Linagliptin And Glimepiride Compared In Type Two Diabetes Reply

Sulfonylureas are often added to metformin to improve glycemic control, but at the known risk of increasing hypoglycemia and weight gain. In a report published in the Lancet, more than 1,500 patients with type 2 diabetes taking metformin were randomized to the addition of either linagliptin, a dipeptidyl peptidase-4 inhibitor or the sulfonylurea glimepiride.

After two years the trial achieved the prespecified criterion for noninferiority as treatment with both drugs resulted in a similar effect on HbA1c. Both hypoglycemia and weight gain were reduced in patients taking linagliptin. There was only one case of severe hypoglycemia in the linagliptin group, compared with 12 cases in the glimepridie group. In addition, although there were only a small number of cardiovascular (CV) events, a significant reduction was observed in the linagliptin group.

  • Reduction in mean HbA1c: −0.16% for linagliptin versus −0.36% for glimepiride (difference 0.20%, CI 0.09–0.30)
  • Hypoglycemia: 7% for linagliptin versus 36% for glimepiride (p<0·0001)
  • Weight: −1.4 kg versus  +1.3 kg (p<0·0001)
  •  CV events: 12 vs 26 events, RR 0.46, CI 0.23—0.91 (p=0.0213)

The results, write the authors, “support the use of linagliptin in combination with metformin as a therapeutic option for treatment of type 2 diabetes.”

In an accompanying editorial, André Scheen and Nicolas Paquot discuss the potential benefits of linagliptin and other DPP-4 inhibitors. They note that the smaller reduction in HbA1c with linagliptin “might support the view of a slightly lower efficacy of DPP-4 inhibitors compared with sulphonylureas,” but  say that only a trial with longer followup can assess the durability of of glucose lowering with DPP-4 inhibitors. In the meantime, the effects on weight and the lower rate of hypoglycemia are “important to patients with diabetes” and can improve quality of life.

However, firm conclusions about the drugs can not be reached until long-term trials with cardiovascular outcomes are completed. These trials will “provide enough data for both efficacy (ie, effects on diabetic complications) and safety (ie, concerns about pancreatitis and pancreatic cancer) to draw firm conclusions about the real value of this new approach.”
Click here to read the press release from the Lancet…

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Who Really Won Today? Two Views On Roberts And The Commerce Clause Reply

I had planned to stay out of it. Like every other health care journalist I’ve been following today’s Supreme Court decision, but I have no special expertise in this area and I hadn’t planned  to write about it. But then I became interested in a slightly different angle of the story. An article in Slate by Tom Scocca speculated that although Roberts may have joined the liberal wing of the court and saved the Affordable Care Act, this may actually have been a means to a much larger end, undermining the regulatory powers of Congress under the Commerce Clause.

Writes Scocca: “By ruling that the individual mandate was permissible as a tax, he joined the Democratic appointees to uphold the law—while joining the Republican wing to gut the Commerce Clause…” According to Scocca, this represents “a substantial rollback of Congress’ regulatory powers.” He continues:

Roberts’ genius was in pushing this health care decision through without attaching it to the coattails of an ugly, narrow partisan victory. Obama wins on policy, this time. And Roberts rewrites Congress’ power to regulate, opening the door for countless future challenges. In the long term, supporters of curtailing the federal government should be glad to have made that trade.

Again, this is way our of my area of expertise. So I asked a friend, a former Supreme Court clerk, and, as you will see, a decided liberal, what she thought. Here is her response:

This is, foremost, a big win – or at least avoidance of a big disaster – for Obama & the Democrats (and the country, imho). There were four votes to throw out the ENTIRE ACA – every single element of health care reform – making the biggest single achievement of the Obama administration a nullity, and dooming this country to who knows how many more years without any serious health care reform. We dodged a bullet!

This ruling, upholding the ACA, is the one clear outcome of this case. What result Roberts’ interpretation of the Commerce Clause will have in the future, however, is unclear. It’s true that he endorsed this new idea that “the Commerce Clause doesn’t make people doing nothing enter into commerce,” but I haven’t seen any examples of how that concept could be applied in other cases. (It didn’t really apply in this case, either, because everyone uses the health care system at some point, but whatever.)

- The reality is that, whatever Roberts said today, there are 3-4 consistent votes to strike down almost any Democratic/liberal effort, and to uphold almost any conservative effort. (Someone could say that the same is true in reverse for the court’s liberals.) For the far right on the court, federal power is expansive when you want to stop someone from growing pot, and it’s limited when you want to control people selling guns. I don’t think Roberts’ language today really changes that dynamic. It’s true, if Romney is elected and gets to add another conservative to the Court, they will use Roberts’ language to invalidate all sorts of liberal stuff, but if the language wasn’t there, they would just use something else (or create new precedent).

Bottom line: The result is good news, and that’s what matters.

 

Good Science/Bad Science: Contrasting Papers On Dietary Compositon In JAMA And BMJ 3

Two studies published on Tuesday on dietary composition offer a striking contrast. One tackles the interesting question of whether different diets producing the same amount of weight loss might have different effects on energy expenditure. The investigators performed a rigorous, carefully designed experiment that advances our knowledge about diets and metabolism. The second tackled an even more important question– the long term cardiovascular (CV) impact of different diets. In this instance, however, the investigators relied on weak observational data and reached conclusions that went way beyond anything observational data can provide. One study represents good science. The other does not.

In the first study, published in JAMA, Cara Ebbeling and colleagues carefully studied 21 overweight and obese young adults. After first reaching a 10-15% weight loss during the run-in period of the study, the 21 subjects then received 3 different diets, in random order, for 4 weeks each: a high carbohydrate, low fat diet; a low-glycemic index diet with moderate percentages of carbohydrates and fats; and a very low carbohydrate diet with a high proportion of fat.

Although the subjects received the same amount of calories with each diet, there were significant differences between the groups in the amount of energy burned with the different diets. (This may be an important question, because weight loss requires energy expenditure to be greater than energy intake. If, everything else being equal, diets differ in their effect on energy expenditure, this may lead to superior weight loss strategies.) When compared to baseline, total and resting energy expenditure decreased the most with the high carbohydrate diet and the least with the very low carbohydrate diet. Further, the investigators also found that the low fat diet resulted in an increase in serum leptin levels (which could predict future weight gain) and other factors associated with metabolic syndrome. These same factors decreased with the very low-carbohydrate diet, but were perhaps offset by an incase in CRP levels– a marker of inflammation– with the very low carbohydrate diet.
Click to continue reading…

FDA Approves A New Weight Loss Drug, Breaking a 13 Year Drought Reply

The FDA announced today that it had approved its first new weight loss drug in 13 years. Lorcaserin, which will be sold under the brand name of Belviq, is manufactured by Arena Pharmaceuticals and will be distributed in the US by Eisai.

