April 6th, 2015
Weight-Loss Programs: Slim Evidence and Thin Results
Larry Husten, PHD
A new study concludes that some weight-loss programs may be slightly better than other programs but that in the long run none of the programs have been able to show a substantial weight loss over a sustained period. For even the best programs, an editorialist writes, “weight loss is modest and likely below patients’ expectations.”
In a paper published in Annals of Internal Medicine, researchers report on an updated systematic review of studies evaluating weight-loss programs. They looked for U.S. trials involving 31 different programs but were able to find only 45 studies that qualified (and only 39 of these were randomized, controlled trials) involving only 11 of the weight-loss programs. (The 11 programs were Weight Watchers, Jenny Craig, Nutrisystem, Health Management Resources, Medifast, OPTIFAST, Atkins, The Biggest Loser Club, eDiets, Lose It!, and SlimFast.)
The trials that were performed were plagued by numerous shortcomings, including limited duration and followup, high rates of dropouts in people participating in the trials, poor adherence to the diet programs, and a high risk of bias.
As the one-eyed man is king in the land of the blind, only two weight-loss programs, Jenny Craig and Weight Watchers, were able to show even a modest weight loss at one year. Compared to controls, who generally received traditional counseling and education, weight loss was only 2.6% greater for Weight Watchers and 4.9% greater for Jenny Craig. At three months Nutrisystem led to a 3.8% greater weight loss. Very low-calorie programs like Health Management Resources, Medifast, and OPTIFAST resulted in a 4.0% greater short-term weight loss but these losses were attenuated over time. The evidence to evaluate most self-directed programs was weak. Low-carb programs like Atkins had promise but the trials were limited by design problems and bias.
In an accompanying editorial, Christina Wee writes that the study “highlights something that researchers in the behavioral weight-management field have known for decades: Structure and intensity of contact are highly correlated with program success. It is unsurprising that highly structured programs with in-person social support, such as Weight Watchers and Jenny Craig, seem more effective in the long term than less structured interventions.”
The study authors concluded with a very modest endorsement of Weight Watchers and Jenny Craig, stating that “clinicians might consider prioritizing referral only for those commercial programs that have a substantial body of evidence showing a consistent, long-term effect.”
But, writes Wee, the weight loss with such programs, including Weight Watchers and Jenny Craig, “is modest and likely below patients’ expectations.” She concludes: “Whether patients value the modest weight loss produced by these programs enough to absorb the financial cost and sustain behavioral change is also unclear.”
April 6th, 2015
Cardiac Arrest During Exercise in Middle-Aged People
Larry Husten, PHD
Dropping dead while exercising is a common fear, especially among middle-aged men. Unfortunately there have been limited data on the precise rate of sudden cardiac arrest (SCA) in middle-aged people and little understanding about the medical history of the victims of SCA. Now a new study fills in some important gaps in knowledge and shows that this fear is largely misplaced, given the small risk that exercise will lead to sudden cardiac death in most middle-aged people.
In a paper published in Circulation, researchers scrutinized all SCA cases in people 35-65 years old in the Portland, Oregon area over a ten year period — the first such analysis performed in the United States, say the authors. Over the study period there were only 67 cases of sport-related SCA in the study population, representing only 5% of the total 1,247 SCA events in middle-aged people. This is “a fact that is likely to encourage sports activities among middle-aged athletes,” the authors wrote.
A second important finding is that nearly two-thirds of the people who had SCA had previous cardiovascular symptoms or had been diagnosed with cardiovascular disease. This finding “suggests that utilization of educational and general awareness approaches may further decrease sports-associated SCA burden.”
Middle-aged men were 18 times more likely to have a sport-associated SCA than women. The authors estimated that in the overall middle-aged U.S. population 2,269 men would have an event each year, compared with only 136 women. They speculated that this difference may be due to “inherent sex differences” or differences in the rate of participation or the vigor and duration of exercise.
The authors emphasized that the small increase in short-term risk associated with exercise is almost certainly outweighed by “the long-term benefits of regular exercise on cardiovascular health.” They said “the findings from this study should in no way discourage patients with cardiovascular risk factors from engaging in regular, appropriate physical exercise within a framework of simple guiding rules from the treating physician.”
