FDA says cancer risk of Vytorin and Zetia is “unlikely” 1

The FDA “believes it is unlikely that Vytorin or Zetia increase the risk of cancer or cancer-related death.” The FDA statement is a follow-up to its August 2008 early communication about a safety review of the drugs following cancer concerns initially raised by the SEAS trial in August 2008. Despite the reassurance the FDA said it was unable to definitively rule out an association “at this time.”
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Lancet: Huge metaanalysis finds no causative role for CRP Reply

CRP is a strong and consistent marker for CV disease and other non-vascular diseases, like cancer and lung disease, but does not appear to be a cause of disease, according to a new meta-analysis in the Lancet. The new study is the largest effort yet to to sort out the controversial role of CRP. The study, by John Danesh and colleagues in the Emerging Risk Factors Collaboration (ERFC), combined information from 54 studies including 160,000 people in 18 countries. “The relevance of CRP to such a range of disorders is unclear,” the authors write. “Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.”
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Niacin helps restore protective effects of HDL in diabetics 1

HDL in diabetics is less protective than HDL in nondiabetics, but niacin can help restore some of its protective effects, according to a new study appearing in Circulation.

Investigators from Switzerland and Germany studied HDL from 10 healthy subjects and 33 patients with type 2 diabetes. Sajoscha Sorrentino and colleagues found that HDL from the healthy subjects, but not from the diabetics, stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell–mediated endothelial repair, suggesting, “markedly impaired endothelial-protective properties of HDL.”
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Primary PCI without surgical backup deemed safe in NYS study Reply

STEMI patients who receive primary PCI in hospitals without surgical backup have no significant differences in rates of death and the need for emergency surgery as similar patients treated at hospitals with surgical backup, according to a new study from the New York State PCI registry appearing in Circulation: Cardiovascular Interventions. However, patients at the PCI-only hospitals had higher rates of repeat target  vessel PCI, and patients who did not receive PCI had higher mortality rates.
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AHA: CV disease will cost $500 billion in 2010 Reply

The combined direct and indirect costs of cardiovascular disease in the US in 2010 will be half a trillion dollars, according to the AHA, which has just released its Heart Disease and Stroke Statistics – 2010 Update.

Here are some other key statistics:

In 2006 the overall death rate from CVD was 262.5 per 100 000:

  • white males: 306.6 per 100 000
  • black males: 422.8 per 100 000
  • white females: 215.5 per 100 000
  • black females: 298.2 per 100 000

CVD deaths declines from 1996 to 2006 by 29.2%, but in 2006 still accounted for more than one-third (34.3%) of all deaths in the United States (831,272 out of 2,426,264).
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TCFA: “the most relevant form of human disease in the history of mankind” Reply

It’s usually not stated quite so clearly. In an editorial in Circulation: Interventions Mt Sinai’s Pedro Moreno writes:

“…our field continues to struggle with the concept that percutaneous intervention may not prevent myocardial infarction or death in the stable patient. The main reason behind this controversial but rather accepted statement is that life-threatening coronary events arise most frequently from lesions that escape proper diagnosis and treatment. As a result, our efforts in clinical practice are almost totally consumed by the treatment of lesions that have limited impact on the natural history of atherothrombosis and CAD. Thus, it is imperative to reflect on this paradox, and do something about it.”

Moreno’s editorial is prompted by an interesting but not terribly surprising study by Steven Marso’s group at the Mid America Heart Institute that used IVUS to show that the longer someone has diabetes the more likely they are to have coronary plaque classified as TCFA (thin-cap fibroatheroma). TCFA, of course, is the type of plaque closely tied to plaque rupture and acute events. As Moreno writes:
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Review finds “no consistent or reproducible treatment effect” for serial calcium scans 2

There is no evidence to support annual coronary artery calcium (CAC) screening to measure atherosclerosis progression, according to a systematic review in Archives of Internal Medicine by Peter McCullough and Kavitha Chinnaiyan. Further, an accompanying editorial by Patrick O’Malley argues that “the answer to the problem of rescanning in the community… is to stop the current practice of initial screening first.”
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Are CT scans the wild west of today’s medicine? Reply

Are CT scans the wild west of today’s medicine, with little sense of law or regulation and a heightened expectation of premature death? Two new studies appearing in the Archives of Internal Medicine suggest the analogy might not be entirely inappropriate. More than 70 million CT scans are performed each year, representing a tripling of usage since 1993, yet there is little standardization in utilization patterns or radiation doses, and the consequence may be a much higher rate than expected of cancer and death in the coming decades.

“15,000 persons may die as a direct result of CT scans physicians had ordered in 2007 alone,” writes Rita Redberg, in an accompanying editorial.