Lorcaserin is indicated for use in obese adults (BMI 30 or above) or overweight adults (BMI 27 or above) with a coexisting weight-related condition such as hypertension, diabetes, or high cholesterol.

“Obesity threatens the overall well being of patients and is a major public health concern,” said the FDA’s Janet Woodcock, in an FDA press release. “The approval of this drug, used responsibly in combination with a healthy diet and lifestyle, provides a treatment option for Americans who are obese or are overweight and have at least one weight-related comorbid condition.”

The FDA is requiring Arena to conduct six postmarketing studies, including a long-term CV outcomes trial. The label will note that the effect of lorcaserin on cardiovascular morbidity and mortality have not been established  and that its safety and efficacy when used with other weight loss drugs has not been tested.

Arena said that the FDA has recommended to the Drug Enforcement Administration (DEA) that lorcaserin be classified as a scheduled drug. The drug will not be available until after the DEA reviews the recommendation and decides whether the drug will be scheduled. During a press conference the company said that DEA scheduling normally takes from four to six months, indicating that the drug might not become available this year.

Click here to read press releases from the FDA and from Arena/Eisai…

Are Statins Equally Effective In Women And In Men? 1

Jose Gutierrez and colleagues performed a sex-based meta-analysis, seeking to determine if statins yield a similar protective effect on both men and women in preventing recurrent cardiovascular events. In a paper published in the Archives of Internal Medicine, they report the results of their meta-analysis of 11 secondary prevention, double-blinded, placebo-controlled trials, which included 43, 193 patients (11,229 women and 31,962 men).

Overall, statin therapy was associated with a significant reduction in overall CV outcomes for both men and women. For all-cause mortality and stroke, however, the benefit in women did not achieve statistical significance.

All CV outcomes:

  • women: RR 0.81, CI 0.74-0.89
  • men: RR 0.82, CI 0.78- 0.85]

All-cause mortality:

  • women: RR 0.92, CI 0.76-1.13
  • men: RR 0.79, CI 0.72-.87

Stroke:

  • women: RR 0.92, CI 0.76-1.10
  • men: RR 0.81, CI 0.72-0.92

The smaller sample size of women is one possible explanation for the lack of a significant difference in mortality and stroke, according to the authors. Other factors — including the worse cardiovascular profile of women and lower use of antiplatelet agents in women — might also play a role, they speculate.

In an invited commentary, Fiona Taylor and Shah Ebrahim write that it is “misleading” to focus on the lack of statistical significance in women. “The real issue is not significance but whether the effect size in women is materially different from the effect size in men,” they write, and note that “the effect on stroke and all-cause mortality in women is consistent with the effect in men.” They conclude that “statins work just as well in women as in men.”

In an editor’s note, Rita Redberg states that we should not “assume women are the same as men.” She writes that “unless we increase inclusion of women in clinical trials and report sex-specific data, there will never be sufficient data to achieve optimal care of all of our patients.”

Click here to read the Archives press release…

FDA Once Again Delays Approval Of Apixaban (Eliquis) 2

The FDA has once again delayed approval of apixaban (Eliquis), the much-anticipated oral anticoagulant. Bristol-Myers Squibb and Pfizer announced today that it had received a a Complete Response Letter (CRL) to the New Drug Application (NDA) for the drug for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

The two companies reported that the FDA had asked for “additional information on data management and verification from the ARISTOTLE trial”  No new trials were requested by the FDA, according to the companies, who said they “will work closely with the FDA on the appropriate next steps” for the NDA.

Following the widely praised publication and presentation of ARISTOTLE, it was widely anticipated that apixaban would sail through the FDA approval process. This view gained early confirmation when the FDA granted priority review for the NDA last November, but the picture grew cloudier earlier this year when the FDA extended the action date by three months.

Wall Street analyst Tim Anderson speculated that apixaban might still gain FDA approval in 2012, though firm predictions are difficult since Bristol-Myers Squibb and Pfizer have not released details about the questions raised by the FDA in the CRL.

Click here to read the press release from Bristol-Myers Squibb and Pfizer

Olmesartan Use Associated With GI Disorder That Mimics Celiac Disease Reply

A gastroenterologist at the Mayo Clinic has uncovered a rare but potentially serious association between the angiotensin II receptor antagonist (ARB) olmesartan and severe gastrointestinal problems that resemble Celiac disease. The report has been published online in Mayo Clinic Proceedings. In the US, olmesartan is sold as Benicar and, in combination with other drugs, as Azor, Benicar HCT, Tribenzor.

Dr. Joseph Murray first suspected the connection when two patients with refractory Celiac disease experienced symptomatic improvement after discontinuing olmesartan treatment. He eventually identified a total of 22 people over 3 years with unexplained chronic diarrhea and enteropathy who were taking olmesartan. 14 patients had symptoms so severe that they were hospitalized.  All the patients were unresponsive to a gluten-free diet and did not have tissue transglutaminase antibodies in the blood, which are used to detect celiac disease. After discontinuing olmesartan all the patients gained weight and had an improvement in symptoms.

“We thought these cases were celiac disease initially because their biopsies showed features very like celiac disease, such as inflammation,” said Dr, Murray, in a Mayo Clinic press release. “What made them different was they didn’t have the antibodies in their blood that are typical for celiac disease.”

In a statement released on video, Murray emphasized that “the great majority of patients on this medication (olmesartan) do not need to do anything.” However, he recommended that patients taking olmesartan discuss this finding with their physician if they “are experiencing GI symptoms or unexplained weight loss” or “if a diagnosis of celiac disease has been made in the recent past.”

Murray acknowledges that there is currently no evidence demonstrating a cause-and-effect relationship. “We’ve reported an association,” he said. “What needs to be known next is the science to understand why there is such an association.”

Hypertension expert Franz Messerli offered the following comment:
Click to continue reading…

FDA Rejects ACS Indication for Rivaroxaban (Xarelto) 2

The FDA has issued a complete response letter to the supplemental new drug application (NDA) for the proposed indication of rivaroxaban (Xarelto, Johnson & Johnson) in patients with acute coronary syndrome (ACS). The action was expected, since last month the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted against recommending the new indication, which was based on the pivotal ATLAS ACS 2-TIMI 51 trial.

In a press release a J&J company official said the company remains “confident in the robust results of the ATLAS ACS 2 TIMI 51 trial and the positive benefit-risk profile of rivaroxaban in patients with ACS. We will continue to work with the FDA to fully address their questions as quickly as possible.” Rivaroxaban is currently approved for the prevention of clots following knee replacement and hip replacement surgery and for the prevention of strokes and blood clots in people with atrial fibrillation.