April 6th, 2015
Bringing Clarity and Consensus to the Treatment of Hypertension in Patients with CAD
Elliott Antman, MD
CardioExchange invited Elliot Antman, President of the American Heart Association (AHA), to discuss the recently released scientific statement from the AHA, the American College of Cardiology (ACC), and the American Society of Hypertension (ASH) on the treatment of hypertension in patients with existing coronary artery disease (CAD). Our news coverage of the statement can be found
It is important to understand the context in which this most recent statement from the AHA/ACC/ASH was generated and the gaps it is intended to fill. The present statement is an update of a 2007 AHA statement that also focused on the management of hypertension in patients with ischemic heart disease. Thus, it focuses predominantly on the secondary prevention of events in patients with stable angina, an acute coronary syndrome, and/or heart failure of ischemic origin.
While some of these topics were on the initial list of 23 questions put forward by the group originally empaneled as JNC 8, their report was restricted to only three questions and the major focus was on primary prevention in the general community. This fact, coupled with their controversial recommendation calling for a relaxation of the blood pressure (BP) target to 150/90 mm/Hg in those over the age of 60 in the general population without chronic kidney disease or diabetes has created confusion in the clinical community.
Thus, the present document emphasizes:
1. Hypertension is an important risk for fatal CAD over a wide range, beginning at 115/75 mm/Hg for patients of all ages, and each increase in systolic BP of 20 mm/Hg doubles the risk of a fatal coronary event.
2. The target of < 140/90 mm/Hg is reasonable for secondary prevention of cardiovascular events in patients with hypertension and CAD, and an even lower target of < 130/80 mm/Hg, which is supported by epidemiologic data, may be appropriate in some individuals.
3. As opposed to the general population, where beta-blockers are less effective in preventing myocardial infarction or stroke than other classes of antihypertensive drugs, beta-blockers should be included in the treatment of hypertension in patients with CAD because of their additional cardioprotective effects.
The AHA remains concerned about the prevalence of hypertension in this country (affecting about 80 million adults) and its human and economic cost to our society. The secondary prevention targets in the present document provide useful guidance for the practitioner while we continue to work on our more comprehensive clinical practice guideline on hypertension.
It is important to remember that hypertension exerts its harmful effects over a time horizon that is measured in decades and most randomized, controlled trials (RCTs) do not have a long enough follow up to sample the time horizon adequately (see JAMA 311: 1195, 2014). Therefore, the upcoming comprehensive guideline will include a review of evidence both from RCTs and nonRCT sources to provide a full picture of the information that should be considered when treating a patient with hypertension. In the meanwhile, the AHA recommends a BP target of < 140/90 mm/Hg — this is especially important to reduce the risk of stroke, an important endpoint that will be a focus of the upcoming guideline.
April 2nd, 2015
Liberal Changes to rt-PA Contraindications for Acute Ischemic Stroke
Craig Cocchio, PharmD, BCPS
This post was originally published on Craig Cocchio‘s blog, Emergency Medicine PharmD.
Flying in under the radar recently were the changes to the Alteplase (rt-PA) prescribing information. These changes pertain to the contraindications to use of the drug in acute ischemic stroke. It’s hard to find anything—and puzzlingly so—on the particulars about why the FDA authorized such changes.
The updated contraindications now read as follows: Link
Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit:
- Current intracranial hemorrhage
- Subarachnoid hemorrhage
- Active internal bleeding
- Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
- Presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms)
- Bleeding diathesis
- Current severe uncontrolled hypertension
Without the old contraindications to compare to side by side, the changes may not be obvious. From a 2013 package insert, the contraindications read as follows (changes italicized):
Activase therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which could result in significant disability or death:
- Evidence of intracranial hemorrhage on pretreatment evaluation
- Suspicion of subarachnoid hemorrhage on pretreatment evaluation
- Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke
- History of intracranial hemorrhage
- Uncontrolled hypertension at time of treatment (e.g., > 185 mm Hg systolic or > 110 mm Hg diastolic)
- Seizure at the onset of stroke
- Active internal bleeding
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Known bleeding diathesis including but not limited to:
- Current use of oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) > 1.7 or a prothrombin time (PT) > 15 seconds
- Administration of heparin within 48 hours preceding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation.
