FDA Issues Warning Letter To CoreValve Investigator Reply

The FDA has issued a warning letter to an investigator in the Medtronic CoreValve US Pivotal Trial. The letter cites numerous serious violations relating to the treatment of subjects in the trial testing the experimental Medtronic TAVI (transcatheter aortic valve implantation) device. The violations were uncovered during an FDA inspection last summer.

The subject of the FDA warning is Michael Ring, one of the two principal investigators of the CoreValve trial at the Providence Sacred Heart Medical Center site in Spokane, WA.

Click here to read the full story on Forbes. (Updated to include an additional comment from Dr. Ring.)

English: A warning sign with an exclamation mark

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HPS2-THRIVE Coming Attraction: First Look At What Went Wrong With Niacin Reply

In a few weeks, on March 9, the main results of the HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) study will be presented in San Francisco at the annual meeting of the American College of Cardiology. These results have been eagerly awaited since Merck’s brief announcement in December that the trial had not met its primary endpoint and that it would no longer pursue approval of Tredaptive, the combination of extended-release niacin and laropiprant, in the US. The trial was designed to assess whether adding the niacin/laropiprant combination to standard statin therapy in high risk individuals would further reduce vascular events.

Now, serving almost as a coming attraction for the main event at the ACC, an important substudy from HPS2-THRIVE has been published in the European Heart JournalThe paper discusses the trial design, the pre-specified muscle and liver outcomes, and the reasons for stopping treatment during the trial.

Click here to read the full story in Forbes.

European Heart Journal

Mixed Results For Spironolactone In Heart Failure With Preserved Ejection Fraction Reply

Although the mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone (Inspra, Pfizer) have been shown to be beneficial in patients with heart failure (HF) with reduced ejection fraction (EF), their role in heart failure patients with preserved EF has not been tested until now. Now the results of the Aldo-DHF (Aldosterone Receptor Blockade in Diastolic Heart Failure), published in the Journal of the American Medical Association, demonstrate that although the treatment works as expected to improve diastolic function in this patient population, no clinical benefits were observed in association with these changes.

422 patients in Germany and Austria with NYHA class II or III heart failure with preserved LVEF were randomized to spironolactone or placebo for one year.  Compared with placebo, spironolactone was associated with improvements in LV end-diastolic filling, LV remodeling, and neurohumoral activation. However, there were no significant differences in maximal exercise capacity or quality of life between the groups.

Click here to read the full post on Forbes.

 

The Mediterranean Diet: The New Gold Standard? 1

Earlier today I summarized the important new PREDIMED study published in the New England Journal of Medicine showing the cardiovascular benefits of the Mediterranean diet. This study– a rare and much welcome instance of a large randomized controlled study of a diet powered to reach conclusions about important cardiovascular endpoints– has been widely praised and will undoubtedly have a major effect in the field of nutrition and will influence lots of people to adopt some form of a Mediterranean diet.

The study’s major potential weakness appears to be that the control group didn’t get a fair chance.

Dean Ornish, probably the best-known and most passionate advocate of low-fat diets, goes much further in attacking the credibility of the trial…

The really great thing about the Mediterranean diet, by contrast, is that we know with 100% certainty that it is possible for people to live and eat this way, since they’ve been doing so for millennia. It’s true, though, that the new study didn’t really demonstrate that the Mediterranean diet is better than a true low-fat diet. But it did demonstrate that a Mediterranean diet is healthier than what most people are currently eating. So it’s a good example of a real world trial.

…Now that the Spanish PREDIMED study has been published, I think it must be considered the gold standard. Now it is up to the AHA, and Ornish, to prove that their diets are better than, or even as good as, the Mediterranean diet.

Click here to read the complete story on Forbes.

olive oil and almonds copy

Large Trial Shows Cardiovascular Benefits Of Mediterranean Diet 3

A large new trial offers powerful evidence that the Mediterranean diet can reduce the risk of cardiovascular disease. Results of the PREDIMED (Prevención con Dieta Mediterránea) study were published online in the New England Journal of Medicine.