Click here to read the press release from J&J…

Guest Post– Reality Check: The ORIGIN of Spin in a Randomized Trial 2

Editor’s Note: The following guest post is reprinted with permission from CardioExchange, the cardiology social media website published by the New England Journal of Medicine. Steven Coca is a nephrologist at the Yale School of Medicine. 

Reality Check: The ORIGIN of Spin in a Randomized Trial

by Steven Coca, DO, MS

In the ORIGIN randomized trial, involving about 12,500 people who had diabetes or were at risk for it, insulin glargine showed no advantage over standard care in preventing the primary composite cardiovascular endpoints at a median follow-up of 6.2 years (see news coverage on CardioExchange). ORIGIN was a completely negative trial, yet in the article’s abstract the authors reported a benefit of basal insulin in the secondary endpoint of incident diabetes (odds ratio [OR], 0.80; 95% CI, 0.64–1.00; P=0.05) and stated that the treatment “reduced new-onset diabetes.” The discussion section of the paper further asserted that the treatment “slowed progression of dysglycemia.”

A few qualifications are in order:

1. This seemingly positive finding (in incident diabetes) was for only one of several secondary endpoints, and the alpha level needed to detect a difference was not corrected for multiple outcome assessments.

2. Among the 1456 participants without diabetes at randomization, only 44% of insulin glargine recipients and 47% of standard-care recipients underwent both prespecified oral glucose tolerance tests at the end of the study. So, in effect, fewer than half of the patients were assessed on the one, barely positive endpoint of incident diabetes. Plus, the fact that an absolute 3% more of the control group underwent the necessary testing could have resulted in ascertainment bias.

3. Incident diabetes among those 1456 participants was much greater than 10% (30% in the insulin glargine group, 35% in the standard-care group), but the authors reported an odds ratio rather than a relative risk, yielding an overinflation of the purported benefit  The relative risk would have been 0.86, compared with the reported OR of 0.80. (Only when the probability of a disease is low does the odds ratio approximate the relative risk.)

4. The upper boundary of the confidence interval included 1.00.

Despite these realities, Sanofi and the investigators didn’t hesitate to “spin” the trial findings to the media. The Sanofi press release stated, “…the results also showed that insulin glargine delayed progression from pre-diabetes to type 2 diabetes.” Sanofi’s VP of Medical Affairs said, “ORIGIN shows that it is possible to maintain low and stable HbA1c levels that are close to normal over a long time, and to potentially delay the progression from pre-diabetes to diabetes.” One of the lead investigators took this positive angle: “We know that in this study, insulin lowered blood sugar levels and did so safely and effectively. I can look at a patient and say, ‘Your blood sugar is not well controlled right now, so let’s go ahead and add insulin’.”

There is a temptation for those involved in a trial to present findings as positive, even if the positive aspect is only a morsel. However, scientists should stick to the facts. The first sentence of the abstract of this paper asked whether “the provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events.” The results of the trial tell us that the answer is simply “No.”

How did you read the ORIGIN trial? What’s your take on the facts versus the spin?

New Uses Found for a Traditional Walking Test 1

(Updated at bottom)– The 6-minute walk test (6MWT) can improve risk prediction in people with stable coronary disease, according to a new study published in Archives of Internal Medicine. The 6MWT may also be cost-effective and, in addition, may help physicians motivate their patients to exercise, suggest the authors.

Alexis Beatty and colleagues performed a 6MWT and a treadmill exercise test in 556 people with stable coronary heart disease. After a median followup of 8 years, cardiovascular (CV) events had occurred in 39.2% of the study participants.

Compared to people in the highest quartile of walking distance (544-837 m), people in the lowest quartile of walking distance (87-419 m) had 4 times the risk of a CV event during followup.

  •  Unadjusted hazard ratio: 4.29, CI 2.83-6.53, p < .001

After adjustment for other factors, each 104 m decrease in walking distance (1 standard deviation) was associated with a 30% increase in CV events (HR 1.30,CI 1.10-1.53). The 6MWT was similar to the treadmill exercise test in predicting CV events.

The authors wrote that treadmill testing is still preferable for evaluating patients with suspected ischemia, but they noted a number of advantages of the 6MWT in stable patients:

The 6MWTcan be conducted with little equipment other than a hallway marked for distance and a stopwatch. Due to the self-paced nature of the test, adverse events of chest pain, dyspnea, or musculoskeletal pain are usually mild; serious adverse events have not been described. Furthermore, the 6MWT is less expensive than treadmill exercise testing, especially if stress testing is bundled with imaging that may be unnecessary.

Furthermore, the 6MWT can be used to motivate patients to exercise:

Despite evidence demonstrating the efficacy of exercise-based rehabilitation in patients with CHD for reducing mortality, most patients do not participate in cardiac rehabilitation or achieve recommended levels of physical activity. There is a need for improved strategies to identify patients at the greatest risk of cardiovascular events and to motivate patients and physicians to address physical activity as a modifiable risk factor. Repeated measurement of the 6MWT could be used as a simple office-based tool to monitor exercise capacity and motivate patients to achieve appropriate levels of physical activity. Although we demonstrated that the 6MWT can predict cardiovascular events in stable CHD, its use for improving prognosis merits further study.

In an accompanying comment, David Nash agrees with the investigators and recommends “that physicians interested in improving their patients’ level of fitness use the 6MWT as a means of getting the patient started on regular exercise. Once the patients become familiar with the ease and safety of the 6MWT, they can be encouraged to repeat the 6MWT more frequently, even on a daily basis. It is then possible to lengthen the walk at appropriate intervals.”

Comment:

Perhaps I’m overreacting but I think this is a great paper in its own modest way. Unlike so many of the studies I write about I can’t find even a hint of bias, distortion, or gamesmanship. The authors proposed a promising hypothesis, carefully analyzed their results without resorting to data dredging or statistical trickery, and reported the results in a clear and concise manner, always keeping in mind the practical, real-world effect of their work. The authors are academics but this does not appear to be a paper written solely to placate a sponsor, gain publication credit, or display intellectual fireworks.

The absence of any commercial interest or motivation is particularly refreshing, except insofar as the subject of the paper, the 6-minute walk test, may actually save money by offering an inexpensive alternative for suitable patients to the more expensive treadmill exercise tests (and the much more expensive imaging procedures that so often accompany treadmill tests). Further, as the authors and the editorialist observe, the 6-minute walk tests has a rare virtue, in that it secretly performs double duty, not only improving prognostication but supporting the much-needed therapeutic task of starting and encouraging patients to exercise.