- Platelet count < 100,000/mm3
The changes can be significant, particularly the language introducing the contraindications. The consequences which were previously “significant disability or death” are now simply “situations in which the risk of bleeding is greater than the potential benefit.” If you didn’t catch the specific changes, rt-PA is no longer contraindicated in patients with:
- History of intracranial hemorrhage
- Seizure at the onset of stroke
Furthermore, the language describing specific bleeding diatheses (drugs: warfarin, diabigatran, rivaroxaban, etc.; thrombocytopenia or prolonged bleeding times) and describing what constitutes “uncontrolled hypertension” are now very vague.
At this point the guidelines have not updated their list of contraindications… for now.
April 2nd, 2015
Global Cardiovascular Deaths Continue to Rise Despite Gains in Prevention and Treatment
Larry Husten, PHD
Improvements in the treatment and prevention of cardiovascular disease haven’t been able to prevent a worldwide rise in cardiovascular deaths in a growing and aging population, according to the authors of a paper published in the New England Journal of Medicine. Using mortality data from the Global Burden of Disease Study 2013, the authors set out to “disentangle” the effects on cardiovascular mortality of population growth, an aging population, and epidemiological changes (defined as changes in risk factors and the effect of efforts to prevent and treat CV disease).
From 1990 to 2013 the total number of deaths caused by cardiovascular disease increased by 40%, from more than 12 million to more than 17 million a year. This growth was fueled by a 55% increase in the number of deaths caused by the aging population and a 25% increase in the number of deaths due to population growth. These increases occurred despite a 39% reduction in cardiovascular deaths explained by epidemiological changes over the same period.
There were broad variations in the pattern based on the region and income of countries. The absolute number of deaths from CV disease declined in Central Europe and Western Europe but increased everywhere else. The biggest absolute increase occurred in South Asia, where the number of CV deaths almost doubled, reaching 1.7 million in 2013. The number of deaths remained fairly constant in Southern Latin America, Australasia, and high-income North America because, the authors said, “population aging and growth balanced out declines in age-specific death rates.”
Particularly in high-income countries, the “dramatic reductions” in CV deaths not related to the growth or aging of the population “are probably due to the combined effect of birth cohorts’ decreased exposure to tobacco smoking, improvements in diet, and improved treatment of cardiovascular disease and cardiometabolic risk factors targeting the prevention of cardiovascular disease, and improved treatment of cardiovascular disease.”
March 31st, 2015
New Consensus for Managing Hypertension in Patients with Coronary Artery Disease
Larry Husten, PHD
There’s been a lot of drama in the hypertension field over the past few years. Initially sparked by the decision of the National Institutes of Health to halt its sponsorship of national guidelines, the subsequent appearance of multiple guidelines with divergent recommendations led to even more controversy and discussion. Now, however, the appearance of a new scientific statement may indicate that some of the drama is dissipating, at least in one important subset of the field.
The scientific statement from the American Heart Association, the American College of Cardiology, and the American Society of Hypertension covers the important area of the treatment of hypertension in patients with existing coronary artery disease. A key element of the statement is that it is in accord with the Eighth Joint National Committee (JNC 8) guideline and reinforces the blood pressure goal of less than 140/90 mm Hg in this group of patients. “This is important since confusion has arisen in the clinical community over the last year regarding the appropriate target for blood pressure management in the general population,” said Elliott Antman, President of the American Heart Association, in a press statement.
For some patients who have had a previous cardiovascular event, though, a lower target of less than 130/80 mm Hg may be considered appropriate. The statement cautions, however, against lowering blood pressure too rapidly and against lowering diastolic blood pressure lower than 60 mm Hg, particularly in patients over the age of 60.
Beta-blockers are a cornerstone of antihypertensive treatment in this population, though many patients may also require additional drugs. The statement also summarizes important information about the modification of additional cardiovascular risk factors, including weight loss, cholesterol control, smoking cessation, and treatments for diabetes.
Christopher O’Connor, a co-author of the statement, said in an email that the publication represents “a major effort to bring clarity and consensus for hypertension management in cardiac and vascular patients.”