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Wired: David Eddy’s efforts to replace human trials with computer models 1

We’re a little behind in our reading so we didn’t notice until now a fascinating feature article by Jennifer Kahn in the December Wired that’s likely to be of significant interest to many CardioBrief readers. The article provides an in-depth look at the efforts of David Eddy to develop highly sophisticated computer models to diminish the need for human clinical trials. Eddy is a polymath who had originally planned to be a  cardiovascular surgeon and was training at Stanford before deciding to restart his career. For the last 30 years he’s held a wide variety of jobs, including a long-term postion as Chief Scientist of the Blue Cross Blue Shield Association/Kaiser Permanente Technology Evaluation and Coverage (TEC) Program.

As often happens in Wired articles, the first half of the article is guilty of untempered enthusiasm for new technology, and naive readers might think that clinical trials with actual human subjects are about to go on the endangered species list, but the second half of the article adds some much-needed balance and perspective, and the final product offers a provocative insight into Eddy’s quixotic efforts to replace or augment in vivo studies with in silico studies.

Kahn starts her article with the story of Eddy’s efforts in 2004 to use Archimedes, his computer model, to replicate the Collaborative Atorvastatin Diabetes Study (CARDS) months before the results of the study became known. Here is Kahn’s description of what happened:
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Many dialysis patients undergoing PCI receive contraindicated antithrombotics Reply

More than a fifth of dialysis patients undergoing PCI receive the antithrombotic drugs enoxaparin and/or eptifibatide, which are cleared renally. These drugs are contraindicated in this population, and their use is associated with a significantly increased risk of major bleeding and death, according to a new report appearing in JAMA.
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New MRI technique shows– finally– that men and women have different hearts Reply

It won’t solve the age-old questions about the deeper differences between men and women, but  a new MRI imaging technique is revealing fundamental differences between the movement of men’s hearts and women’s hearts. The technique also found movement differences between young and old hearts. Ultimately, the new technique might aid in the earlier diagnosis of heart disease, say the authors.
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Rivaroxaban: EINSTEIN at ASH and another rock on the road to approval 1

The presentation of the EINSTEIN-Extension trial of rivaroxaban for VTE at the American Society of Hematology meeting in New Orleans on Tuesday was overshadowed by the drug’s developer’s disclosure of a new rock on rivaroxaban’s road to FDA approval.

The company developing rivaroxaban, Bayer, said in a press release that it would not respond to an FDA Complete Response Letter this year, as it had previously stated, but would instead “communicate an updated filing strategy in its Annual Press Conference on February 28, 2010,” according to a Bayer press release.
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RE-COVER at ASH: Dabigatran equals warfarin for VTE treatment Reply

Dabigatran (Pradaxa) is as effective as warfarin for the treatment of VTE, according to results of the RE-COVER study presented today at the American Society of Hematology meeting today and published online in the New England Journal of Medicine.

Sam Schulman and colleagues randomized 2539 patients with acute VTE to warfarin or dabigatran (150 mg twice daily) for 6 months. Patients were initially treated with heparin for 5 to 11 days. At 6 months the incidence of recurrent VTE was 2.2% (27 patients) in the warfarin group versus 2.4% (30 patients) in the dabigatran group, a difference which fell within the prespecified margin for noninferiority (p<0.0001). Major bleeding occurred in 20 dabigatran-treated patients and 24 warfarin-treated patients. There were no significant differences in mortality, ACS, or liver function test abnormalities.


Industry, academic researchers, and clinical trials: the slippery slope Reply

Ed Silverman’s venerable Pharmalot blog recently posted a useful summary of some of the conflict of interest problems that come up when physicians enroll their patients in clinical trials. The basis for the article was a 62-page paper from the  Center for Health & Pharmaceutical Law & Policy at the Seton Hall Law School.

But what really caught our eye was a detailed comment at the bottom of the post by “Pharmavet,” who is, apparently, a pharmaceutical executive with extensive experience in the clinical trials arena. You should read his entire comment, filled with insights gained from years of daily battle in the trenches, but here are a few highlights:
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BMJ: risk of VTE after surgery is higher and lasts longer than expected Reply

The risk of VTE after surgery is higher and lasts longer than expected, according to an article in the BMJ by Valerie Beral and colleagues on behalf of the Million Women Study collaborators. Using data from nearly 1 million women admitted to the hospital in the UK and nearly a quarter of a million admissions for surgery, the study found that women who had surgery were 70 times more likely to have VTE than women not having surgery. For outpatient procedures the risk was increased 10 times.
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BMJ: Large observational study finds excess CV risk with sulphonylureas, but benign outcomes with TZDs Reply

In recent years the debate over the proper use  and relative benefits of diabetes drugs has been unceasing. The significance of the controversy has been elevated due to the rising tide of diabetes and the commercial importance of many of these drugs. Now a new and very large observational study from the UK may help shed light on the real world impact of these drugs, but the more difficult decisions relating to these drugs surely will not be settled by studies of this nature.
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