These facts shouldn’t be remarkable or unusual in any way. It’s a sad commentary on so much of the medical literature that they are.

Update– Perhaps it’s belaboring the obvious, but I think we should ask why there aren’t more studies like this, and why professional societies and other institutions don’t offer more CME activities to assist physician implementation of these kinds of strategies in clinical practice. Successful introduction of an exercise program in a population at high risk for CV events would almost certainly have a greater impact on outcomes than the various strategies that have been the subject of the myriad ongoing debates in the cardiology community involving drugs versus devices, more drugs versus less drugs, drug A versus drug B, drug A + B versus drug A + B+ C, device X plus drug A versus device Y plus drug B, etc etc ad nauseum.

Imagine if we could devote even a small portion of the intellectual energy and practical resources now devoted to drug and device development to research in exercise and nutrition. The common response to advocates of lifestyle-based therapies is that they don’t work in most people. But remember: the vast majority of drugs don’t work either, and even the most successful drugs and devices require an enormous concentration of resources to bring them successfully to market. Wouldn’t it be great if we could try the same thing with something as simple as exercise?

 

Is Chronic Kidney Disease A CHD Risk Equivalent? Reply

A new study published in the Lancet provides new data about whether chronic kidney disease (CKD) should, like diabetes, be considered a coronary heart disease (CHD) risk equivalent.

Marcello Tonelli and colleagues analyzed data from a population of 1.25 million people in Alberta, Canada. During a median followup of 4 years, 11,340 people were admitted to the hospital for MI. People with a previous MI were at higher risk for MI admission than people with either diabetes or CKD:

  • MI history: 18.5 per 1000 person-years (CI 17.4–19.8)
  • Diabetes: 5.4 per 1000 person-years (5.2–5.7)
  • CKD: 6.9 per 1000 person-years (6.6–7.2)
After adjustment for other variables, the relative rate of MI was lower in the CKD group than in the diabetes group (rate and adjusted relative rate for MI admission):
  • Previous MI: 7.7%, RR 3.8 (CI 3.5-41)
  • Diabetes and CKD: 6%, RR 2.7 (2.5-2.9)
  • CKD: 2.8%, RR 1.4 (1.3-3.5)
  • Diabetes: 2.4%, RR 2.0 (1.9-2.1)
  • No diabetes or CKD: 0.5%, RR 1 (reference)

The authors write that their “data show that diabetes alone and chronic kidney disease alone… do not increase the rate of myocardial infarction to the same extent as does a history of coronary disease, and therefore do not support the use of the term coronary heart disease risk equivalent for either disorder.” However, they concluded that CKD should “be added to the list of criteria defining people at highest risk of future coronary events.”

In an accompanying comment, Tamar Polonsky and George Bakris write that “despite negative findings for the primary outcome, compelling reasons are provided to consider lipid-lowering therapy in patients with chronic kidney disease.”
Click here to read the Lancet press release…

The Grim Impact of Loneliness And Living Alone Reply

Two new reports published in the Archives of Internal Medicine throw a spotlight on the grim effects of loneliness and living alone on health.

As part of the Health and Retirement Study, 1604 people were followed for 6 years after answering a questionnaire about loneliness. Some 43% reported feeling lonely. Loneliness was associated with significantly increased risks for death and other adverse outcomes:

  • Death: 22.8% vs. 14.2%, adjusted risk ratio (RR) 1.45, CI 1.11-1.88
  • Decline in activities of daily living: 24.8% vs. 12.5%, RR 1.59, CI 1.23-2.07
  • Difficulty with upper extremity tasks: 41.5% vs. 28.3%, RR 1.28, CI 1.08- 1.52
  • Decline in mobility: 38.1% vs. 29.4%, RR 1.18, CI 0.99-1.41
  • Difficulty with climbing: 40.8% vs. 27.9%, RR 1.31, CI 1.10-1.57

The authors of the study recommend that physicians ask their patients about loneliness so that they “will be better able to target interventions intended to prevent functional decline and disability.”

In the second study, investigators from the REduction of Atherothrombosis for Continued Health (REACH) Registry analyzed data from 44,573 individuals, 8594 of whom were living alone. This group had significantly higher risks for death and cardiovascular death than those not living alone (p<0.01):

  • 4-year mortality: 14.1% vs. 11.1%
  • CV death: 8.6% vs. 6.8%

In an invited commentary, Emily Bucholz and Harlan Krumholz (who is also editor-in-chief of CardioExchange) discuss the myriad difficulties and complexities involved in understanding and employing social support. Scientists, they write, should be “challenged to investigate mechanisms as well as practical interventions that can be used to address the social factors that undermine health.”

Click here to read the press release from Archives…

Guest Post: Industry editorial makes outlandish claim about impact of medical devices 2

Editor’s Note: The following guest post by Gary Schwitzer is reprinted with permission from HealthNewsReview blog, an indispensable resource for tracking the best and worst of healthcare journalism.

Industry editorial makes outlandish claim about impact of medical devices

by Gary Schwitzer

Minnesota is the home of several medical device makers.  So there’s been a lot of editorializing about the medical device tax in the Affordable Care Act. There has been some criticism of Minnesota politicians over whose interests they represent on the issue.

Today’s Star Tribune carries a commentary from an industry spokesman – Dale Wahlstrom, president and CEO of LifeScience Alley. He retired from Medtronic in 2006 after 24 years.  His commentary includes this claim:

Medical devices save and improve lives. Between 1980 and 2000, medical device technology slashed the death rate from heart disease by a stunning 50 percent and cut the death rate from stroke by 30 percent. As a result, life expectancy was extended by more than three years.

Please note: I’ve written to a contact at LifeScience Alley asking for the source of that data.  In fairness, he hasn’t had much time to respond but I don’t expect an answer on the data source because I don’t think there is one. I’ll be happy to post an amendment/addendum if/when an answer is forthcoming. That editorial has been published for hours already and I think it’s important to publish even this quick analysis as quickly as I can.

This quote attributes ALL cardiovascular health improvements to devices rather than siphoning off the mere fraction that might be attributable to devices versus drug therapies versus lifestyle changes.

One analysis published in the New England Journal of Medicine concluded:

Approximately 47% of this decrease (in coronary disease death rate) was attributed to treatments, including secondary preventive therapies after myocardial infarction or revascularization (11%), initial treatments for acute myocardial infarction or unstable angina (10%), treatments for heart failure (9%), revascularization for chronic angina (5%), and other therapies (12%). Approximately 44% was attributed to changes in risk factors, including reductions in total cholesterol (24%), systolic blood pressure (20%), smoking prevalence (12%), and physical inactivity (5%), although these reductions were partially offset by increases in the body-mass index and the prevalence of diabetes, which accounted for an increased number of deaths (8% and 10%, respectively).

