American Medical Association indicates that people who gain significant weight after age 50 are nearly three times as likely to develop Type 2 diabetes. Researchers reviewed data on about 4,200 people over the age of 65 and also found a relationship between increasing waist circumference and higher diabetes risk. 

http://consumer.healthday.com/printer.asp?AID=640414

Vitamin D insufficiency? Look to genetics.
Variants near genes involved in cholesterol synthesis, hydroxylation and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. (Free registration required.) The Lancet

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60588-0/abstract

Higher "good" cholesterol is associated with lower cancer risk
U.S. researchers said that for each 10-point increase in HDL, or "good," cholesterol, a patient's risk of cancer drops by 36% over about five years. However, researchers said the study, published in the Journal of the American College of Cardiology, does not prove cause and effect

http://consumer.healthday.com/Article.asp?AID=640003

Depression is tied to excess abdominal fat, study finds
A 20-year study of 5,100 individuals ages 18 to 30 showed that depressed people are more likely to gain excess fat around their waists. Elevated levels of the stress hormone cortisol, which is associated with depression and weight gain, might explain why people suffering from depression tend to add abdominal fat, according to one of the researchers. The study was published in the American Journal of Public Health.

Study links obesity to poor sexual health
A study in BMJ of more than 12,000 people in France showed that obese men and women have fewer sex partners compared with normal-weight counterparts. The study also showed that obese men have a higher risk of experiencing erectile dysfunction and contracting a sexually transmitted disease. Obese women were more likely to have an unplanned pregnancy and less likely to visit a gynecologist. HealthDay News

http://consumer.healthday.com/printer.asp?AID=640149

Study: Asthma risk more than triples in very obese people
A study published in Allergy of 4,500 men and women found that people who were the most obese were more than three times more likely to have asthma compared with normal-weight peers. The reason for the connection is not clear, researchers said.

http://www.reuters.com/article/idUSTRE64U31W20100601

Folic acid: No effect on cognitive function?
Randomized trials show no effect of folic acid, with or without other B vitamins, on cognitive function within three years of the start of treatment. Trials of longer duration, recording the incidence of dementia, as well as cognitive decline, are needed. The American Journal of Medicine

http://www.amjmed.com/article/S0002-9343(10)00131-2/fulltext

Gout drug can treat angina
Allopurinol seems to be a useful, inexpensive, well-tolerated and safe anti-ischaemic drug for patients with angina. The Lancet

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60391-1/abstract

Suppressing anger is bad for your heart
This study concluded that coronary artery disease patients who suppress their anger were at increased risk for adverse cardiac events, and this was accounted for by individual differences in Type D (tendency to experience distress and to be inhibited) personality. The American Journal of Cardiology

http://www.ajconline.org/article/S0002-9149(10)00101-3/fulltext

Depression patients prefer drugs to talk therapy, survey finds
U.S. patients with depression prefer antidepressants over talk therapy, and the drugs appear to be as effective, according to a Consumer Reports survey. Patients taking selective serotonin reuptake inhibitors, such as Zoloft and Prozac, reported greater satisfaction and fewer adverse effects compared with those who took serotonin-norepinephrine reuptake inhibitors. Reuters

http://www.reuters.com/article/idUSN0126519620100601

Cholesterol Reduction and the Brain–Heart Connection

A post hoc analysis of SPARCL data provides additional support for the benefits of statin therapy after a stroke or transient ischemic attack, in terms of both brain and cardiac protection.

Researchers previously reported a benefit from 80 mg of atorvastatin daily in preventing recurrent cerebrovascular and cardiovascular events over 5 years after a first stroke or transient ischemic attack (TIA) in the randomized, placebo-controlled, manufacturer-sponsored SPARCL trial (N Engl J Med 2006; 355:549; JW Cardiol Aug 30 2006). Now, the authors report subanalysis results. The 4731 participants had documented elevated LDL levels and stroke or TIA within the prior 6 months and no history or eviden ce of coronary heart disease (CHD). A handful of randomized patients were not included in the outcomes data for this report.

Rates of major coronary events (MCE) or any CHD endpoint were significantly lower with atorvastatin compared with placebo: Rates of MCE were 3.4% vs. 5.1%, respectively (absolute risk reduction, 1.7%; number needed to treat [NNT], 59). Rates of any CHD event were 5.2% and 8.6%, respectively (absolute risk reduction, 3.4%; NNT, 29). During the course of the study, stroke risk decreased with time but MCE risk remained stable. The rates of MCE and any CHD were similar between patients with and without carotid disease at baseline.

Statin Efficacy in Elders

Rosuvastatin lowered risk for major cardiovascular events.

