Biomarkers: Don’t Believe the Hype Reply

Watch out for hype when examining the biomarker literature, a new study published in JAMA suggests. John Ioannidis and Orestis Panagiotou first searched the literature  and identified  highly cited studies of biomarkers that included a relative risk calculation of effect size on a particular outcome. Most of the 35 studies reported cancer- or cardiovascular-related outcomes. They then performed a second search to find subsequent meta-analyses on the same biomarker and outcome.

The investigators then compared the effect size of the first study with the subsequent studies. For 30 of the 35 studies, the effect size reported in the largest study included in the meta-analysis was smaller than the effect size reported in the original highly cited study. In a comparison of the original study with the entire meta-analysis, the same pattern was observed, with 29 of the 35 meta-analyses reporting a smaller effect size.
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Comment: Abbott & Costello Weigh In On Niacin 1

Editor’s note: Here’s a great comment from a reader on the previous post about the NLA and AIM-HIGH:

I am a patient and policy prof who turned down niaspan because there was no scientific evidence of benefit relative to risk, which is not trivial.

There still isn’t, unless having more sexy numbers is considered a benefit.

The original Abbott was more clear about it: “‘I don’t know’s’ on third.”

Now we know more than we did, but apparently that is supposed not to affect how we play ball.

Someone explain to me why this isn’t crazy.

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National Lipid Association: AIM-HIGH Results “Disappointing” But Prescribing Practices Should Not Change 1

The National Lipid Association has issued a statement to its members about the AIM-HIGH Study. The NLA acknowledges that the “findings are disappointing since clinicians have used extended-release niacin to treat patients with low HDL-C” but urges its members to “await full availability and review of the trial before integrating this information into clinical practice.”

The statement recommends that

physicians should not alter their prescribing practices at this time if that would deter patients from achieving NCEP targets. A continued focus on achieving risk stratified NCEP goals and recommending diet changes and especially exercise regimens is warranted for managing cardiovascular disease in patients with known risk and low HDL levels.
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NHLBI Stops the AIM-HIGH Trial of Niacin 1

(Updated with comments from William Boden, Sanjay Kaul, James Stein, Monty Krieger, and Allen Taylor)– The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health) trial of niacin has been stopped early by the NHLBI. The trial was designed to test the addition of high dose, extended-release niacin (Niaspan) to statins in people at risk for CV events who had well-controlled LDL but low HDL and elevated triglyceride levels.

The trial was stopped early after a regularly scheduled meeting on April 25, 2011 of the  data and safety monitoring board (DSMB) determined that there was no difference in the rate of clinical events between the two treatment groups. As expected, niacin was effective at raising HDL and lowering triglyceride levels, but it had no effect on the composite endpoint of fatal or nonfatal MI, strokes, hospitalizations for ACS, or the rate of revascularization procedures.
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Senate Report Uncovers Sanofi Attempts to Stifle Generic Lovenox Reply

A report issued by the US Senate today contains numerous documents demonstrating attempts by Sanofi to orchestrate a negative perspective on generic Lovenox by the FDA. The documents outline Sanofi’s relationships with the North American Thrombosis Forum (NATF), the Society of Hospital Medicine (SHM), and a Duke University pulmonologist, Dr. Victor Tapson.

A Sanofi slide presentation shows that the company

sought to encourage ‘independent interaction with regulatory authorities.’’ Specifically, the ‘‘Progress To Date’’ slide identifies the ‘‘Independent communication with FDA by professional organizations and prominent [key opinion leaders]’’ regarding Lovenox.

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FDA Approves Xience Nano for Small Vessels Reply

The FDA has approved the Xience Nano everolimus-eluting stent, Abbott has announced. The stent is based on the same platform as the popular Xience V stent, and can be used in vessels as small as 2.25 mm. The approval was based on results from the SPIRIT Small Vessel clinical trial. The rate of target lesion failure was 8.1% in that trial, similar to the rate observed in the SPIRIT trials with XIENCE V.
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New Onset AF Linked To Increase in Death and CV Events Reply

In the Women’s Health Study, which followed nearly 35,000 women for more than 15 years, mortality was significantly higher in the 1011 women who developed AF than in the women who did not, according to a report by David Conen and colleagues published in JAMA.

