HHAL MEDICAL NEWS SEPTEMBER 2009
Two-Drug Combo Appears Better Than Monotherapy for Neuropathic Pain
A combination of the anticonvulsant gabapentin and the antidepressant
nortriptyline relieves neuropathic pain more effectively than either drug alone, Lancet reports.
In a crossover study,
56 adults with chronic pain due to diabetic polyneuropathy or postherpeticneuralgia were assigned
to the following treatment regimens: gabapentin alone, nortriptyline alone, and a combination of the two. All patients were
to receive each regimen, for 6 weeks each, but the sequence of the regimens was randomized. Drug doses were titrated to the
maximal tolerable dose.
Overall, mean daily pain intensity was significantly lower with combination therapy than
with monotherapy. Adverse events were similar with the three treatments, although significantly fewer patients reported dry
mouth with gabapentin than with the other regimens.
The authors discuss several study limitations but conclude: "We recommend combined
gabapentin and nortriptyline for patients who have a partial response to either drug alone and seek additional pain relief."
http://www.thelancet.com/journals/lanonc/article/PIIS0140-6736(09)61081-3/fulltext
H1N1 Update:
Bacterial Coinfection in H1N1-Related Deaths
Bacterial
pneumonia is contributing to deaths related to 2009 H1N1 influenza, according to a report released
online in MMWR. The CDC reiterates the importance of high-risk patients receiving the pneumococcal vaccine.
Researchers analyzed autopsy tissue specimens from 77 patients who died of H1N1-related
illness. Of those, 29% had evidence of bacterial coinfection. Streptococcus
pneumoniae was the most common bacteria found. (These cases
may not be an accurate representation of concurrentbacterial infections in H1N1 fatalities, according
to an editorial note, because this was not a systematic sample).
The CDC says the findings "underscore both the importance of pneumococcal vaccination
for persons at increased risk for pneumococcal pneumonia and the need for early recognition of bacterial pneumonia in persons
with influenza."
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58e0929a1.htm
Clues to CV risk in the young? Try waist-to-height ratio
The findings of this study underscore
the utility of waist-to-height ratio (people with waist-to-height ratio ≥0.5 with normal BMI between 18.5
to 24.9 has central obesity). in
detecting central obesity and related adverse cardiovascular risk among normal weight younger adults.
In conclusion, the results of the present study have underscored the utility of the waist-to-height ratio in detecting
asymptomatic normal weight younger adults with central obesity and related adverse cardiometabolic risk factors and their
burden on subclinical atherosclerosis. These observations have implications for preventive cardiology.
http://www.ajconline.org/article/S0002-9149(09)01005-4/fulltext
Hospitalization
for coronary heart disease down 31%
Hospitalizations dropped 31% for coronary heart
disease, 15% for heart attack and
14% for stroke from 1997 to 2007, according to a report by the Agency for Healthcare
Research and Quality. The data also
showed hospitalizations increased 28% for irregular heartbeat and 3% for congestive heart failure.
http://www.upi.com/Health_News/2009/09/21/Coronary-heart-disease-drops-31-percent/UPI-87381253577150/
Study: Obesity single biggest predictor for diabetes
The best single predictor of undiagnosed Type 2 diabetes is obesity, according
to results of the Diabscreen Study in the Netherlands, published in
the Annals of Family Medicine. Researchers said screening for Type 2 diabetes in primary care should target middle-aged and
older obese adults.
When the weight loss is from exercise
This study concluded that weight reduction by
aerobic exercise training in overweight and obese men increases central arterial distensibility.
This increase may contribute to the improvement in endothelial function, as assessed
by a decrease in plasma endothelin-1 and an increase in plasma nitric oxide, after exercise training-induced weight loss.
http://www.ajconline.org/article/S0002-9149(09)01055-8/fulltext
What's not to like about a low-calorie diet?
Is a very low
calorie diet a safe and effective weight-loss method? In a 12-week study of 132 Taiwanese participants, a diet of 400 to 800 calories per day resulted in 10% weight loss, as well as statistical improvements in blood
pressure, triglycerides and blood glucose. Non-alcoholic fatty liver disease also improved by 41.5%.
Conclusion
Both the VLCD-450 and 800 kcal/d can effectively and safely reduce body weight and improve NAFLD in 12 weeks in
obese Taiwanese participants. However, there is no additional benefit in prescribing the more restrictive diet intervention
in Taiwanese.
http://www.nutri tionjrnl.com/article/S0899-9007(09)00135-X/fulltext
What the elderly need to live independently
What can enable elderly to remain independently living and what
predicts permanent transition to a nursing home? Treatment for depression and incontinence
and programs to improve cognitive function and activities of daily living may extend time spent in an independent living
lifestyle.