March 30th, 2015
Selections from Richard Lehman’s Literature Review: March 30th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
NEJM 26 Mar 2015 Vol 372
Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease (pg. 1204): Cabbage comes in and out of favour. I personally prefer the old fashioned kinds, such as Savoy or Sweetheart, cut in strips and stir-fried in nut oil with a few chopped walnuts, perhaps some shallot and bacon. Sprinkle with balsamic vinegar. I can’t get on with Cavolo Nero which has the texture and taste of a plastic bag, however you cook it. CABG started falling out of favour with the arrival of bare metal stents and even more with the allegedly superior drug-eluting stents. Here’s the first of the two trials in this issue. It was publicly funded in Korea and is open access. Recruitment was slow and the trial was terminated at two years. At that point, the composite end-point (grr) of death, myocardial infarction, or target-vessel revascularization had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], −0.8 to 6.9; P=0.32 for noninferiority): not significant. Two years on, and the difference in favour of CABG had become just significant (CI 1.01 to 2.13; P=0.04).
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Disease (pg. 1213): On to the next study, this time run by a stent manufacturer (Abbott Vascular) and behind a paywall. It’s a clinical registry study of 9223 patients with similar propensity scores who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG. At nearly three years on average, the risk of death was the same. The risk of stroke was higher in the CABG group, while the risk of myocardial infarction or repeat revascularization was a bit higher in the stent group. This is the kind of study which cries out for replication by reanalysing the same individual patient dataset. Even then, propensity scoring is no substitute for true randomization. As the editorial says, these two studies take us no further forward in being able to put informed choices before patients.
BMJ 28 Mar 2015 Vol 350
Short term exposure to air pollution and stroke: Somewhat better evidence links short term exposure to air pollution with acute stroke. There is a massive literature: out of 2748 articles, 103 satisfied the inclusion criteria for this meta-analysis, and its conclusions are based on a total of 6.2 million events across 28 countries. The bad gases are carbon monoxide, sulfur dioxide, and nitrogen dioxide, and particulate matter also looks like a culprit for bringing on stroke, both at <2.5 µm or <10 µm diameter. My lord, should you wish to be spared a stroke, you must avoid port wine, eat vegetables, and take exercise henceforth in your country estates. My fee will be 100 guineas.
March 30th, 2015
How Do You Like Them Apples?
Larry Husten, PHD
An apple a day does not appear to keep the doctor away but, a new study semi-seriously suggests, it may keep the pharmacist away.
Although apples have long been considered a healthy snack, whether eating apples actually reduces healthcare use has not been assessed until now. In a paper published in JAMA Internal Medicine researchers examined the association between healthcare utilization and apple consumption in more than 8,000 adults participating in the National Health and Nutrition Examination Survey.
At first glance apples appeared to be related to significant benefits. Apple eaters, defined as those who ate at least one small apple each day, were more likely to “keep the doctor away” (defined as no more than one doctor visit in the past year): 39% versus 33.9% for non-apple eaters. Apple eaters were also less likely to take prescription drugs: 47.7% vs. 41.8%. But the researchers found no difference between the groups in overnight hospital stays or in visits to a mental-health professional.
The results were less robust after the researchers adjusted for sociodemographic and health-related factors. Disproving the adage about an apple a day, the primary endpoint — the reduction in the number of doctor visits — was no longer statistically significant. However, the finding that apple eaters avoided taking prescription drugs remained marginally significant.
Apple eaters constituted only 9% of the group studied, which in the U.S. works out to 19.3 million adults who are apple eaters and 207.2 million adults who are not. The authors calculated, though it is unclear whether they were entirely serious, that universal apple consumption among U.S. adults would result in a $47 billion reduction in prescriptions at a cost of $28 billion in apples.
The authors acknowledged the major limitation of their study: “Apple eaters were, in fact, measurably different from non-apple eaters and would be expected to differ in other, unmeasured ways. Specifically, individuals who eat apples may be more health conscious and otherwise healthier, which could entirely explain the associations we observed.”
In an editorial note, JAMA Internal Medicine editor Rita Redberg informs readers that the article is part of the journal’s “first April Fool’s issue.” In an email, Redberg said that she “did not ask the readers to discount the findings.” Instead, she said, the paper shows that “a study could be scientifically rigorous and still have some humor or light side, as this one did.”
March 27th, 2015
Fighting the Contradiction: A Hospital Rolls Out the Red Carpet for Smokers
Jean-Pierre Usdin, MD
Reading a recent special article and editorial in the New England Journal of Medicine about diseases caused by smoking has reignited my resentment toward the red carpet that is rolled out for smokers in the hospital where I practice.