Spanish investigators randomized 7,447 people at high risk for cardiovascular disease to one of three groups: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or a control group in which people were advised to lower their intake of dietary fat. The diets were designed not to restrict calories but to change the composition of the diet.

The trial was stopped early in July 2011 by the data and safety monitoring board when the benefits in the Mediterranean diet groups crossed a predetermined boundary….

One PREDIMED investigator, Emilio Ros, told CardioBrief that he believes the results of the trial mean that current recommendations regarding dietary fat should be changed to reflect that a “high fat, high vegetable fat diet is optimal for cardiovascular health.” Another study investigator, Ramón Estruch, said that “a major problem with lowfat diets is their low potential for long-term sustainability.” He said that “the results clearly demonstrate “the superiority of the Mediterranean diets.”

Click here to read the full story on Forbes.

olive oil and almonds copy

Are Most People With Complex Coronary Disease Getting The Best Treatment? 1

angiogram

The relative value of PCI (stents) and bypass surgery for the treatment of people with blocked coronary arteries has been a topic of intense interest and debate for more than a generation now. Over time, the less invasive and more patient-friendly (and less scary) PCI has become the more popular procedure, but the surgeons (who perform bypass surgery) and cardiologists (who perform the less invasive PCI) have argued furiously about which procedure is safest and will deliver the most benefit in specific patient populations. In general, the most complex cases require the more thorough revascularization provided by surgery, while the more simple cases do well with PCI and can therefore avoid the trauma of surgery. But the specific criteria have remained murky, and interventional cardiologists have aggressively sought to take on increasingly more complex cases.

Now, long term results from a highly influential trial comparing the two procedures offer what is likely the most definitive solution we are likely to have for a very long time. Five year results from the SYNTAX trial have now been published in the Lancet.

Here’s some of the perspective on this study from two very savvy cardiologists, Rick Lange and L. David Hillis. (These comments are extracted from their original publication in CardioExchange. Note that I work on CardioExchange, which is published by the New England Journal of Medicine.)

…The “bottom line” conclusions are:

  1. CABG should remain the standard of care for patients with complex lesions…
  2. For patients with 3-vessel disease considered to be less complex… PCI is an acceptable alternative.
  3. All the data from patients with complex multivessel CAD should be reviewed and discussed by a cardiac surgeon and an interventional cardiologist, after which consensus on optimal treatment can be reached.

But Lange and Hillis, while they seem to largely agree with the study findings, also cast doubt on whether most physicians are likely to pay attention to the study details. They wonder whether most hospitals actually live up to the standards in the study, which requires, for each patient, a review of each patient by the multidisciplinary heart team, and the calculation of a complex SYNTAX score to establish the precise degree of risk.

Okay, let’s be honest….

  1. In your hospital, in what percentage of patients with left main or 3 vessel CAD are all the data systematically reviewed and discussed by a “Heart Team”?
  2. Do you calculate SYNTAX on all patients with left main or 3 vessel disease, or do you usually just “guestimate” lesion complexity?

If Lange and Hillis’s suspicions are correct, many people with complex coronary lesions are not receiving the best possible care. Hmmm.

Study Casts Doubt On Value Of Genetic Testing For Familial Hypercholesterolemia 3

new study published online in the Lancet suggests that one of the main screening plans that relies on genetic tests will fail to identify a substantial portion of people with familial hypercholesterolemia.

Investigators from the UK and Belgium analyzed DNA from several cohorts of FH and non-FH patients. Their chief finding was that a large percentage of FH patients did not have one of the single genetic mutations known to cause FH. Instead, these patients, termed “polygenic,” were found to have variants in multiple genes, each of which had a small LDL-raising effect, but when combined resulted in LDL levels similar to those in people with known FH mutations.