So a little less than half is attributable to changes in risk factors.  A little more than half to ALL treatments – including drugs, surgery, etc.

The largest reductions in deaths came from the use of secondary-prevention medications or rehabilitation after acute myocardial infarction or after revascularization (a total reduction of approximately 35,800 deaths) and from the use of initial treatments for acute myocardial infarction or unstable angina (approximately 35,145 deaths), followed by treatments for heart failure and hypertension, statin therapy for primary prevention, and treatments for chronic angina.

The editorial is more than a matter of playing loose with the numbers; it is a vast overstatement and a distortion of the evidence. There’s no question that medical devices have contributed to the decline.  It is disingenous to attribute ALL of the benefit to devices.

I’m not going to comment on the medical device tax.  For now, I’ll leave that to the politicians and special interests.

But on this site, we address and try to correct any misleading claims about medical interventions whenever we see them – whatever the source.  And this editorial made a whopper!

I only hope that such whopping misleading claims aren’t misleading politicians into positions they wouldn’t take if they evaluated the claims.

FDA Advisory Panel Recommends Expanded Indication For Sapien Transcatheter Heart Valve Reply

The FDA’s Circulatory System Devices Panel voted overwhelmingly on Wednesday to recommend an expanded indication for the Edwards Sapien Transcatheter Heart Valve in patients with symptomatic severe aortic stenosis who have high operative risk. The device is currently approved for use only in patients who are not surgical candidates.

The committee voted 10-2 that the Sapien device was safe, 12-0 that it was effective, and 11-0, with 1 abstention, that the benefits of the device outweigh the risks. Much of the day was spent by committee members wrestling with a number of difficult questions raised by FDA reviewers prior to the meeting, including the possible introduction of bias in the pivotal PARTNER A trial  because some patients randomized to surgery did not undergo surgery, the difficulty of evaluating the transapical approach due to the small number of patients randomized in that stratum of PARTNER, and the higher incidence of stroke and aortic regurgitation in the Sapien group.

Ultimately, however, the committee was persuaded by the totality of the data from PARTNER and additional nonrandomized data from patients who received the device under a continued access protocol. An additional strong source of reassurance for the panel was the safeguard provided by the TVT registry, a joint initiative from the Society of Thoracic Surgeons (STS) and The American College of Cardiology (ACC) that will closely monitor the use of TVR in clinical practice.

In sharp contrast to many recent advisory committee meetings, this panel was marked by the absence of drama and tension. A high point of the meeting for many observers was the public comment session. One speaker was a 92-year-old Sapien recipient who was a World War II veteran and prisoner or war who had survived the Bataan Death March. Another patient who spoke in favor of Sapien was the father of well-known Columbia University interventional cardiologist Jeffrey Moses, who helped develop the device. Moses said that he “wisely” chose to stay out of the case, though initially he did help persuade his father to accept the device after he refused to undergo surgery.

Related reading: 

Live Blog: FDA Advisory Panel For Edwards Sapien Transcatheter Heart Valve Reply

Here’s my live-blog of the FDA’s meeting of the Circulatory System Devices Panel to consider the premarket approval (PMA) application for the Edwards Sapien Transcatheter Heart Valve for use in patients with symptomatic severe aortic stenosis who have high operative risk. As reported here earlier this week, FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart valve system. Here is a link to the FDA and Edwards briefing documents.

============================================

Meeting adjourned.

6:00– The committee votes 10-2 that Sapien is safe, 12-0 that it is effective, and 11-0 (1 abstention) that the benefits outweigh the risks. 

5:55– Here’s questions 2 and 3:

VOTING QUESTION 2: Is there reasonable assurance that the Edwards SAPIENTM Transcatheter Heart Valve is effective for use in patients who meet the criteria specified in the proposed indication?

VOTING QUESTION 3: Do the benefits of the Edwards SAPIENTM Transcatheter Heart Valve for use in patients who meet the criteria specified in the proposed indication outweigh the risks for use in patients who meet the criteria specified in the proposed indication?

5:54– Wow– computer voting system is broken! They’re going to vote on paper.

5:48– After they finish the legal mumbo jumbo the voting will begin.

5:43– Getting close to the voting questions. Here’s #1:

VOTING QUESTION 1: Is there reasonable assurance that the Edwards SAPIENTM Transcatheter Heart Valve is safe for use in patients who meet the criteria specified in the proposed indication?

5:39– Edwards via Craig Smith giving their summary. He says he’ll be brief.

5:38– Now talking about study data that should be included in the labeling.

5:30– Now talking about post-approval studies to get further insights into stroke, aortic regurgitation, long term effectiveness, valve-in-valve, and gender issues.

5:28– Now discussing the totality of the evidence. Chairman states that the committee agrees that Sapien is safe and effective, with a number of caveats, such as stroke, TA/TF, gender, AR. (Why bother voting now?)

5:20– Committee now discussing informed consent and whether a more detailed informed consent form should be required. An additional piece of paper is not really the ideal solution.

5:15– Chairman summarizes that the FDA is concerned that valve-in-valve use may occur, but there’s no data to support this. Committee strongly encourages getting data on this and it should not be endorsed on the label. Committee wants to motivate the company to perform a separate clinical trial for this indication.
Click to continue reading…

Single Case Report Casts New Doubts About St. Jude Durata ICD Leads 1

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

As if on cue, just as the train pulled into the Nice-Ville station for this week’s Cardiostim 2012 meeting on the French Riviera, my Twitter stream and email lit up with news about a MAUDE case report about an externalized Durata:

Non invasive programmed stimulation of icd, revealed undersensing of ventricular fibrillation after induction. Fluoroscopy of lead revealed externalization of conductors. The externalization was confirmed at lead extraction. The externalization was adjacent to the distal coil of the lead.

Wall Street reacted promptly with a 6% drop in St. Jude’s stock price on Tuesday.

Though not widely reported, this was not the first report of an externalized Durata. As I reported previously, at the Riata Lead Summit in Minneapolis in January, St. Jude presented a case of a patient in Alaska with an externalized Durata lead.  At that point, the company was able to dampen negative reaction with an analysis indicating that the externalization was caused by abrasion of the lead in an “outside-in” fashion from contact with a tricuspid valve annuloplasty ring.

Why did this new Durata story provoke such a strong reaction?

