Topol vs Gurbel: experts split on routine genotyping for DAPT 3

Routine genotyping to guide dual-antiplatelet therapy (DAPT) seems like a great idea. After all, argue Damani and Topol in a Viewpoint in JACC, the arguments are overwhelming, and the consequences of not rushing to adopt the new technique are dire.

They write that loss-of-function and gain-of-function variants of CYP2c19 are extremely common, and are “the root cause of adverse cardiovascular events during clopidogrel treatment.” Further, even though prasugrel and ticagrelor appear to be superior to clopidogrel, the benefit was likely caused by patients who were taking clopidogrel “who harbored resistance alleles.”

They continue: “Many experts will continue to call for results from randomized prospective trials before individualizing antiplatelet therapy on the basis of CYP2C19 carrier status, despite the overwhelming evidence presented here. This doggedness represents a false premise for a number of reasons and denies current patients state-of-the-art care. …we cannot afford to wait years for results from these trials that to date have yet to be initiated. In the interim, we should implement all potential interventions to help prevent the catastrophic outcomes of stent thrombosis and death in the tens of thousands of patients currently at risk.”
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Gust Bardy Answers Questions About the Entirely Subcutaneous ICD 1

Editor’s note: This item, in a slightly altered form, is republished with permission from CardioExchange, a new website for cardiovascular healthcare professionals from the New England Journal of Medicine. CardioBrief readers who are healthcare professionals are invited to register at the site.

Earlier today, at the annual meeting of the Heart Rhythm Society in Denver, Dr Gust Bardy presented the initial experience with a promising new device, an entirely subcutaneous ICD. The paper was published simultaneously online in the New England Journal of Medicine. Dr Bardy graciously agreed to answer questions about the device from the editors of CardioExchange.
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Lancet meta-analysis finds some benefits for fibrates Reply

A new meta-analysis has found evidence that fibrates may have a small beneficial effect on cardiovascular outcomes. The paper by Min Jun and colleagues is published online in the Lancet.

Combining data from 18 clinical trials including over 45,000 subjects, the investigators found that fibrates resulted in a 10% relative risk reduction for major cardiovascular events and a 13% reduction for coronary events. Fibrates had no effect on stroke, cardiovascular mortality, or sudden death.
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Medtronic tells physicians about rare software issue with its ICDs 1

Medtronic has informed physicians about a rare software issue with its ICDs.  News of the problem was first reported by the Hong Kong Department of Health and picked up by electrophysiologist and blogger Westby Fisher.

Medtronic said that it had received 5 reports of the problem out of approximately 144,000 devices implanted worldwide. According to Medtronic, a software update will be made available soon to correct the problem, which occurs in the Consulta CRT-D, Secura DR/VR, Concerto II CRT-D, Virtuoso II DR/VR, Maximo II CRT-D, and Maximo II DR/VR models. No injuries or deaths have been caused by the problem, the company said.
Click here to read Medtronic’s letter to physicians…

Vioxx, Avandia, Vytorin: absolute risk versus relative risk 3

There’s a fascinating discussion about Vioxx echoing around the blogosphere. (William Heisel has a nice summary here.) A few weeks ago Catherine DeAngelis, the editor of JAMA, spoke at the recent meeting of the Association of Health Care Journalists and said:

I believe Vioxx should not have been taken off the market. At least a million people, if told the truth about its side effects, would accept it because their lives could be lived with a lot less pain. There are a lot of people now whose lives are miserable because they have to live with arthritic pain.

At the same meeting, the editor of Reuters Health, Ivan Oransky, was critical of the way the Vioxx issue was reported by many journalists: “There was a doubling of heart attack risk, but the doubling was from a 1% risk to a 2% risk. If you lay that all out to readers, they can make much better decisions.”

I think DeAngelis and Oransky make valid points, but I think they miss a much more important point.
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Hong Kong authorities issue warning about Medtronic ICDs Reply

As far as I can tell, electrophysiologist and blogger Westby Fisher is the first person in the western hemisphere to publicly report a new, potentially life-threatening software problem with Medtronic ICDs. Fisher found a warning issued by the Hong Kong Department of Health.