According to one cholesterol expert: 

The take home is that genetic screening is not a panacea and that screening based on fasting ipids makes most sense. Indeed, I never understood genetic screening for this disease anyway, since the phenotype (hypercholesterolemia) is what kills people, not the genotype, the phenotype is readily available with a blood test, the disease is not immediately fatal (It takes years to develop), and treatment is based on the numbers. It is like asking for a gene test fro sickle cell anemia. You can look at blood and make the diagnosis.

Click here to read the complete story on Forbes.

 

New Studies Examine Prolonged Anticoagulation For VTE Recurrence Reply

Three studies published in the New England Journal of Medicine provide important new information about the risks and benefits of extended prophylaxis using two of the new oral anticoagulants in patients who have had venous thromboembolism (VTE).

In an accompanying editorial, Jean Connors writes that “deciding how to balance the risks and benefits of extended anticoagulation is difficult” in patients with unprovoked VTE, since the risk of recurrent VTE may reach 40% at 5 years. Patients at low-to-moderate risk of recurrence may benefit from aspirin, which “may be safer than the newer agents,” though “it appears to have less efficacy in reducing recurrent events.” For patients at higher risk, “the new targeted anticoagulants are attractive alternatives to warfarin. The finding that a low prophylactic dose of apixaban has the same efficacy as the full therapeutic dose, with no increased risk of major bleeding, may tip the risk-to-benefit ratio in favor of extended treatment for this patient population. The wide therapeutic window of this agent enables use of a lower dose that retains great efficacy with no or only a minimal increase in bleeding.”

Click here to read the entire post in Forbes.

The New England Journal of Medicine

 

 

 

Small Study Explores Expanded Use For TAVI In Native Valve Aortic Regurgitation Reply

As transcatheter aortic valve implantation (TAVI) gains increasing acceptance, cardiologists and surgeons are exploring additional patient populations who may benefit from the procedure. A new paper in the Journal of the American College of Cardiology provides the first look at the use of TAVI in the small but important group of patients with pure, severe native aortic valve regurgitation (NAVR) who do not have aortic stenosis.

The authors acknowledge that TAVI will likely be used sparingly in the NAVR population:

…although these results are encouraging for those patients who are truly ineligible for surgery, surgical valve replacement remains the gold standard for those who can undergo it, even at high risk. Furthermore, there is an increasing number of patients in whom the native aortic valve can be preserved during surgery.

Click here to read the full story on Forbes.

400 Patients Sue Kentucky Hospital and 11 Cardiologists Over Unnecessary Procedures Reply

After undergoing more than two dozen cardiac procedures over a period of twenty years at St. Joseph Hospital in London, Kentucky, a patient was told by an outside cardiologist in Lexington that a recent procedure had been performed unnecessarily on an artery that was barely blocked.

“I would have not carried out this procedure,” the cardiologist, Michael R. Jones, wrote in a letter to the patient. The story is recounted  in an article published on Sunday in USA Today and the Louisville Courier-Journal, about the latest and perhaps the biggest case yet to surface over unnecessary cardiac procedures.

Comment: By sheer coincidence, on the same day, the New York Times published a news analysis by Barry Meier about the scandal over Johnson & Johnson’s hip implant. “Doctors Who Don’t Speak Out” focuses on the failure of physicians to report problems with devices and drugs, but clearly the issue has even larger implications. A quote from Harlan Krumholz in the story– “Questioning the status quo in medicine is not easy”– could easily apply to the many recent cases of egregious overuse of cardiac procedures and devices. Imagine how recent history might have been different if colleagues of  Sandesh Patil and Mark Midei had raised earlier questions about borderline procedures. Cardiologists and other physicians complain about the intrusive and burdensome role played by the legal system, regulators, and insurance companies, but they have only themselves to blame if they refuse to police their own ranks, and indeed tacitly participate in a system that provides lucrative compensation to high-volume proceduralists.

Click here to read the entire post on Forbes.

Kentucky

St. Jude Raises The Stakes In Renal Denervation With An Outcomes Study Reply

 

The already hot field of renal denervation for resistant hypertension just got a little hotter. With the announcement of a clinical trial powered to detect improvements in cardiovascular outcomes, St. Jude Medical has raised the stakes.