Conclusion
Prevention and treatment
for depression, incontinence, and programs to improve or maintain cognitive function and ability to perform activities of
daily living among CCRC residents may prolong their independent living life.
http://www.jamda.com/article/S1525-8610(09)00112-1/abstract
Only 7.5% of Americans have all 5 heart-healthy factors
The U.S. obesity
epidemic is cutting into decades of steady progress against heart disease, researchers say. A study in Circulation found only
7.5% of Americans had all five major heart-healthy factors, compared with 10.5% in 1994.
http://healthday.com/Article.asp?AID=630974
Simple Test Might Detect 'Silent' Heart Disease
Even better, calcium scans don't lead to unnecessary tests,
researchers say
A simple test
that detects blockages in coronary arteries may help doctors identify patients with "silent" heart disease without
requiring major new medical expenses.
The findings were released in a study in the Sept. 29 issue
of the Journal of the American College of Cardiology.
The
tests -- coronary artery calcium scans -- pinpoint clogs in coronary arteries caused by plaque. While they can warn doctors
that certain patients are at risk of developing heart disease, insurance companies have been hesitant to cover them because
they could lead to expensive tests that might not turn up anything.
Still, "over
half of patients who suffer heart attacks have no warning that they have heart disease until the heart attack occurs. If we
knew the patients were at risk, current treatments could prevent the majority of these unnecessary events," according
to Dr. Daniel S. Berman, chief of cardiac imaging at the S. Mark Taper Foundation Imaging Center of Cedars-Sinai Heart Institute,
Los Angeles. "We had to address the concerns about unnecessary testing and costs related to this potentially lifesaving
procedure," he said in a news release from Cedars-Sinai.
In the new study, researchers
performed the scan on 1,361 volunteers who were at intermediate risk of heart disease (neither high nor low risk) and followed
them for four years.
High scores, indicating more plaque, were
linked to higher risk of heart problems. Those with low scores, however,
got fewer tests and the costs were lower, suggesting the tests won't lead to hugely expensive
tests in the general population of those who are screened.
Heart disease is the
top cause of death in the United States, killing an estimated 652,091 people each year, according to the U.S. Centers for Disease Control and Prevention.
The
Eisner Foundation, a private philanthropy in Los Angeles, financed the study. GE Healthcare, maker of one of the imaging machines used in the study, has provided
research support, grant support or consulting fees to several of the study authors.
http://healthday.com/Article.asp?AID=631599
Antioxidant supplements don't lower metabolic syndrome risk
A study of 5,220 middle-aged adults found those
taking antioxidant supplements didn't have a lower risk of developing metabolic syndrome over more than seven years compared
with a placebo group. However, researchers did find that people with the highest vitamin
C levels and beta-carotene levels at the study's start had a one-half and one-third lower risk of metabolic syndrome,
respectively, than people with the lowest levels. The study was published in the American Journal of Clinical Nutrition.
http://www.reuters.com/article/healthNews/idUSTRE5834LR20090904
Studies link smoke, carbon monoxide to heart disease
A study that included more than 1 million people
found even low levels of second-hand smoke increase a person's risk of dying from heart disease. A second study that included
more than 9 million people in 126 U.S. counties linked carbon monoxide air pollution to emergency department
visits for heart problems. Both studies were published in Circulation. Reuters
Treating
Resistant Hypertension: Cut Out the Salt
In a small randomized crossover study, a low-salt diet had dramatic effects on blood
pressure.
Pimenta E et al. Hypertension 2009 Sep 54:475
Chocolate
Is Associated with Lower Mortality Following First MI
Amount of chocolate consumption was related inversely to cardiac-related mortality during
an 8-year follow-up
Janszky I et al. J Intern Med 2009
Sep 266:248
Immobilization
and VTE: Are Long Trips Really Dangerous?
Travel for more than 8 hours did not significantly
increase the risk for venous thromboembolism.
Beam DM et al. Ann Emerg Med 2009 Aug 54:147
CT Screening for Lung Cancer: Early Results
Preliminary
outcomes from the DANTE trial show no differences between screening and control groups.
Infante M et al. Am J Respir Crit Care
Med 2009 Sep 1; 180:445
Quantifying
the Benefit of Anticoagulation for Atrial Fibrillation
Half of AF patients will benefit, half will
not — risk stratification is a vital component of decision making.