Here is the incidence rate (per 1000 person-years of followup) for women who developed AF compared to women without AF:
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Copeptin May Help Predict CV Death in Elderly HF Patients Reply

The biomarker copeptin, which is a surrogate marker of vasopressin, may help predict the risk of death in elderly HF patients, according to a new study in JAMA. Urban Alehagen and colleagues followed 470 elderly HF patients from 1996 through 2009, during which time there were 226 deaths from any cause and 146 deaths from cardiovascular causes. They found that copeptin was both an independent predictor of death and also contributed additional prognostic information when used in tandem with the established biomarker NT-proBNP.
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What Is the Impact of Screening Low Risk Patients with CT Angiography? Reply

In a study published online in Archives of Internal Medicine, John McEvoy and colleagues examine the impact of screening low risk patients with coronary CT angiography (CTA). They compared 1000 South Korean patients who underwent CTA and compared them to 1000 matched controls.

CTA identified 215 people with coronary atherosclerosis. At 90 days and at 18 months, statins and aspirin were being taken by a significantly higher percentage of patients in the CTA+ group than in the CTA- group or in the matched control group:
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Eplerenone Found To Also Reduce AF in HF Patients Reply

Results from EMPHASIS-HF (Eplerenone and Atrial Fibrillation in Patients with Systolic Heart Failure and Mild Symptoms) previously showed that adding the aldosterone antagonist eplerenone to standard therapy in patients with NYHA class II heart failure resulted in the reduction of the composite endpoint of death from cardiovascular causes or hospitalization for heart failure. Now, a sub-analysis of the trial presented by Karl Swedberg at the Heart Failure Congress 2011 in Gothenburg, Sweden suggests that eplereone may have the additional beneficial effect of preventing atrial fibrillation (AF) in heart failure patients.
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Annuloplasty Rings, Edwards, and the FDA: More Details Emerge Reply

The routine approval of implanted medical devices via the 510(k) premarket notification process, and in particular the controversy over Edwards’ Myxo Etlogix annuloplasty ring, get new scrutiny in an article in the Chicago Tribune by Jason Grotto and Deborah Shelton.

The Myxo controversy began in 2008 when a patient who received the device had a poor outcome after receiving the Myxo Etlogix device and discovered that the device had not undergone FDA review because, Edwards claimed,  only a pro forma notification to the FDA was required under the 510(k) process. The patient also complained that her surgeon, Patrick McCarthy of Northwestern Memorial Hospital, had not informed her that he had invented the device. (See heartwire for extensive previous coverage of the controversy.)

The Tribune article adds two important new details to the story:
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FDA Panel Delivers Mixed Verdict on Trilipix (Fenofibrate) Reply

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee delivered a mixed verdict on fenofibrate (Trilipix, Abbott). On the one hand, the panel agreed unanimously that the FDA should require Abbott to perform a large clinical trial in high risk patients with elevated triglyceride levels and low HDL levels who nevertheless have achieved target LDL cholesterol levels on statin therapy.
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ProPublica: Medical Schools Plug Holes in Conflict-of-Interest Policies Reply

Editor’s note: The following post is reprinted with permission from ProPublica. It is the latest installment in ProPublica’s Dollars for Doctors: How Industry Money Reaches Physicians, an ongoing investigation.

Medical Schools Plug Holes in Conflict-of-Interest Policies

by Charles Ornstein and Tracy Weber ProPublica, May 19, 2011, 1:01 p.m.

Stanford University has taken disciplinary action against five faculty members at its medical school after determining they violated school policy by giving paid promotional speeches for drug companies, a spokesman said.

The move followed a ProPublica investigation in December that found Stanford [1] and other teaching hospitals weren’t enforcing their own conflict-of-interest rules.

At Stanford, which has one of the nation’s toughest policies [2], ProPublica identified more than a dozen faculty members — including medical staff leaders — who were paid speakers.
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Part 3: The NLA Responds To Questions 5

Editor’s Note: This is the final installment of a three-part series on the National Lipid Association. The first part focused on the NLA’s publication of a series of papers offering expert guidance on familial hypercholesterolemia, and raised questions about the role of industry in the documents. The second part explored additional questions about the NLA’s relationships with industry and other issues concerning the organization’s management. In this installment, the NLA answers questions sent to them about some of the issues raised in this series. The following material is reprinted without editing from the NLA response.
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Part 2: The National Lipid Association And Industry 5

Editor’s Note: This is the second of a three-part series on the National Lipid Association. The first part focused on the NLA’s publication of a series of papers offering expert guidance on familial hypercholesterolemia, and raised questions about the role of industry in the documents. This second part explores additional questions about the NLA’s relationships with industry and other issues concerning the organization’s management. In the third part the NLA answers questions sent to them about some of the issues raised in this series.