As of April 19, Medtronic said it had received five confirmed reports of defects out of 144,000 devices sold worldwide. To date no patient injuries or deaths have been reported. The Hong Kong Department of Health said the software problems were “potentially life-threatening” but did not provide any details.
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The wealth gap: are cardiologists’ high salaries standing in the way of primary care? 1

High salaries for cardiologists and other specialists lead to an overwhelming lifetime advantage in wealth accumulation, according to a new study appearing in Health Affairs. That advantage may play a decisive role in the choice of medical careers, say Kevin Schulman and his colleagues in their article, “Can We Close The Income And Wealth Gap Between Specialists And Primary Care Physicians?”

The Duke researchers compared specialists, represented by cardiologists (who have the 14th highest median practice income among 68 medical specialties), to primary care physicians, represented by general internists and family physicians, as well as other non-physicians. Here is their estimated value of career wealth from college graduation until age 65:
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EHJ editors rebuffed GSK efforts to suppress Nissen editorial on rosiglitazone 4

The editors of the European Heart Journal rejected a request by a senior GSK executive to suppress an editorial written by Steve Nissen about rosiglitazone (Avandia).

The incident is recounted in a separate editorial written by the EHJ editor-in-chief, Thomas Lüscher, and two deputy editors, Ulf Landmesser, and Frank Ruschitzka, and published online on April 23. According to the editors, the EHJ received a letter (click here to download a PDF of the letter) on February 21, 2010 from the chairman of R&D at GSK, Moncef Slaoui. In response to the online publication on February 12 of an editorial by Nissen, the GSK executive “urged the journal not to publish the online editorial in print,” according to the EHJ editors. The EHJ editors recount their response: “The journal’s editorial board discussed the issue and unanimously agreed that such a demand was unacceptable.”
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The survey says: uphill battle for Effient, Plavix remains strong, anticipation grows for Brillinta 1

Sales of prasugrel (Effient) are slowly growing, but the road to blockbuster status appears blocked by continued strong current usage of clopidogrel (Plavix) and, in the future, widespread anticipation and excitement over ticagrelor (Brillinta). In its last financial statement Lilly reported worldwide sales of Effient of $8.8 million in the first quarter, $4.5 million in the US. (Plavix sales in 2010 are estimated at $6.5 billion.)

Leerink Swann, a financial research firm, released the results of a survey of 106 US cardiologists that provides insight into the antiplatelet market. The survey found that physicians remain comfortable using clopidogrel and rate it as the “safest drug with good efficacy,” though “drug interactions and non-responders [are] becoming clinically relevant.”
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TMI or the future of medicine? Complete human genome used in patient assessment Reply

Three extraordinary papers in the Lancet provide a fascinating first glimpse at issues that will be the topic of discussion and debate for the next generation at least. For the first time, investigators at Stanford and Massachusetts General Hospital used a complete human genome of an individual patient to provide a clinical assessment of the patient, a 40-year-old asymptomatic man with a family history of coronary artery disease and sudden death.

The  analysis of  2.6 million SNPs and 752 copy number variations found that the patient was at increased risk for MI, type 2 diabetes, and some cancers, the researchers reported. They also found three rare variants of genes that have been linked to sudden cardiac death. They also found an LPA variant associated with familial CAD and mutations linked to clopidogrel resistance and a positive response to lipid-lowering therapy. These were some of the more clinically relevant findings, but an important aspect of the Lancet report is the nearly overwhelming amount of information that can be obtained from the whole-genome approach.
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Roche announces more positive results for taspoglutide Reply

Once again Roche has announced positive phase III results for taspoglutide, a once-weekly GLP-1 analog under development. The drug is being tested in a series of phase 3 studies that compose the T-emerge clinical trial program.