• The new MAUDE report arrived without any explanation or reaction from St. Jude Medical.  The first references came from the financial analyst community and filtered out through online sources such as Twitter and Cafepharma.com.  There have been no additional details beyond the brief summary in MAUDE .  St. Jude Medical seemed to be as surprised as everyone else. A St. Jude spokesperson told Reuters: “We will make every effort to learn more about the report as quickly as possible.”

• This is the first important new development since last month’s Heart Rhythm Society Meeting in Boston.  At that meeting, as reported in Med City News, Charles Love of Ohio State, offered a favorable perspective on Durata. This was counterbalanced by unfavorable data about the prior generation Riata lead and a scathing commentary by ICD watchdog Robert Hauser, as I then reported.

• The report comes on the eve of the Cardiostim Meeting here in Nice.  This meeting serves as a European counterpart to last month’s HRS sessions and will provide a ready forum for reaction and consensus building.

• St. Jude has waged an aggressive defense of Durata, promoting “0% Externalized Conductors” in promotional materials (see photo at bottom).  This “all-in” stance may have created lofty expectations for this lead’s performance.  Even a single unsubstantiated case report therefore could create an unfavorable reaction.

It remains to be seen if this case report will be the “tip of the iceberg” or an isolated phenomenon. Its validity is even being questioned, as FDA cannot reveal its source and the details of the report have not yet been made available.

Those of us who have followed medical device failures closely over the years should know not to react too quickly to case reports.  It seemed inevitable to me that there would be at least some Durata externalization reports given that lead’s similarity in design to the Riata ST lead. However, a single case report, or even a few cases reports, do not provide sufficient evidence to indict Durata at this time.  More information may arrive soon in the form of an expected paper from Dr. Hauser on Durata electrical failures in the MAUDE database.

(Photo of Durata promotional truck at HRS courtesy of Dr. Wes)

ACC Releases Appropriate Use Criteria For Noninvasive Peripheral Tests Reply

The American College of Cardiology (ACC) has published appropriate use criteria (AUC) for peripheral vascular ultrasound and physiological testing. The criteria were developed in coordination with 10 other medical societies.

“This is the first systematic and comprehensive evaluation looking at appropriate indications for vascular testing, such as ultrasound or functional testing,” said Emile Mohler III, the chair of the writing committee, in an ACC press release. “We hope this document will help clinicians determine whether or not and when to refer individual patients for testing.”

The 19 members of the panel identified common clinical situations in which noninvasive vascular testing is often considered and then assessed the appropriateness of each indication. In half of the scenarios testing was deemed to be appropriate. In general, tests were considered appropriate when they were prompted by clinical signs and symptoms.

About 20% of scenarios were judged inappropriate. Here are examples cited by the ACC in the press release:

  • Ordering an ultrasound of the carotids or neck arteries in someone at low risk for heart attack or stroke.
  • Screening for kidney artery disease in someone with peripheral artery disease with well controlled high blood pressure (hypertension) on one medication
  • Choosing to perform an abdominal ultrasound in a patient with non-specific lower extremity discomfort
  • Ordering a mesenteric artery ultrasound (arteries that supply the small and large intestines) as an initial test to evaluate the patient with chronic constipation or diarrhea
  • Performing a follow-up study for a patient with a normal baseline study who has no new symptoms

Click here to read the press release from the ACC…

Basal Insulin And Omega-3 Fatty Acids Fail To Improve Outcomes In Diabetics And Prediabetics Reply

A large new study has found no evidence of cardiovascular (CV) benefits for either basal insulin or omega-3 fatty acids in a population of people with diabetes or at risk for diabetes. Results of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) study were presented on Monday at the annual meeting of the American Diabetes Association and published simultaneously in two separate papers in the New England Journal of Medicine.

In a 2 x 2 factorial design, more than 12,500 patients with impaired fasting glucose, impaired glucose tolerance, or diabetes were randomized to either insulin glargine or standard care and to either omega-3 fatty acids or placebo. After a median followup of 6.2 years there were no significant differences in outcomes in either of the randomizations.

Insulin glargine versus standard care:

  • Nonfatal MI, nonfatal stroke, or CV death: 16.6% versus 16.1% (hazard ratio, 1.02, CI 0.94 – 1.11, p = 0.63)
  • Nonfatal MI, nonfatal stroke, CV death, revascularization or HF hospitalization: 28.6% versus 27.5%, HR 1.04, CI 0.97 – 1.11, p = 0.27)

People taking insulin glargine were more likely to gain weight and develop hypoglycemia, but had better glucose control than people receiving standard care. Patients without diabetes at baseline receiving insulin were less likely to progress to diabetes. There was no difference in cancer between the two groups.

The ORIGIN investigators noted that the glycemic benefit of insulin glargine might have an impact on microvascular or other outcomes but concluded that the trial does “not support changing standard therapies for early dysglycemia.”

Omega-3 fatty acids versus placebo:

  • CV death (primary endpoint): 9.1% versus 9.3% (HR 0.98, CI 0.87 – 1.10, p = 0.72)
  • Major vascular events: 16.5% versus 16.3% (HR 1.01,CI 0.93 – 1.10, p = 0.81)
  • Death from any cause: 15.1% versus 15.4% (HR 0.98, CI 0.89 – 1.07, p = 0.63)
  • Death from arrhythmia: 4.6% versus 4.1% (HR 1.10, CI 0.93 – 1.30, p = 0.26)

The authors cautioned that their ” findings may not be relevant to dietary recommendations to consume more fish, because dietary change not only increases the intake of foods containing n–3 fatty acids but is also associated with a reduction in the consumption of foods such as red meats, which may be harmful.”

Click here for the press release from Sanofi…

FDA Reviewers Raise Questions About Sapien Heart Valve System 1

FDA reviewers have raised a number of questions about the safety and efficacy of the Sapien heart valve system. The review was published online ahead of Wednesday’s meeting of the Circulatory System Devices Panel meeting to evaluate the Sapien system for use in patients eligible but at high risk for aortic valve surgery. The Sapien system was previously approved in November 2011 for patients not considered surgical candidates for aortic valve replacement.

The FDA briefing document cites numerous examples of possible bias in the pivotal PARTNER A trial. The most serious problem appears to be caused by the high number of patients randomized to surgery who did not undergo surgery, including 7.9% who refused treatment or withdrew from the study. By contrast, only 0.3% of TAVR patients refused treatment or withdrew from the study. Surgical patients were also more likely to receive concomitant operations, another possible source of bias.

Another important topic of discussion will undoubtedly be the differences in outcome between patients receiving the transapical (TA) and transfemoral (TF) approaches. Unlike the TF stratum, where mortality was lower in the Sapien group, in the TA stratum mortality was higher in the Sapien group. Because there were only a relatively small number of patients in the TA group in the PARTNER trial, the panel will also consider TA patients treated outside the context of randomized trials.