“To date, the renal denervation studies that have been conducted only looked at reducing blood pressure in patients with uncontrolled or resistant hypertension,” said Michael Böhm, a principal investigator for the trial, in a St. Jude press release. “What we need to know is if this minimally invasive approach for treating hypertension also correlates to a reduction in major cardiac events such as heart attack, stroke and death, which are the primary risks for patients whose blood pressure is not well controlled.”

 Click here to read the entire post on Forbes.

St Jude EngligHTN Rendal Denervation System

St Jude EngligHTN Rendal Denervation System

 

Amid Rising Tide Of Diabetes More Patients Reach Treatment Goals Reply

There’s a glimmer of good news amidst all the recent bad news about diabetes. Although the prevalence of diabetes has doubled over the last generation, more people today  are reaching their treatment goals than in the past. New data from the National Health and Nutrition Examination Surveys (NHANES), published online today in Diabetes Care, show that efforts to control hemoglobin A1C, blood pressure, and LDL cholesterol in patients diagnosed with diabetes have achieved some success, but they also demonstrate that there’s enormous room for improvement.

Click here to read the full post on Forbes.

العربية: جهاز قياس غلوكوز الدم. Česky: Glukome...

FDA Approves Second Generation MRI-Friendly Pacemaker System Reply

Medtronic announced today that the FDA had approved its Advisa DR MRI SureScan, a next generation pacemaker system specifically designed and tested for use with MRI scanners. The system, which Medtronic said would be launched immediately, includes the Advisa MRI device and two CapSureFix MRI SureScan leads.

 Click here to read the full post on Forbes.

Medtronic Advisa

‘Bias in choosing the question is a much bigger issue than lying about the data’ Reply

Robert Califf takes questions about conflict of interest from Harlan Krumholz. Here are a few choice quotes. Read the entire Q&A on CardioExchange.

…focusing exclusively on the medical products industry and failing to consider other sources of conflict of interest is a huge mistake and leads to sensationalism that then engenders reactive rules that add to bureaucracy rather than addressing the real issues.

…a despotic, egotistical principal investigator can be just as dangerous as a controlling funding organization. Like our constitution, trials need a balance of power…

Bias in choosing the question is a much bigger issue than lying about the data.

…lying about the data is rare. Lying by omission (not looking at aspects of the data) is much more common.

‘Somebody has finally twigged that the heart and the lungs are joined up to each other and live in this space called the chest…’ 1

Here are a few gems from Richard Lehman’s weekly cardiovascular literature review. Read the whole thing on CardioExchange.

On a JAMA study showing that ramipril increases walking time in patients with intermittent claudication:

This is the kind of trial that makes nobody millions of dollars, but which we should all be doing in our fields of interest. It took just three interested hospitals in Southern Australia.

On a NEJM study studying rivaroxaban in acutely ill medical patients:

Rule One for selling reprints is that you make the conclusion of the Abstract as favourable as possible, because this is all that most clinicians read…

On Lancet study showing a close association between pneumonia and cardiovascular disease:

Golly, somebody has finally twigged that the heart and the lungs are joined up to each other and live in this space called the chest, or thorax. This could have major implications. We could start thinking of providing services for elderly breathless patients rather than making them wander from chest physicians to cardiologists and back again: we could tackle the problem of the post-hospital syndrome by attending to the cardiovascular risks of chest infections and the right ventricular contribution to heart failure; we could even ask patients what their main problems are and whether they are sufficiently addressed to make them feel safe at home. But all this requires a level of genius far beyond the reach of any known health service.

 

 

ACC And STS Break New Ground To Test TAVR For Unapproved Uses Reply

In a startling break with tradition, the American College of Cardiology and the Society of Thoracic Surgeons will manage and run their own clinical trials testing expanded uses for transcatheter aortic valve replacement (TAVR). The two medical groups have recently been granted an investigational device exemption (IDE) by the FDA for one such trial and hope to gain an IDE for at least two more trials. The news was first reported by The Gray Sheet (subscription required) on February 8.