Singer DE et al. Ann Intern Med 2009 Sep 1; 151:297
Hart RG and Halperin
JL. Ann Intern
Med 2009 Sep 1; 151:355
Beneficial
Effect of Weight Loss on
Obstructive Sleep Apnea in
Patients with Diabetes
Participation in an intensive lifestyle intervention leading to weight loss is associated
with improvements in obstructive sleep apnea among patients with diabetes, reports Archives of Internal Medicine.
Researchers studied
some 260 overweight older patients (mean age, 61) with type 2 diabetes and obstructive sleep apnea (average apnea-hypopnea
index, 23 events per hour) for 1 year. Patients were randomized either to an intensive lifestyle intervention using restricted caloric intake and
moderate exercise, or to a series of three group sessions focusing on diet, exercise, and social support.
By year's end,
intensive-intervention patients had lost significantly more weight and showed a significant improvement in sleep apnea, compared
with controls. In the control group, patients showed a worsening in their sleep apnea, despite maintaining stable weight.
The greatest improvements in the apnea-hypopnea index were among patients with the highest initial values and the greatest
weight loss.
Conclusions Physicians and their patients can expect that weight
loss will result in significant and clinically relevant improvements
in OSA among obese patients with type 2 diabetes.
http://archinte.ama-assn.org/cgi/content/abstract/169/17/1619
Another Diabetes Drug Linked to Acute Pancreatitis
The prescribing
information for the type 2 diabetes drug sitagliptin (marketed alone as Januvia, and combined with metformin as Janumet) must be revised to note the incidence of acute pancreatitis
in some patients using the drug, the FDA announced
on Friday.
Some 88 cases have been reported since sitagliptin was approved in 2006; two cases were necrotizing
or hemorrhagic pancreatitis. Overall, 20% occurred within a month of drug initiation, and about half resolved
after drug discontinuation.
The FDA advises healthcare providers to monitor patients on sitagliptin for signs of
pancreatitis (e.g., abdominal pain, nausea, vomiting), and to discontinue the drug if pancreatitis is suspected.
Patients should also be educated about these symptoms.
It is not known whether sitagliptin users with histories of pancreatitis are at increased
risk for the condition, the FDA says.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm183800.htm
Surgery Modestly Better Than Nonsurgical
Treatments for Carpal Tunnel Syndrome
In patients with mild-to-moderate
carpal tunnel syndrome who've tried splinting without success, surgery produces greater functional and symptomatic improvements
than nonsurgical treatment, aLancet study shows.
Among more than 100 patients randomized to surgery or nonsurgical therapy (including
splinting and hand exercises), substantial crossover occurred. Intent-to-treat analyses showed 67% of patients had functional
improvement of 30% or more at 1 year with surgery, compared to 46% with nonsurgical treatment. In as-treated analyses, improvements
were 73% and 33%, respectively. Surgery was not associated with any "clinically important" adverse events.
The authors write
that differences between the groups, while statistically significant, were "of moderate clinical relevance."
Commentators conclude
that although nonsurgical treatments have their place, especially for those with short histories of carpal tunnel, "patients
... who do not have satisfactory improvement with non-surgical treatment should be offered surgery."
Interpretation
Symptoms
in both groups improved, but surgical treatment led to better outcome than did non-surgical treatment. However, the clinical
relevance of this difference was modest. Overall, our study confirms that surgery is useful for patients with carpal tunnel
syndrome without denervation.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61517-8/abstract
Bigger Waist Means Higher Asthma Risk
Women with waist measurements >88 cm had higher risk for asthma than women in the same BMI categories but with smaller waist measurements.
Obesity is a risk factor for adult-onset
asthma, but the contribution of excess abdominal fat to this relation is unclear. Investigators for the California
Teachers Study administered questionnaires to a cohort of 133,480 female school teachers and administrators. Information was
obtained about current asthma-related symptoms as well as height and weight at age 18 and at study entry. Participants measured
and self-reported their waist circumference.
Of 88,300 eligible participants, 13% were obese (BMI >30.0 kg/m2).