The FDA reviewers were also concerned about stroke and aortic regurgitation. In the first 30 days the stroke rate was doubled in the Sapien group, and there were more strokes overall in the Sapien group in the TA stratum. Concern was also raised about the 53% of Sapien-treated patients who had mild or greater aortic insuficiency.

One interesting point raised by the FDA is that transcatheter aortic valve replacement (TAVR) is not nearly as noninvasive as many have been led to believe:
Click to continue reading…

Transient Glucose Regulation Helps Prevent Progression To Diabetes In Prediabetics Reply

Prediabetics– people with impaired fasting glucose or impaired glucose tolerance– can reduce their high risk of progressing to diabetes if they achieve even a transient return to normal glucose regulation, according to results of the Diabetes Prevention Program Outcomes Study (DPPOS), presented at the American Diabetes Association meeting and published simultaneously online in the Lancet.

Leigh Perreault and colleagues in the Diabetes Prevention Program Research Group analyzed data from 1,990 participants who had been randomized in the original DPP study to either intensive lifestyle intervention, metformin, or placebo. The risk of developing diabetes was significantly lowered by 56% in the study subjects who at some point during the DPP study had normal glucose regulation compared with those who continued to have prediabetes (hazard ratio 0.44, CI 0.37–0.55, p<0.0001). Diabetes prevention was strongly correlated with the number of times subjects were found to have normal glucose regulation.

For diabetes prevention it didn’t matter to which treatment group people were assigned if they attained normal glucose regulation at some point. However, people randomized to intensive lifestyle intervention who remained consistently prediabetic were more likely to develop diabetes.

The investigators wrote that the results of their study suggest “that the strategy is unimportant as long as the intervention is early (when someone has prediabetes) and can restore normal glucose regulation, even if transiently. Further, maintenance of prediabetes despite the potent glucose-lowering effects of intensive lifestyle modification represents a high-risk state and might warrant additional preventive strategies.”

In an accompanying comment, Natalia Yakubovich and Hertzel Gerstein write that “identification of regression to normoglycemia could be an important way to stratify people into those at higher and lower risk of progression to diabetes. Such stratification could therefore identify individuals for whom additional treatment might be needed to prevent diabetes or to slow down disease progression.”
Click here to read the Lancet press release…

Growing Popularity Of Dabigatran Leads To Increased Complications 1

Since its approval in the United States in October 2010 dabigatran (Pradaxa) has been prescribed 3.2 million times to more than 600,000 patients with nonvalvular atrial fibrillation (AF), according to its manufacturer, Boehringer Ingelheim. The company also announced that, based on the pivotal RE-LY trial, the “Clinical Studies” section of the drug’s prescribing information now includes the statement that 150 mg twice daily of dabigatran “was superior in reducing ischemic and hemorrhagic strokes relative to warfarin.”

But the news about dabigatran is not entirely upbeat. According to new data compiled by QuarterWatch (PDF), in 2011 the FDA received more safety reports about dabigatran than any other drug. The data are not entirely unexpected, since the bleeding complications of dabigatran are well known and physicians are more likely to report adverse events associated with new drugs. The drug that dabigatran was designed to replace, warfarin (Coumadin), was the second most reported drug, and has been high on the FDA list for many years.

Dabigatran was the subject of  3,781 serious adverse events reported to the FDA in 2011. This included 542 patient deaths and 2,367 hemorrhages. Warfarin  was the subject of  1,106 serious adverse events, including 72 deaths.

QuarterWatch noted that the difference between the two anticoagulants “could be at least partly explained by differences in the reporting rate for an older generic drug with many manufacturers, and a newly launched brand name drug being promoted by a large sales force.” But, according to QuarterWatch:

“What is clear, however, is that the FDA’s system is receiving a strong signal about this safety issue. A large share of dabigatran reports (79%) come from health professionals, suggesting that despite this well-known drug risk the bleeding was unexpected or unusually severe.”

QuarterWatch notes that the rapid uptake of dabigatran is probably due to its ease of use– no frequent INR tests are required– and the lack of drug interactions. One likely source of complications is the use of the standard 150 mg dose in older patients or those with renal dysfunction. The label now recommends that physicians “assess renal function during therapy as clinically indicated” but QuarterWatch wonders “whether this modest language will lead to safer use.”
Click here to read the Boehringer press release…

Real World Bleeding Risk Of Aspirin In Primary Prevention Examined Reply

A new study published in JAMA provides substantial new evidence about the real world effects of aspirin, including the risk of  bleeding, in a broad  population. The study also sheds important new light on the effects of aspirin in a diabetic population.

Giorgia De Berardis and colleagues analyzed data from more than 4 million people in Puglia, Italy and compared 186,425 people taking low-dose aspirin with the same number of matched controls not taking aspirin.

Major bleeding events requiring hospitalization:

  • aspirin: 5.58 (5.39-5.77) per 1000 person-years
  • controls: 3.60 ( 3.48-3.72) per 1000 person-years
  • Incidence rate ratio (IRR) 1.55 (1.48-1.63)

Diabetics overall had an increased risk of major bleeding episodes but this increased risk was not significantly associated with aspirin use:

  • Hemorrhagic events in diabetics overall (compared with non diabetics): IRR 1.36 (1.28-1.44)
  • Hemorrhagic events in diabetics taking aspirin compared with diabetics not taking aspirin: IRR 1.09 (0.97-1.22)

The authors wrote that their findings demonstrate that bleeding events occur more frequently than had been observed in clinical trials. They calculated that for individuals with a 10-year risk of cardiovascular events between 10% and 20% the risks and benefits of aspirin therapy are similar, causing 2 excess bleeds, and preventing 2 CV events, for every 1,000 people treated each year.

In an accompanying editorial, Jolanta Siller-Matula writes that the benefits of aspirin in secondary prevention are “not disputed,” since aspirin can prevent 6 major vascular events at the expense of 1 major bleeding event. But there is no such consensus for primary prevention, and Siller-Matula writes that the findings of the Italian study reinforce current European guidelines which do not recommend aspirin for primary prevention.

The JAMA study provides far more information about aspirin use in diabetics than had been previously available. Nevertheless, writes Siller-Matural, the decision whether to use aspirin for primary prevention in this population is still not clear, and will require additional data from ongoing studies.

Click here to read the JAMA press release…

Troponin T Test Helps Assess Risk Following Noncardiac Surgery Reply

A new study in JAMA finds that postoperative Troponin T (TnT) tests can independently improve 30 day mortality risk assessment among patients who have had noncardiac surgery.