The new development represents a significant enlargement of the TVT registry, already run by the ACC and STS, which tracks all TAVR usage in the US.

Click here to read the entire post on Forbes.

ACC STS TVT logo

Seeking Cardiovascular Safety Data, FDA Blocks Approval Of Novo Nordisk’s Long-Acting Insulin Reply

The FDA informed Novo Nordisk on Friday that it would not approve the company’s highly anticipated long-acting insulin degludec products (Tresiba and Ryzodeg) until it receives data from a cardiovascular outcomes trial. Approval of the drugs had been widely anticipated for this year, following a positive recommendation from an FDA advisory committee last fall. But the committee also unanimously recommended that the company be required to perform a cardiovascular outcomes trial.

Click here to read the complete article on Forbes.

 

 

 

Rivaroxaban Effective In Medically Ill Patients But At High Bleeding Cost Reply

The recent arrival of novel oral anticoagulants has provided important new options for venous thromboembolism (VTE) treatment and prevention. New indications for these drugs have been granted for patients with atrial fibrillation and following orthopedic surgery. But an additional indication, for acutely ill medical patients at risk for VTE, does not appear likely in the near future, as a new trial published in the New England Journal of Medicine shows that one of these novel drugs, though effective at preventing VTE, also resulted in a significant increase in bleeding risk.

In the Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin (MAGELLAN), first presented at the American College of Cardiology meeting in 2011, more than 8,000 medically ill patients were randomized to subcutaneous enoxaparin for 1o days or oral rivaroxaban for 35 days.

Click here to read the full post in Forbes.

Should Radial Artery Access Be The Default Choice For PCI? Reply

Over on CardioExchange six cardiologists, from fellows to senior faculty, talk about whether radial artery access should be the “default choice for PCI:

Megan Coylewright, MD, MPH (interventional fellow, Mayo Clinic): …radial PCI should be a part of every interventionalist’s toolkit…

Micah Eimer, MD (cardiologist, Glenview, IL): The data are pretty convincing on the lower rate of complications, and my clinicial experience confirms that. Patients who have undergone both radial and femoral approaches consistently and strongly prefer the radial approach…

L. David Hillis, MD, (Chair, Department of Internal Medicine) and Richard Lange, MD (Professor, University of Texas Southwestern Medical School): As old dogs (admittedly late in learning new tricks), we’re a part of “Gen-S” (“S” for Sones)… In Texas, where everything is bigger and better, we don’t feel a need to abandon the femoral approach.

Click here to read the entire discussion on CardioExchange.

Large Study Finds Genetic Links To Aortic Valve Calcification Reply

A genetic component is believed to play an important role in valvular heart disease, but the specific genes involved have not been identified. Now an interntional group of researchers has identified genetic variations that increase the risk for valvular calcification.

In a paper published in the New England Journal of Medicine, members of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium report on their search for genes associated with aortic valve calcification and mitral annular calcification in several of study cohorts. They found one SNP, in a gene previously shown to be associated with lipoprotein(a) levels and the risk of coronary artery disease, to be significantly associated with a doubling of the risk for aortic-valve calcification. This finding was replicated in additional cohorts.

Click here to read the full story on Forbes.

Back To The Future: Resurrected Data From 1960s Trial Might Impact Contemporary Dietary Fat Debate 2

In an exceedingly strange turn of events, data from a clinical trial dating from the 1960s, long thought to be lost, has now been resurrected and may contribute important new information to the very contemporary controversy over recommendations about dietary fat composition.

The American Heart Association has long urged people to increase their consumption of polyunsaturated fatty acids (PUFAs), including omega 6 PUFAs, and reduce their consumption of  saturated fatty acids. The recommendations are based on the simple observation that PUFAs lower total and LDL cholesterol while SFAs have the opposite effect. However, the cardiovascular effects of substituting PUFAs for SFAs have never been tested in randomized, well-controlled clinical trials, and a growing proportion of experts now suspect that simple changes in total cholesterol and LDL cholesterol may not tell the whole story.