Glynn RJ et al. Ann Intern Med 2010 Apr 20; 152:488

Zieman SJ and Ouyang P. Ann Intern Med 2010 Apr 20; 152:528

Metabolic Syndrome and Risk for Myocardial Infarction

Risk conferred by metabolic syndrome was similar to that conferred by diabetes alone.

Mente A et al. J Am Coll Cardiol 2010 May 25; 55:2390

Angiotensin-Receptor Blockers Linked to 'Modest' Increase in Cancer Risk

Angiotensin-receptor blockers (ARBs) are associated with a modestly increased risk for cancer, according to a meta-analysis published in the Lancet Oncology.

Researchers, examining data from five randomized trials comprising nearly 62,000 patients, found that those taking ARBs (85% were using telmisartan) had a significantly greater risk for new cancer than did controls (7.2% vs. 6.0%). When cancer type was analyzed, only lung cancer risk was significantly increased. The authors estimate that 143 patients would need to be treated for roughly 4 years for one excess cancer to occur.

The authors call the increase in cancer risk "modest" and the mechanism "uncertain." In addition, they note that conclusions could not be made regarding the exact risk with individual ARBs.

In an accompanying commentary, Dr. Steven Nissen says that until we have more data, clinicians "should use ARBs, particularly telmisartan, with greater caution." He recommends reserving the drugs for patients who cannot tolerate ACE inhibitors.

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970106-6/abstract

Angiotensin-Receptor Blockers and Cancer: An Inconvenient Truth?

A meta-analysis fuels uncertainty about safety, highlighting an imperative need for more data.

In 2003, the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity (CHARM) investigators reported a small but significant elevation in the rate of cancer deaths in patients treated with candesartan versus placebo. Now, U.S. investigators have conducted a meta-analysis of randomized controlled trials of angiotensin-receptor blockers (ARBs) to learn more about their effect on cancer.

Telmisartan was the ARB used in most of the studies. Of the five trials that included data on new cancer occurrence, the overall cancer rate was higher in the ARB groups than in the control groups (7.2% vs. 6.0%; relative risk, 1.08; 95% confidence interval, 1.01–1.15). When the analysis was restricted to the three trials in which cancer was a prespecified endpoint, the excess risk associated with ARBs persisted (RR, 1.11; 95% CI, 1.04–1.18). In the one study in which patients received concomitant angiotensin-converting enzyme (ACE)-inhibitor treatment, ARBs were associated with a 13% increase in risk for incident cancer (95% CI, 1.03–1.24). The number needed to harm was estimated to be 143 with 4 years of treatment.

FDA Announces Safety Review of Olmesartan

The FDA is reviewing the safety of the angiotensin-receptor blocker olmesartan (Benicar) after two ongoing trials among patients with type 2 diabetes suggested increased risk for cardiovascular death with the drug. For now, the agency emphasizes that it has not concluded that olmesartan increases the risk for death, and that the drug's benefits continue to outweigh its risks.

In one trial that prompted the safety review, the incidence of cardiovascular death was 0.67% with olmesartan and 0.14% with placebo. In the other trial, the incidence was 3.5% and 1.1%, respectively.

The FDA notes that other controlled trials evaluating olmesartan have not indicated heightened risk for cardiovascular death. The agency advises clinicians to continue prescribing the drug according to its label, and to report any adverse events to the MedWatch program.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm215222.htm

Hormone Replacement Therapy: Patch Less Risky for Stroke than Pill?

The risk for stroke associated with hormone replacement therapy (HRT) in postmenopausal women seems lower among those on low-dose transdermal regimens, according to a nested case-control study in BMJ.

From a cohort of almost 900,000 women over age 50, researchers age-matched 16,000 women who had a stroke over a follow-up period averaging 7 years with some 60,000 controls. Current users of oral estrogens, alone or in combination, had a higher stroke rate than nonusers of HRT.

When comparing oral and transdermal HRT directly, researchers found a lower stroke risk among transdermal users. However, high-dose patch users (>50 μg of estrogen) actually had a higher risk relative to nonusers (rate ratio, 1.88).

The authors warn that although their results suggest that the low-dose transdermal route may be safer, they "do not represent definitive evidence."

http://click.jwatch.org/cts/click?q=227%3B67405672%3BS0m3VyqMpx7058JCP3r3ZwS0OMjMXsoZQ0HBBWkfNgk%3D

MP3 Players Associated with Short-Term Hearing Loss

Listening to an MP3 player for just an hour can lead to temporary hearing loss, according to a small study in the Archives of Otolaryngology—Head & Neck Surgery.

Researchers in Belgium had 21 young adults with normal hearing listen to pop rock on an MP3 player at comfortable volumes for an hour, on six different occasions at least 2 days apart. The researchers found that, after listening, subjects experienced significant deterioration in hearing at high and low frequencies. Analyses revealed that hearing loss was temporary — participants recovered their normal hearing in between listening sessions.