Prevalence of asthma was 7.6% overall, 11% in obese class I women (BMI, 30.0–34.9), 13% in obese class II women (BMI,
35.0–39.9), and 18% in extremely obese women (BMI >40.0). Overweight women (BMI, 25.0–29.9) had 40% higher risk for asthma than normal-weight
women (BMI, 18.0–24.9), whereas extremely obese women had more than threefold higher risk (odds ratio, 3.3). Analysis adjusted for smoking status, age, race, and ethnicity showed
that women who reported waist measurements >88.0 cm (35.2
inches) compared with those who had
waist circumferences 88.0 cm had higher risk for
asthma regardless of whether they were normal weight (OR, 1.4), overweight (OR, 1.7), or obese (OR, 2.4).
Comment: These authors did not control for potential confounders such as other comorbid conditions,
family histories of asthma, or environmental exposure to allergens. Nonetheless, their findings show that excess weight alone
is not a key determinant of asthma risk; where fat is deposited is also crucial. Visceral fat differs metabolically from other body fat stores
in its association with inflammatory and prothrombotic states (e.g.,insulin
resistance, cardiovascular disease). Thus, although higher BMI generally was associated with excess risk for asthma — an inflammatory condition
of the airways — women who had large waist measurements were at even greater risk. With 66% of the U.S.
population now overweight or obese, these results suggest a reason for the rising prevalence of asthma: the expanding American
waistline.
Maternal Use of Sertaline, Citalopram Linked to Septal Heart Defects in Offspring
Women who use the antidepressants sertraline (Zoloft) or citalopram (Celexa) early in pregnancy face
increased risk for septal heart defects in their offspring, BMJ reports
online.
Researchers examined data on more than 490,000 infants born in Denmark
between 1996 and 2003. They found that women who filled prescriptions for sertraline and citalopram (but not otherSSRIs) during their first trimester were significantly more likely to have children with septal heart defects (but not other malformations)
than those who didn't use SSRIs (odds ratios: 3.2 and 2.5, respectively).
The authors and an editorialist (both
with ties to SSRI manufacturers) note that the absolute risks for septal heart defects were low: 0.9% in children exposed
to at least one SSRI and 2.1% in those exposed to more than one. The editorialist concludes: "Clinicians and patients
need to balance the small risks associated with SSRIs against those associated with undertreatment or no treatment."
http://www.bmj.com/cgi/content/full/339/sep23_1/b3569
Prostate-Specific Antigen Doesn't Measure Up as a Screening Test
Despite its value as a prognostic marker, prostate-specific antigen does not meet criteria for use as a screening
test for prostate cancer, according to a BMJ study published online.
Using a large Swedish cohort linked to a national cancer registry, researchers
compared the initial PSA values of those who developed prostate cancer over roughly 7 years post-screening with other matched
men who did not develop cancer. The overlap in PSA values between the two groups frustrated researchers' efforts to find
a cut-off value that had a high specificity as well as a sensitivity above 50%. (However,
they note that a PSA value below 1 ng/mL "virtually ruled out" a diagnosis during the follow-up period.)
An accompanying review
argues that "data on [PSA testing's] costs and benefits remain insufficient to support population based screening."
Conclusions No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a
screening test. Prostate specific antigen concentrations below 1.0
ng/ml virtually ruled out a prostate cancer diagnosis during the
follow-up. Additional biomarkers for early detection of prostate
cancer are needed before population based screeningfor prostate cancer should be introduced.
http://www.bmj.com/cgi/content/full/339/sep24_1/b3537
Angiotensin-Receptor Blockers for Microalbuminuria
ARBs didn't prevent
adverse renal outcomes in patients with cardiovascular disease or diabetes.
The effect of angiotensin-receptor blockers (ARBs) on renal outcomes among patients at high vascular risk but without
overt diabetic nephropathy and
among normoalbuminuric patients with diabetes is unknown. In two reports, researchers examined the effects of ARBs in these
groups.
In a 5-year industry-sponsored international randomized trial, investigators compared telmisartan (Micardis)
with placebo in 5927 adults (mean age, 67) who could not tolerate angiotensin-converting–enzyme inhibitors. All participants
had cardiovascular disease or
diabetes and end-organ damage but no macroalbuminuria or heart failure. No significant difference was seen in the combined
outcome of serum creatinine doubling or requisite dialysis; in fact, doubling of creatinine levels and decreases from baseline in glomerular filtration rate were significantly more common with telmisartan
than with placebo.
In another report, investigators presented results of three 5-year international industry-sponsored
randomized trials of candesartan (Atacand): Two trials involved 3326 patients (age, <55) with type 1 diabetes (1 trial
each for patients with and without retinopathy) and one trial involved 1905 patients (age, <75) with type 2 diabetes. Subjects
were normotensive (people with type 2 diabetes could have controlled hypertension) and normoalbuminuric.