In today’s announcement, Roche said the T-emerge 3 study showed that taspoglutide was superior to placebo for the primary endpoint of change in HbA1c when used in addition to metformin and pioglitazone in 326 patients randomized to taspoglutide 10 mg once weekly, taspoglutide 20 mg once weekly, and placebo. As in previous studies, Roche said the drug “was generally well tolerated and the most frequently reported adverse events among taspoglutide treated patients were nausea and vomiting.”
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Vitamin B and steroids: monuments to human folly 4

Walk into any Vitamin Shoppe or GNC and you can see them: people looking to fight a cold, reduce “stress”, sleep better, or build bigger muscles. They’re all looking for a quick fix with no downside. They’re all deluded.

Two new clinical trials testing the effects of vitamin B and steroids serve to demonstrate the folly of human hopes for quick fixes that seem harmless. But they also demonstrate the only antidote to such folly: the objective and critical assessment of those hopes.
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US Judge rejects $296 million plea agreement for Guidant Reply

A US federal judge rejected a proposed $296 million plea agreement which would have allowed Guidant to settle the investigation into the company’s handling of defective ICDs. As reported here last week, cardiologists Barry Maron and Robert Hauser, who originally brought the case to public attention, wrote a letter to the judge urging him to reject the proposed settlement.

In the 37-page opinion, Judge Donovan W. Frank said that the Justice Department had not held Guidant (now owned by Boston Scientific) “sufficiently accountable” for its actions, according to a New York Times story by Barry Meier. The Times also said that the judge had “disagreed with the Justice Department’s decision not to seek corporate probation for Guidant and its current parent company, Boston Scientific.”
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Calcium screening: another positive study, another critical editorial Reply

Once again a study has turned up results that appear to favor widespread application of calcium screening. And once again an editorial has pointed out that the technique is still not ready for prime time. (And we predict that once again the proponents of calcium scans will trumpet the study as absolute justification for widespread adoption of calcium screening.)

This time, in a study appearing in JAMA, Polonsky et al used data from 6,000 patients enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) to assess the value of adding coronary artery calcium (CAC) scores to a traditional risk factor. By adding CAC scores to traditional risk factor assessment, nearly a quarter of subjects who experienced a CHD event during a median 5.8 years of followup were reclassified as high risk, while 13% who had no events were reclassified as low risk.
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PPIs and Clopidogrel: new study finds evidence that pantoprazole may also be a problem Reply

Over the past few years physicians have grown increasingly concerned about possible negative consequences when clopidogrel is given to people taking PPIs. Last November the FDA added a warning to the clopidogrel label and issued a public health advisory on the interaction between clopidogrel and omeprazole. Now a new study lends fresh support to concerns, and provides the first substantial evidence that another PPI, pantoprazole, may also be a problem.

Researchers at Prescription Solutions and the University of Washington reviewed data from patients enrolled in a multistate private and Medicare insurance plan who were taking clopidogrel and a PPI and compared them with matched patients (using propensity scoring) with patients taking clopidogrel alone. In their report in Archives of Internal Medicine, Karen Stockl and colleagues found that when compared to patients on clopidogrel alone, patients also taking a PPI had a 93% higher risk of rehospitalization for MI (adjusted HR = 1.93, CI 1.05–3.54, p=0.03) and a 64% higher risk of rehospitalization for MI or stent implantation (adjusted HR = 1.64, CI 1.16–2.32, p=0.05).
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Guest Post: Medical Societies’ New Ethics Code: Secret Q&A Document Revealed Reply

Editor’s Note: A transforming moment in the current discussion about conflict of interest in medicine occurred on November 25, 2007, when the New York Times Magazine published a lengthy article by Dr. Daniel Carlat, a psychiatrist affiliated with Tufts University. In the article, Carlat wrote at length about his experience as a paid speaker to other physicians and his eventual decision to quit giving such talks. Although the details of Carlat’s story could hardly have been a surprise to most physicians or other observers of contemporary medical culture, the fact is that this kind of discussion had never before occurred in public. And once the cat had been let out of the bag there was no putting it back in. Dr. Carlat now writes a blog, The Carlat Psychiatry Blog, which has become one of the most intelligent and reliable sources for information and analysis about COI issues. Dr. Carlat graciously agreed to allow CardioBrief to reprint the following item, which provides a brilliant and humorous perspective on yesterday’s announcement by the Council of Medical Specialty Societies of a new Code for Interactions with Companies.