The VISION (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation) study investigators evaluated the prognostic power of postoperative fourth-generation TnT testing in 15,133 patients. Overall mortality at 30 days was 1.9%.

11.6% of patients had peak TnT values greater than 0.02 ng/mL. These patients had an increased risk of death at 30 days:

  • TnT < 0.01: 1% mortality at 30 days
  • TnT 0.02 ng/mL: 4%, adjusted hazard ratio 2.41 (1.33-3.77)
  • TnT 0.03-0.29 ng/mL: 9.3%, HR 5.00 (3.72-6.76)
  • TnT > 0.30: 16.9%, HR 10.48 (6.25-16.62)
The VISION investigators reported that TnT was the strongest predictor of 30-day mortality. A population attributable risk analysis found that 41.8% of deaths were explained by elevated TnT levels. The findings suggest that postoperative patients with elevated TnT levels may benefit from aspirin and statin therapy, but this strategy has not been tested in clinical trials, the authors note. The investigators concluded that “clinical trials are needed to establish whether interventions can alter patients’ risk of death based on an elevated troponin measurement after surgery.”
Click here to read the press release from JAMA…

Subway Meals Get American Heart Association Endorsement 2

The American Heart Association (AHA) announced today that it had initiated a new program that it claims will help people choose healthy meals at restaurants. The Subway restaurant chain will be the first to display the Heart-Check Meal Certification logo next to certain selected meals.

In a press release the AHA’s president, Gordon Tomaselli, said the program would make “it easy for consumers to make smart choices that are heart-healthy when eating outside the home, knowing they often don’t have the benefit of reviewing the nutrition facts.” The meal certification program is an expansion of the AHA’s Heart-Check Food Certification program, which was established in 1995.

Tomaselli told USA Today that certification can cost companies as much as $700,000 annually. “But it’s not pay-to-play,” he told the paper. “The money is used to make sure what we’re telling the public is correct.”

The AHA certification logo will be displayed on Subway meals that meet the AHA’s nutritional criteria for levels of sodium, calories, cholesterol, saturated fat and trans-fats. But the new program does not mean that all meals certified by the program will necessarily be heart healthy, as noted on the Heart-Check Meal Certification webpage:

Is it still heart healthy to order my meal with mayonnaise or mustard?

  • The standard SUBWAY® 6-inch sandwiches that are part of the AHA (adult) certified meal are prepared on 9-grain wheat bread and contain the following vegetables: lettuce, tomatoes, onions, green peppers and cucumbers.
  • These sandwiches were evaluated without the addition of condiments such as mustard or mayonnaise. Adding condiments containing sodium (such as mustard) or fat (such as mayonnaise) may result in the meal no longer meeting AHA meal criteria.
  • Condiments such as mayo and mustard add saturated fat, sodium and cholesterol that can easily be avoided. These small choices throughout the day can help keep eating habits on track.
  • Additions such as pickles, cheese, and olives also make the sandwich less healthy.
  • Considering the freshness of the bread and the flavor and juiciness provided by the vegetables, these sandwiches are tasty without the addition of other toppings or condiments.

Subway said that it had been an AHA supporter for 12 years. On the AHA website, Subway is listed as a member of the Industry Nutrition Advisory Panel (INAP). Here is the mission of the INAP, according to the AHA website:

The American Heart Association (AHA) Industry Nutrition Advisory Panel (INAP) is a strategic relationship between the AHA Nutrition Committee and food industry leaders. INAP provides a platform for sharing information and planning cooperative programs in the areas of diet and nutrition and cardiovascular disease.

INAP industry members pay a $10,000 yearly membership fee to participate in meetings with “science representatives” from the AHA and other industry members. Here is the AHA description of the benefits of membership:

The primary benefit of INAP is bringing together industry and science representatives to exchange dialogues on areas of mutual interest pertaining to nutrition. Benefits of this dialogue include:

  • Networking and relationship building with industry leaders
  • Education on relevant topics from the nutrition, physical activity, metabolism and obesity areas
  • Members get the latest updates on all AHA initiatives and are given the opportunity to provide input to the AHA regarding statements and positions on these topics
  • Direct access to AHA staff involved in nutrition-related issues
  • An organized relationship with the Nutrition Committee that allows for open communication on topics of interest

Members also receive one complimentary registration to attend the AHA’s spring science conference and council dinner coordinated by the Nutrition, Physical Activity and Metabolism Council (NPAM) and the Council on Epidemiology (EPI).

In addition to Subway, some of the other members of INAP are Uniliver, Coca-Cola, Dr. Pepper, Frito-Lay, Hershey, Kellog, Kraft, McDonald’s, Sara Lee, The Sugar Assocaition, Welch’s, and Yumi Brands (Taco Bell, KFC, Pizza Hut).

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Observational Study Finds Possible Long-Term Mortality Advantage for Rhythm Control Drugs In Atrial Fibrillation Reply

Challenging a decade-old influential trial, a large observational study of patients with atrial fibrillation (AF) suggests that rhythm control drugs may outperform rate control drugs after 4 years.

Raluca Ionescu-Ittu and colleagues analyzed data from 26,130 patients 66 years or older diagnosed with AF in Quebec, Canada. Patients were followed for a mean of 3.1 years and for a maximum of 9 years. In apparent agreement with the AFFIRM trial, the investigators observed a small early increase in mortality associated with rhythm control therapy, followed by similar mortality between the groups until year 4. After year 4, however, mortality was lower in the rhythm control arm.

Total unadjusted mortality

  • Rhythm control: 48.3%
  • Rate control: 50.1%

Unadjusted mortality at 5 years:

  • Rhythm control: 41.7%
  • Rate control: 46.3%

Adjusted hazard ratios for rhythm control at:

  • 6 months: 1.07 (1.01-1.14)
  • 1 year: 1.03 (0.95-1.11)
  • 3 years: 0.95 (0.90-1.02)
  • 5 years: 0.89 (0.81-0.96)
  • 8 years: 0.77 (0.62-0.95)

The authors point out numerous differences between their study population and the AFFIRM study population, including the fact that their subjects were older, were more likely to be female and to have CHF, and were more likely to receive beta-blockers in the rate control group. Acknowledging the limitations of observational studies, they write that “the long-term benefits of rhythm control drugs in AF found in this study need to be assessed in future studies.”

In an accompanying editorial, Thomas Dewland and Gregory Marcus write that the results of the observational study are “provocative” but “insufficient to recommend a universal rhythm control strategy for all patients with AF.” They remind their readers, however, “that no clinical trial has definitively shown that maintenance of sinus rhythm is inferior to rate control, and expert consensus recommends a rhythm control strategy for individuals with arrhythmia-attributable symptoms.”
Click here to read the press release from Archives…