Candesartan did not lower risk for developing microalbuminuria in any of the trials.
CONCLUSION: In adults with vascular disease but without macroalbuminuria, the effects of telmisartan on major renal
outcomes were similar to those of placebo.
http://www.ncbi.nlm.nih.gov/pubmed/19451556?dopt=Abstract
Comorbid Diabetes and Depression:
Increased Mortality Beyond Cardiovascular Causes
Among patients with diabetes, those with comorbid depression appear to be at greater
risk for death from noncardiovascular causes compared to those without depression, according to anAnnals of Family Medicine study.
Nearly 4200 U.S.
adults with diabetes completed health and depression questionnaires and then were followed for roughly 4.5 years. During that
time, 14% died.
After adjustment for demographics, clinical characteristics, and health habits, patients with major
depression at baseline (about 12% of all patients) were about twice as likely to die from noncardiovascular, noncancer causes
(e.g., infection, renal failure) as those without depression. Depressed patients also had a 50% higher risk
for all-cause mortality. (Suicide accounted for only 4 deaths.)
The authors say their results "suggest
that patients with comorbid diabetes and depression face increased mortality risks beyond cardiovascular-related mortality."
They note that underlying mechanisms likely include both physiologic and behavioral pathways.
Annals
of Family Medicine article (Free
PDF)
http://www.annfammed.org/cgi/reprint/7/5/414
Physical Activity, Function, and Longevity Among the Very Old
Jochanan Stessman, MD; Robert Hammerman-Rozenberg, MD; Aaron Cohen, MD; Eliana Ein-Mor, MA; Jeremy
M. Jacobs, MBBS
Arch Intern Med. 2009;169(16):1476-1483.
Background Recommendations
encouraging physical activity (PA) set no upper age limit, yet evidence supporting the benefits of
PA among the very old is sparse. We examined the effects of continuing, increasing, or decreasing PA levels
on survival, function, and health status among the very old.
Methods Mortality data
from ages 70 to 88 years and health, comorbidity, and functional status at ages 70, 78, and 85 years were
assessed through the Jerusalem Longitudinal Cohort Study (1990-2008). A representative sample of 1861 people
born in 1920 and 1921 enrolled in this prospective study, resulting in 17 109 person-years
of follow-up for all-cause mortality.
Results Among physically active vs sedentary participants, respectively,
at age 70, the 8-year mortality was 15.2% vs 27.2% (P < .001); at age 78, the 8-year
mortality was 26.1% vs 40.8% (P <.001); and at age 85 years, the 3-year mortality
was 6.8% vs 24.4% (P < .001). In Cox proportional-hazards models adjusting for mortality
risk factors, lower mortality was associated with PA level at ages 70 (hazard ratio, 0.61;
95% confidence interval, 0.38-0.96), 78 (0.69; 0.48-0.98), and 85 (0.42; 0.25-0.68). A significant survival benefit
was associated with initiating PA between ages 70 and 78 years (P = .04) and ages 78 and
85 years (P < .001). Participation in higher levels of PA, compared with being sedentary, did
not show a dose-dependent association with mortality. The PA level at age 78 was associated with remaining
independent while performing activities of daily living at age 85 (odds ratio, 1.92; 95% confidence
interval, 1.11-3.33).
Conclusions Among the very old, not only
continuing but also initiating PA was
associated with better
survival and function. This finding supports the encouragement of PA into advanced old age.
Inhaled Steroids
in COPD: Is Risk for Pneumonia Really Higher?
Risk was not elevated in patients who received
budesonide.
Do inhaled corticosteroids
elevate risk for pneumonia in patients with chronic obstructive pulmonary disease? Several clinical trials, observational studies, and meta-analyses suggest that they do, by as much as 70%. But, in other trials,
researchers have reported lower risk, and previous meta-analyses have been criticized for methodological weaknesses, such
as combining trials of inhaled budesonide with those of fluticasone.
Canadian researchers
pooled patient-level data from seven large clinical trials in which more than 7000 patients with COPD were
randomized to inhaled budesonide or placebo, with or without the long-acting β2-agonist formoterol, for 6
to 12 months. In both groups, 3% of patients developed pneumonia; in 1% of budesonide recipients and in 2% of placebo recipients,
it was a serious adverse event (i.e.,
causing hospitalization or death), with no significant difference between groups, before or after adjustment for potential
confounders.