The authors call for more research but say their findings "indicate the potential harmful effects" of listening to MP3 players.

http://archotol.ama-assn.org/cgi/content/short/136/6/538

Diabetes and Cancer Groups Issue Consensus Report

Experts from the American Diabetes Association and the American Cancer Society have published a consensus report on the association between diabetes and some types of cancer in CA: A Cancer Journal for Clinicians.

Their observations and recommendations include the following:

• Among the cancers associated with diabetes, the risk is highest for liver, pancreatic and endometrial cancers (roughly 2-fold or more) and lower for colorectal, breast, and bladder cancers (about 1.2- to 1.5-fold).
• Possible mechanisms to explain the association include hyperinsulinemia, hyperglycemia, and inflammation. Shared risk factors (e.g., obesity, aging, diet) may also play a role.
• Early studies indicate that metformin may be associated with a lower cancer risk while exogenous insulin may be associated with a higher risk. (More data are needed to determine whether insulin glargine poses greater risk than other insulins.)
• Cancer risk should not determine diabetes treatment in an average patient, but it may be a consideration in a higher-risk patient (e.g., one at risk for recurrence).

http://caonline.amcancersoc.org/cgi/content/full/caac.20078v1

Unintended Effects of Statin Drugs

Kidney failure and cataracts were associated significantly with statin use.

Statins lower risk for adverse cardiovascular events, especially in high-risk patients. In this large prospective U.K. cohort study, investigators sought to quantify unintended effects of these widely used drugs.

Of the more than 2 million study participants (age range, 30–84), about 225,000 were new statin users: 160,000 were prescribed simvastatin, 50,000 received atorvastatin, and 15,000 received pravastatin, rosuvastatin, or fluvastatin. Statin use was associated significantly with lower risk for esophageal cancer and higher risks for liver dysfunction (alanine transaminase levels 3x upper limit of normal), myopathy (clinical diagnosis or creatinine kinase level 4x upper limit of normal), acute kidney failure, and cataracts; liver dysfunction and acute kidney failure were dose-dependent. Adverse effects for individual statins were similar, except for liver dysfunction, in which risk was highest for fluvastatin. All excess risks persisted during treatment and returned to normal after drug cessation. Statin use was not associated with risk for osteoporotic fracture, venous thromboembolism, dementia, Parkinson disease, rheumatoid arthritis, or cancers (stomach, lung, breast, colon, kidney, and prostate cancers or melanoma).

http://www.ncbi.nlm.nih.gov/pubmed/20488911?dopt=Abstract

Hemoglobin A_1c Levels Are Higher in Black Than in White Adults

Black people consistently have higher hemoglobin A_1c (HbA_1c) concentrations than do white people, regardless of their underlying glycemia, according to a retrospective, cross-sectional study in the Annals of Internal Medicine.

Researchers examined data from two study populations that together comprised some 3500 non-Hispanic black or white adults without known diabetes who had both glucose and HbA_1c concentrations measured. In adjusted analyses, HbA_1c levels were significantly higher (by roughly 0.25 percentage points) among black than white subjects.

The higher HbA_1c concentrations among black participants were noted among subjects who were normoglycemic as well as those who were found to be prediabetic or diabetic (based on glucose measurements).

The authors conclude: "Until the mechanisms of racial differences in HbA_1c level are understood and can be applied to different persons, clinicians should not limit their assessment of glycemic control in their patients to measuring HbA_1c levels."

http://www.annals.org/content/152/12/770.abstract

Antibiotics for Inpatients with Chronic Obstructive Pulmonary Disease

A retrospective study shows several significant benefits.

Patients who are admitted for acute exacerbations of chronic obstructive pulmonary disease (COPD) often receive antibiotics, although roughly half of exacerbations are attributable to viral infections. Most randomized studies supporting antibiotic use are small and old.

Researchers used a U.S. healthcare quality database to conduct a retrospective cohort study of nearly 85,000 patients admitted for COPD exacerbations. About 10% required mechanical ventilation, died, or were readmitted for COPD within 30 days. Nearly 80% received at least 2 days of antibiotic therapy (most commonly with quinolones, cephalosporins, or macrolides). Treated patients were significantly less likely than untreated patients to receive mechanical ventilation (1.1% vs. 1.8%), die (1.0% vs. 1.6%), or to be readmitted for COPD (7.9% vs. 8.8%). However, treated patients also had a higher rate of readmission for Clostridium difficile infections than untreated patients (0.2% vs. 0.1%). In an analysis adjusted for a wide range of clinical and demographic factors, composite risk for treatment failure was 13% lower in the treated group.

http://www.ncbi.nlm.nih.gov/pubmed/20501925?dopt=Abstract