Medical Societies’ New Ethics Code: Secret Q&A Document Revealed

by Dr. Daniel Carlat

The Council of Medical Specialty Societies just announced a new Code for Interactions with Companies. They have received good press so far. According to AP, “It’s the most sweeping move ever taken by the Council of Medical Specialty Societies to curb conflict of interest…”

But The Carlat Psychiatry Blog has just obtained a disturbing highly classified Q&A document leaked by a mole within the Council. Or maybe we just made the thing up. Read the following excerpt, and you can decide.
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Guest Post: the long afterlife of Joshua Oukrop 1

Editor’s Note: In response to a plea agreement in which Boston Scientific would pay $296 million to resolve the well-known case involving defective Guidant ICDs that the company failed to disclose, the New York Times and the Minneapolis Star Tribune report that the two cardiologists who first brought the issue to public attention have sent a letter to the judge in the case asking him to reject the proposed settlement. In the following guest post, Westby G. Fisher, an Illinois electrophysiologist and author of the popular Dr Wes blog (where this post was originally published), raises the interesting question: what role should physicians play in deciding damges? More importantly, Fisher discusses the important changes brought about by the case.

When Doctors Decide Damages

by Westby G. Fisher

In an interesting twist to the ongoing saga of device recalls, the Minneapolis StarTribune reported that the two doctors, Robert Hauser, MD and Barry Maron, MD who first brought the Prism II ICD device malfunction to public attention by releasing their story to the New York Times in 2005, wrote a letter to the judge reviewing the plea bargain agreement and told him:

We are physicians who cared for Joshua Okrup (eds note: should be “Oukrop”), a 21 year-old college student, who died when his Guidant Prizm 2 implantable cardioverter-defibrillator (ICD) short-circuited and failed to deliver a life-saving shock. His unnecessary death was caused by a product defect that Guidant Inc. had known about for years and failed to inform patients, physicians, and the U.S. Food and Drug Administration. Accordingly, we are extremely dismayed by the U.S. Attorney General’s decision to enter into a plea agreement with Guidant LLC, rather than prosecute the company and the individuals responsible for this egregious act. On behalf of the patients who died or suffered pain and mental anguish as the direct result of Guidant’s illegal and unethical behavior, we urge you not to accept the plea agreement.

An out-of-court $296 million plea agreement is not enough it seems.
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IOM report heralds new FDA initiative to gradually cut salt in processed foods Reply

Update: In response to the Washington Post article discussed below, the FDA issued a statement saying the article “leaves a mistaken impression that the FDA has begun the process of regulating the amount of sodium in foods. The FDA is not currently working on regulations nor have they made a decision to regulate sodium content in foods at this time.”

On the heels of today’s release of an Institute of Medicine report, “Strategies to Reduce Sodium Intake in the United States,” the FDA will announce tomorrow a major initiative that would gradually reduce the amount of salt added to processed foods. The FDA initiative was reported by Lyndsey Layton in the Washington Post.
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Small steps lead to big reduction in risk for overweight Mayo Clinic cardiologist Reply

Moderate changes in lifestyle can lead to big reductions in risk, as reported in a feature story in the Wall Street Journal by Ron Winslow. The story opens with an anecdote from Mayo Clinic cardiologist Stephen Kopecky, who describes the case of a 240 pound, 49-year-old  man with a scary lipid profile. “He may not have been a heart attack waiting to happen, but that was the direction he was headed,” writes Winslow.