Industry support for NLA runs well beyond the FH guidelines.  It is almost certainly not a coincidence that the attention newly focused on FH comes at the same time as several new drugs for FH are nearing regulatory approval.  Here’s the cover of a brochure recently published by the NLA:
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Part 1: The National Lipid Association and the FH Guidelines 6

Editor’s Note: This is the first of a three-part series on the National Lipid Association. This first part focuses on the NLA’s publication of a series of papers offering expert guidance on familial hypercholesterolemia (FH) and raises serious questions about the role of industry in the documents. The second part explores additional questions about the NLA’s relationships with industry and the management of the organization. In the third part the NLA answers questions sent to them about some of the issues raised in this series.

In conjunction with its annual meeting in New York City, the National Lipid Association (NLA) is publishing in its own Journal of Clinical Lipidology a series of clinical guidance papers authored by “expert panels” on the subject of familial hypercholesterolemia (FH). With the help of a public relations campaign, the NLA hopes to focus more attention than usual on this group of genetic lipid disorders.

Lipid experts– NLA supporters and critics alike– agree that FH is a serious disorder that can cause premature coronary artery disease and death in nearly everyone with the disease who is left untreated and that efforts should be increased to identify and treat more people with FH. But critics say that the NLA recommendations are misguided in at least one key point and, more significantly, the guidelines, and the NLA itself, are deeply tarnished by the NLA’s extensive connections with industry.
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The Curse of the Egyptian Mummy: Coronary Artery Disease? 3

Could the real curse of the mummy be coronary artery disease? Despite strict adherence to the original Mediterranean diet and a complete lack of tobacco, trans-fats, and refined sugars, an Egyptian princess who died around 1550 BC is the first person in history to receive a diagnosis of coronary artery disease.

A CT scan of the princess was presented today at the International Conference of Non-Invasive Cardiovascular Imaging in Amsterdam. The princess, who had blockages in her left and right coronary arteries,  was one of 52 Egyptian mummies included in the  study. 20 of the mummies had definite signs of atherosclerosis, but only 3 had evidence of coronary narrowing.
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ProPublica: Cardiac Society Draws Bulk of Funding From Stent Makers 1

Editor’s note: The following post is reprinted with permission from ProPublica. It is the latest installment in ProPublica’s Dollars for Doctors: How Industry Money Reaches Physicians, an ongoing investigation.


Cardiac Society Draws Bulk of Funding From Stent Makers

by Charles Ornstein, ProPublica, May 13, 2011, 1:27 p.m.

A Pittsburgh hospital informed 141 patients [1] earlier this year that they may have received unneeded angioplasties and stents [2], the tiny mesh tubes inserted to keep arteries open.

A Towson, Md., cardiologist faces a hearing on the fate of his medical license [3] after being accused of implanting stents unnecessarily in more than 500 patients.

And this week, a new study found [4] that more than half of patients with stable heart disease who received angioplasty and stents didn’t first receive medications, as scientific guidelines recommend.

While a host of lawsuits and research studies has raised questions about the overuse of stents, the group that represents cardiologists who implant them relies heavily on income from the makers of these devices.
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TAVI & Stroke: More Details Surface About PARTNER A Reply

In the past year transcatheter aortic valve implantation (TAVI) has emerged as a possible new treatment for  patients with aortic valve disease who are not surgical candidates (the PARTNER B study) and for some patients as a viable alternative to surgery (the PARTNER A study). A major lingering question about the PARTNER A study was the higher rate of stroke in the TAVI arm of the study, although overall TAVI was found to be noninferior to surgery in that trial. In a presentation (PowerPoint slide set) earlier this week at the annual meeting of the American Association for Thoracic Surgery, Craig Miller presented results of the PARTNER A stroke substudy.

Overall, said Miller, the 30 day rate of stroke and TIA was low in both groups, considering the very high baseline risk of the patients:
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Study Finds Little Effect of COURAGE On Adoption of Optimal Medical Therapy Reply

Optimal medical therapy (OMT) for patients with coronary artery disease (CAD) was not significantly boosted by the publication of the COURAGE trial, despite the clear message from that trial showing the benefits of OMT, according to a new study published in JAMA.

William Borden and colleagues used data from 467,211 patients in the National Cardiovascular Data Registry to analyze the use of OMT in CAD patients prior to PCI and at the time of discharge, both before and after COURAGE was published.
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Trial REVEALs No Benefit And Some Concerns With EPO After Primary PCI 1

Erythropoietin alfa failed to reduce infarct size and was associated with more cardiovascular events when given after successful PCI in STEMI patients, according to results of the REVEAL (Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction) trial published in JAMA.

In a study with a dose-escalation safety phase and a single dose efficacy phase, 222 patients at 28 sites in the US were randomized to epoetin alfa or placebo following successful reperfusion. Investigators found no difference in infarct size as assessed by MRI. Patients 70 years of age or older, a prespecified subgroup, had a significant increase in infarct size in the first week:
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