Comment: Budesonide is
cleared more rapidly from the airways than fluticasone, and the authors speculate that this fact could help explain why pneumonia
risk is not elevated with budesonide (as it seems to be with fluticasone). Surprisingly, despite high mortality associated
with community-acquired pneumonia, no study has shown that fatal pneumonia is more common among patients who receive inhaled
steroids, which suggests that pneumonias induced by inhaled steroids are relatively mild. An editorialist concludes that the
benefits of inhaled steroids in COPD patients continue to outweigh the risks substantially
INTERPRETATION:
Budesonide treatment for 12 months does not increase the risk of pneumonia in patients
with COPD during that time and therefore is safe for clinical use in such patients.
http://www.ncbi.nlm.nih.gov/pubmed/19716963?dopt=Abstract
Maternal Smoking During Pregnancy Linked
to Psychotic Symptoms in Children Years Later
Children whose mothers
smoked during pregnancy are at increased risk for psychotic symptoms by age 12, according to a longitudinal study in the British Journal of Psychiatry.
Researchers gathered information on women's use of tobacco, alcohol, and cannabis
during pregnancy and then evaluated their offspring for psychotic symptoms 12 years later. Of nearly 6400 children assessed,
about 12% had suspected or definite psychotic symptoms.
In adjusted analyses, maternal smoking was associated with increased risk for psychotic
symptoms in offspring, with a dose-response effect (odds ratio for trend, 1.2). A link between alcohol use and
psychotic symptoms was limited to mothers who consumed more than 21 units a week. Cannabis use was not associated with symptoms.
The authors say their
findings are "consistent with accumulating evidence from animal models of adverse effects on brain development from in utero nicotine exposure."
Conclusions
These
findings indicate that risk factors for development of non-clinical psychotic experiences may operate during early development. Future studies of how in
utero exposure to tobacco affects cerebral development and function may lead
to increased understanding
of the pathogenesis of psychotic phenomena.
http://bjp.rcpsych.org/cgi/content/full/195/4/294
Systemic Inflammatory Events Linked to Faster Cognitive Decline in Alzheimer Disease
Patients may ask about a Neurology study suggesting that respiratory infections and other inflammatory events may hasten cognitive
decline in Alzheimer disease (AD).
Some 300 adults with
AD underwent cognitive testing and
then provided blood samples for measurement of the proinflammatory cytokine tumor necrosis factor (TNF)-α. In addition, caregivers were asked whether patients had recently experienced systemic inflammatory
events (e.g., respiratory or gastrointestinal infections). Both patients and caregivers were assessed at baseline and
periodically throughout 6 months.
High baseline levels of TNF-α were associated
with cognitive decline during follow-up. In addition, patients with at least one systemic inflammatory
event during the study (about 50% of patients) had an increase in TNF-α levels — and twice the rate of cognitive
decline.
The authors conclude that "dampening down systemic TNF-α may prove to be beneficial in AD."
http://www.neurology.org/current.shtml
Pioglitazone vs. Rosiglitazone in Older Patients with Type 2 Diabetes
Pioglitazone was associated with lower risk for death and heart failure.
Two thiazolidinediones
are available in the U.S.: pioglitazone (Actos) and rosiglitazone (Avandia). However, researchers have raised concerns about the cardiovascular
safety of these drugs. In this retrospective cohort study, Canadian investigators assessed risk for myocardial infarction, heart failure, and death in nearly 40,000 older patients (age, 66) with type 2 diabetes who received pioglitazone or
rosiglitazone during a 6-year period.
Overall, the composite endpoint of death, MI, and heart failure occurred in 5.3% of
patients who took pioglitazone and in 6.9% of patients who took rosiglitazone; a significantly lower risk with pioglitazone
persisted after adjustments for many potential confounders and drug doses (hazard
ratio, 0.83). Likewise, pioglitazone recipients had significantly lower risk
for death (HR, 0.86) and heart failure (HR, 0.77) — but not MI — than did rosiglitazone recipients.
Comment: Among older patients with type 2 diabetes, pioglitazone is associated with lower
risk for death and heart failure than is rosiglitazone. The authors propose several possible reasons for these differences:
Pioglitazone has more favorable effects on lipids, has anti-inflammatory effects, and is less potent than
rosiglitazone in promoting salt and water retention. According to a 2009 consensus statement from American and European diabetes
groups, thiazolidinediones should not be used as first-line agents in patients with type 2 diabetes (because they raise risk for
heart failure and fractures), and rosiglitazone should not be used at all.