Following the courageous decisions made by many American mayors to ban smoking in public places, including parks, I had hoped that the management of the American Hospital of Paris would impose a smoking ban throughout its premises, including the garden.
A Special Place Just for Smokers
If you were to come visit our hospital, you’d find that, under the “Tobacco-Free Hospital” signs, there is now an arrow pointing to the “Smoking Shelter”. Unfortunately, this is not a joke!
Under alleged pressure from smokers, and despite protestations from many professionals, a glass room (much like a lovely greenhouse) has just been completed.
Is this irony or provocation? The entrance to this smoking room is adjacent to the Health Center, which is dedicated to screening for many diseases, including cardiovascular disease. The hospital is very proud of the Health Center, however, when patients walk out the doors they will now be confronted with smokers from this room dedicated entirely to smoking.
What’s more, it is a very elegant room: designer pedestal tables, teak benches, tiled floors, tinted windows, and the recent addition of a heater to ward off the winter chill, ensuring that nothing deters the people from smoking. Will they be supplied with air conditioning in the summer? There is no harm in asking!
Setting a Good Example
Tobacco aromas escape, teasing the users of this busy corridor and encouraging people in the Visitor Restaurant who may like the idea of a quick smoke with their coffee… And why not enjoy one with the smoking healthcare professionals who are setting such a good example?
Several months ago I made a suggestion to the management via Occupational Health to provide financial support for women (who form the majority of our hospital personnel) to stop smoking by providing them with free nicotine patches. Unfortunately, this initiative has never seen the light of day (for accounting reasons?). Subsequently, I have been pleased to see that such an initiative had been implemented in Scotland with pregnant women. So it is possible!
Taking the elevator with a caregiver, medic, or other technician whose clothes are saturated with the smell of tobacco smoke never fails to make me cringe. My personal opinion is that it is disrespectful to patients to be confronted with such an unpleasant smell. Some patients suffer from diseases caused by tobacco and struggle to quit — this confrontation is probably even harder for them to tolerate.
Despite having an expensive room reserved for their sole use, smokers also smoke in the gardens. This results in hospitalized patients witnessing the sad spectacle of the “white coats” poisoning themselves with tobacco when they look from their windows or move around the hospital.
First Step Toward a Complete Smoking Ban
We certainly cannot prevent people from smoking any more than we can ban alcohol. However, I know that drinking alcohol in the workplace is prohibited. So why allow smoking in a health facility? Smokers have every opportunity to indulge at home.
The Director and Board of Governors, a majority of whom are American citizens, should remember the American roots of the hospital and ban any form of smoking throughout the hospital including the car parks and gardens. Shouldn’t the first decision be to hand out penalties to smokers who smoke anywhere other than the smoking room?
Pending this initial diktat(!), I am going to put pamphlets on the dangers of smoking from the American Cancer Society on the tables and benches in the smoking room. How many regulars will read it? How long will it stay there?
March 24th, 2015
FDA Grants Premarket Approval to AbioMed Heart Pump
Larry Husten, PHD
The FDA said on Tuesday that it had approved Abiomed’s Impella 2.5 System. According to the company, it is is the first hemodynamic support device to gain FDA approval for use during high risk PCI procedures.
The miniature blood pump is designed for temporary use in patients with severe symptomatic coronary artery disease and diminished (but stable) heart function who are undergoing high-risk PCI but who are not candidates for surgical revascularization. The Impella 2.5 is delivered to the heart through a catheter and pumps blood from the left ventricle into the aorta, helping to maintain heart function and circulation during PCI.
“Use of the Impella 2.5 System is intended to prevent episodes of unstable heart function, including unstable blood pressure and poor circulation, in patients who are at high risk for its occurrence,” said William Maisel, acting director of the Office of Device Evaluation.
The premarket approval (PMA) application was required after the FDA designated the Impella 2.5 System as a class III medical device. The device had been available since 2008 under the less stringent 510(k) premarket notification process. The new approval was based on the PROTECT II clinical study and additional registry data.
The FDA said the device “may allow a longer and more thorough procedure by preventing episodes of hemodynamic instability (e.g., poor circulation, low blood pressure) due to temporary abnormalities in heart function.” Compared to the intra-aortic balloon pump (IABP), the Impella 2.5 System may lead to fewer later adverse events.
The FDA is requiring Abiomed to perform a single arm, post approval study.
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