One trial that actually tested the hypothesis was the Sydney Diet Heart Study, which ran from 1966 through 1973. In the trial, 458 men with coronary disease were randomized to a diet rich in linoleic acid (the predominant omega 6 PUFA in most diets) or their usual diet. Although total cholesterol was reduced by 13% in the treatment group during the study, all-cause mortality was higher in the linoleic acid group than in the control group. However, in the original publications, and consistent with the practice at the time, deaths from cardiovascular (CVD) and coronary heart disease (CHD) deaths were not published.

Now, in a new paper published in BMJ, Christopher Ramsden and colleagues report that they were able to recover and analyze data from the original magnetic tape of the Sydney Diet Heart Study. The new mortality findings are consistent:

Click here to read the full story on Forbes.

Delorean DMC-12

ACE Inhibitor Improves Walking In People with Peripheral Artery Disease Reply

Giving an ACE inhibitor to people with peripheral artery disease (PAD) and intermittent claudication reduces pain and increases walking time, according to a new study published in JAMA. Currently the pharmacologic options for this patient population are few and have limited efficacy.

Researchers at three Australian hospitals randomized 212 patients with PAD to receive the ACE inhibitor ramipril or placebo for 24 weeks. Compared to the patients on placebo, patients on the ACE inhibitor had a mean 75 second increase in their pain-free walking time (156 seconds in the placebo group versus 229 seconds in the ramipril group, p<0.001) and a 255-second increase in their maximum walking time (259 seconds in the placebo group versus 512 seconds in the ramipril group, p<.001).  The ACE inhibitor was also associated with improvements in other secondary measures of walking and physical quality of life.

Click here to read the full story on Forbes.

Patients waiting at the clinic. PARAGUAY.

Should Physicians Be Business Partners With Medical Device Salesmen? Reply

Should a Florida cardiologist co-own a business running frozen yogurt shops with a medical device salesman? That’s the question raised by reporter John Dorschner in a story posted by the Miami Herald yesterday:

 

“Mark Sabbota, a Hollywood cardiologist, regularly implants $5,000 pacemakers in patients at Memorial hospitals in South Broward — generating, last year alone, more than a half-million dollars in sales for a manufacturer called St. Jude Medical.

Sabbota, public records show, also happens to be partners with a St. Jude sales rep in two corporations that run frozen yogurt shops.”

 

Click here to read the full story on Forbes.

 

English: Yogurt, Yogurtland, Frozen Desserts

 

 

European Heart Journal Retracts Main Paper Of The Kyoto Heart Study 1

The editors of the European Heart Journal have retracted the 2009 paper reporting the main results of the Kyoto Heart Study, a randomized, open-labeled study testing the add-on effect of valsartan to conventional therapy in high-risk hypertension. The retraction notice gave no details about the problems that led to the retraction. Here is the full text of the retraction notice:

“This article has been retracted by the journal. Critical problems existed with some of the data reported in the above paper. The editors of the European Heart Journal hereby retract this paper and discourage citations of it.”

Click here to read the full story on Forbes.

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No Sunshine For Continuing Medical Education 1

After many long delays, CMS today released the final details of the Sunshine Act. Starting next September all pharmaceutical and device companies will be required to publicly report payments made to US physicians.

 

However, there is at least one very major exception to this requirement. Although the initial draft of the rules stated that payments made, directly or indirectly, to physicians speaking at continuing medical education (CME) programs would need to be reported, this part of the rule has now been substantially weakened. According to the final rule, companies will not be required to report payments to speakers at accredited CME events as long as the companies don’t select the speakers or directly pay them. In other words, accredited third party CME providers will be entirely exempt from reporting payments to speakers.

 

Click here to read the full story on Forbes.

 

Solar Eclipse