The man then started to exercise regularly and to eat a healthy diet, resulting in an 18 pound weight loss and a dramatic improvement in his lipids. Winslow quotes Kopecky, who points out that the case shows “that we can all help ourselves tremendously taking small steps and doing something that’s achievable.”

But it’s not until the very end of the story that Winslow pulls the rabbit out of the hat:
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Residual Risk Reduction Initiative: promotion or education? Reply

Cardiologists and other physicians have reported receiving an email lately from an organization called the Residual Risk Reduction Initiative. Here’s how the organization describes itself:

The Residual Risk Reduction initiative (R3i) is a worldwide, academic, multidisciplinary, non-profit, Swiss-law Foundation established by international researchers and clinicians who recognize the importance of the high risk of fatal and non-fatal macro- and micro-vascular complications occurring in patients with atherogenic dyslipidemia who are already receiving the current standards of care.

It sounds like a worthy program. Who could be against efforts to further reduce cardiovascular risk? Unfortunately, R3i, in reality, is something more (or less) than an altruistic organization: it’s a keystone in the promotional efforts of Abbott to sell more of its fenofibrate drugs (TriCor and TriLipix) and to “spin” the negative ACCORD trial into a positive message for fenofibrate. ACCORD, you will recall, was a negative trial that failed to demonstrate the benefits of fibrates in type 2 diabetics already taking statins, although there was a possible benefit in the subgroup of patients who had both high baseline triglycerides and low HDL cholesterol (interaction p=0.057).
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Boston Scientific resumes sales of Cognis and Teligen ICDs Reply

Boston Scientific announced today that it had received approval from the FDA to resume sales of most of its ICDs and CRT-Ds following a 30 day suspension. Sales of Cognis CRT-Ds and Teligen ICDs will resume immediately. The company said it had “found a few additional instances where the Company did not submit the appropriate documentation for validated manufacturing changes” in its older devices, and these will remain off the market until the company receives FDA approval to resume their sales. (You can read previous coverage on CardioBrief of this story here, here, and here.)
Click here to read the Boston Scientific press release…

Even more questions about Multaq and Prystowsky, alas 1

I’m feeling a bit like Al Pacino in Godfather III: every time I think I’m out of the Multaq story I get pulled back in.

A sharp observer forwarded an article posted online in the Journal of Cardiovascular Electrophysiology: “The Impact of New and Emerging Clinical Data on Treatment Strategies for Atrial Fibrillation.” First author: Eric Prystowsky.

The simple truth is that the entire article was developed and paid for by Sanofi. The reason is very simple: Under the pretense of a comprehensive review of new data on AF, the article recommends that dronedarone (Multaq) be considered as a first line agent for all but one indication for AF across the entire cardiovascular spectrum. (This appears to be identical to Prystowsky’s position in the lecture on the ACC/HRS website.)

Here are a few further details and observations:
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Final results of ARBITER 6-HALTS confirm CIMT benefit with niacin and no benefit with ezetimibe Reply

Last November the initial presentation at the AHA and simultaneous publication in the New England Journal of Medicine of the ARBITER 6-HALTS trial resulted in a storm of confusion and controversy. Now the final results of the trial have been published in the Journal of the American College of Cardiology. The data appear to provide strong confirmation that niacin was effective in inducing atherosclerosis regression as measured by CIMT while ezetimibe had no such effect.
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Promising early results for “valve-in-valve” approach to failing bioprosthetic valves 1

Fixing a failing porcine or bovine heart valve with the percutaneous implantation of a mechanical valve inside the previous valve appears promising, according to a new report by  John Webb and colleagues in Circulation. But an accompanying editorial warns that the new technology needs to be carefully assimilated.

“Generally the transcatheter valves work very well for treating leaky, failed surgical valves,” said Webb, in an AHA press release. “The procedure only works well if the original surgical valve is large enough for the new transcatheter valve to fit inside it. Most surgical valves are large enough, but not all. If the surgical valve is small, the new valve may open more fully than the old valve but not as well as you would like.”
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