New Study Lends Support For Alternative Heart Attack Treatment Strategy Reply

It is generally agreed that the best treatment for heart attack patients is to immediately reperfuse the blocked artery with a stent. But many people live in areas where this strategy, known as primary PCI, is not available within the time frame when it produces the greatest benefit. Previous studies have found good short term outcomes in patients who receive a pharmaco-invasive strategy, in which patients first receive fibrinolytic therapy including a clot-busting drug and then later undergo angiography. Now long-term results from a large real-world study show that this strategy may be an acceptable alternative for some patients when immediate primary PCI is not available.

In a paper published in Circulation, French researchers report the 5 year mortality findings from nearly 1,500 STEMI patients enrolled in the 2005 cohort of FAST-MI (The French Registry on Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction).

Click here to read the full post on Forbes.

 

About these ads

Will Edwards Snatch Defeat From The Jaws Of Its Victory Over Medtronic? Reply

On the heels of a sweeping victory in the courts over its rival MedtronicEdwards Lifesciences is poised to dominate the TAVR (transcatheter aortic valve replacement) market– the revolutionary new catheter technology that offers some patients with life-threatening aortic valve disease an alternative to chest-splitting surgery. Although the legal wrangling is not quite over– Medtronic is appealing the decision and has requested that enforcement of the injunction be postponed– it appears likely that Edwards will ultimately achieve a broad legal and business victory.

But Edwards’ unprecedented victory also presents an unprecedented challenge to the company. While the court appears to have given Edwards everything it wished, the ultimate result could produce significant harm to Edwards’ relationship to the interventional cardiologists who are its core customers. More importantly, there is now a distinct possibility that at least for several years many people who could possibly benefit from the Medtronic technology will not be able to get it.

A Decisive Victory

In last week’s ruling a federal judge delivered a broad ruling in favor of Edwards:

Click here to read the full post on Forbes.

 

FDA Grants Fast Track Status To Amgen Heart Failure Drug Reply

Amgen announced yesterday that its new chronic heart failure drug ivabradine had been granted fast track status by the FDA. The company said the fast track designation, which is for drugs that treat serious conditions and fill an umet medical need, will aid the development and speed the review of the drug.

Click here to read the full post on Forbes.

 

New Medtronic Heart Valve Threatened By Court Decision Reply

A legal injunction may severely limit the availability in the United States of Medtronic’s CoreValve device, which only received FDA approval earlier this year. The device received abundant praise recently when a large clinical trial demonstrated substantial advantages for CoreValve over traditional open-heart surgery.

The injunction is the latest episode in an ongoing patent war in which Edwards Lifesciences, which pioneered the field of transcatheter aortic valve replacement with its Sapien devices, has sought to hinder Medtronic from competing in the US and international markets.

Click here to read the full post on Forbes.

 

The Uncertain Future Of A Once Highly Promising Device For Lowering Blood Pressure Reply

Following the spectacular crash and burn of the Symplicity HTN-3 trial at the American College of Cardiology two weeks ago, the future of renal denervation (RDN)– the once highly promising catheter technology that many thought would cure resistant hypertension– appears in doubt.

Although the device has not been approved in the US– and will not be approved without further clinical trials– in Europe and other places it remains on the market. So the questions about the technology’s future revolve around the future direction of research in the field and how the existing renal denervation market will be affected by the trial results.

Click here to read the full post on Forbes.

 

Lancet Editors Raise More Questions About Prominent Harvard Stem Cell Researcher Reply

There’s more trouble for Piero Anversa, the prominent and controversial stem cell researcher.

Today the Lancet issued an expression of concern about an influential, much-cited stem cell paper. As first reported by Retraction Watch, an investigation at Harvard Medical School and Brigham and Women’s Hospital has raised concerns about the integrity of data coming from Piero Anversa’s laboratory at the Brigham contained in the 2011 SCIPIO study published in the Lancet.

Here is the full Expression of Concern issued by the Lancet:

Click here to read the full post on Forbes.

 

Cardiology And The Medicare Data Avalanche Reply

The avalanche of data released by Medicare on Wednesday was followed shortly by an avalanche of news reports about the data. Here’s a review of some of the more significant cardiology-related details that came out in these stories.

Cardiology was the third in New York Times list of total Medicare payments received by the highest-paid 2% of doctors. This 2% accounted for nearly one-fourth of total Medicare payments. There were 2,176 cardiologists in the top 2% group and they received more than 1.6 billion dollars from Medicare. Ahead of cardiologists at the top of the list were ophthalmologists (2,995 providers who received more than $3.3 billion) and hematologists/oncologists (1,831 providers who received more than $2 billion).

The Washington Post‘s Wonkblog asked the top 10 Medicare billers to explain their charges…

Click here to read the full post on Forbes.

 

Troubled NHLBI TOPCAT Trial Disappoints Reply

Although a significant portion of people with heart failure have preserved ejection fraction, none of the proven heart failure therapies has been shown to be beneficial in this important and growing heart failure subpopulation. Now a new NHLBI-funded study has failed to find a benefit in this group for spironolactone, which is a cornerstone of therapy for heart failure patients with reduced ejection fraction. But trial investigators and heart failure experts believe it is too early to dismiss hope that spironolactone and other aldosterone antagonists– including Pfizer’s Inspra (eplerenone)– may eventually be found to work in this population.

TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), published in the New England Journal of Medicine, randomized 3,445 patients with heart failure with preserved ejection fraction (HFPEF) to either spironolactone or placebo.

Click here to read the full post on Forbes.

 

Circulation Retracts Paper By Stem Cell Pioneer And Its Own Editor Reply

Following an investigation by Harvard Medical School and Brigham and Women’s Hospital a 2012 paper published in Circulation has been retracted. The “institutional review… determined that the data are sufficiently compromised that a retraction is warranted.” The two senior authors of the paper are Piero Anversa, a pioneering researcher in cardiac stem cells, and Joseph Loscalzo, the editor-in-chief of Circulation and the chairman of the department of medicine at the Brigham.

Click here to read the full post on Forbes.

 

Study Suggests Link Between Viagra And Melanoma Reply

In recent years researchers have uncovered a potentially important pathway whereby PDE5A inhibitors (which include sildenafil– Viagra– and other drugs used to treat erectile dysfunction and pulmonary hypertension) could potentially increase the risk of developing melanoma. Now a new study provides early evidence showing an association between sildenafil and melanoma, though, like all observational studies, it is unable to demonstrate a cause-and-effect relationship.

Click here to read the full post on Forbes.

 

Title: Pathology: Patient: Melanoma Descriptio...

 

Boehringer Ingelheim’s Pradaxa Gains New Indication 1

The new oral anticoagulants continue to gain additional indications from the FDA. Earlier today Boehringer Ingelheim announced that the FDA had approved Pradaxa (dabigatran) for the treatment of venous thromboembolism (VTE), which includes both deep venous thrombosis (DVT) and pulmonary embolism (PE).

 Click here to read the full post on Forbes.

 

 

Cardiovascular Disease Declines in Rich Countries but Grows Elsewhere Reply

A new Global Cardiovascular Disease (CVD) Atlas portrays a divided world where rich countries are gradually freeing themselves from the yoke of CVD but where many poor and middle-income countries are still struggling.

Ischemic heart disease and stroke were the two biggest contributors to the global burden of disease in 2010, accounting for 5.2% and 4.1%, respectively, of all disability adjusted life years (DALYs)….

Click here to read the full post on Forbes.

 

A New Novartis Heart Failure Drug Might Be A Blockbuster Reply

I try to avoid using words like “blockbuster” and “breakthrough” when writing about new drugs and treatments. I’ve been disappointed too many times. But, though they’ve been in short supply lately in cardiovascular medicine, sometimes there really are breakthroughs and blockbusters. In my career writing about cardiovascular medicine I’ve seen the introduction of the ACE inhibitors, statins, stents, ICDs, and clopidogrel, among others. All of these became multibillion-dollar products. Now there’s a new candidate that just might join this group. I’ll tell you why, but I can’t emphasize strongly enough that right now we only have extremely preliminary information. So be warned. And don’t be completely surprised if it does bomb out. We’ve been down this road before.

As I reported previously (here and here), early on Monday Novartis disclosed that the PARADIGM-HF trial testing LCZ696, a novel, first-in-class Angiotensin Receptor Neprilysin Inhibitor (ARNI), had been stopped early. As I later found out, the news was even better than Novartis had said in its press release. I spoke with the co-principal investigator of the trial, Milton Packer, who told me that the trial had been stopped because of a highly statistically significant reduction in cardiovascular mortality in patients taking LCZ696 instead of the current gold standard of treatment, an ACE inhibitor. Marc Pfeffer, a cardiologist at the Brigham and Women’s Hospital with long experience in heart failure, told me that he interprets “the stopping of a major clinical outcome trial for effectiveness by an experienced DSMB [Data and Safety Monitoring Board] as indicating that the final results will be both definitive and important.”

The first thing to know is that a reduction in cardiovascular mortality is a really big deal….

Click here to read the full post on Forbes.

 

 

Novartis Trial Was Stopped Early Because Of A Significant Drop In Cardiovascular Mortality 1

The largest-ever trial in heart failure was stopped early because of a highly statistically significant reduction in cardiovascular mortality, according to one of the trial’s two primary investigators.

Earlier today I reported that the PARADIGM-HF trial testing LCZ696, a novel, first-in-class Angiotensin Receptor Neprilysin Inhibitor (ARNI), had been stopped early because the trial had demonstrated a significant reduction in the combined primary endpoint of cardiovascular death and heart failure hospitalization. This information was taken from a Novartis press release.

But it turns out that the press release wasn’t entirely accurate. For once, a company appears to have actually downplayed a positive finding in its trial….

Click here to read the full post on Forbes.

English: Mohawk Stop Sign

English: Mohawk Stop Sign (Photo credit: Wikipedia)

Aspirin and Clonidine Fail to Help Surgery Patients Reply

Heart attacks (myocardial infarctions) are among the most common and serious side effects of noncardiac surgery. An effective regimen to minimize this risk has been the subject of considerable debate in recent years. The controversy was recently exacerbated because the recommendation to use beta-blockers in this setting was based on research which has now been discredited. Substantial evidence against the use of perioperative beta blockers came from the original POISE trial.

Now a second POISE trial, the Perioperative Ischemic Evaluation 2 (POISE-2) trial, casts doubt on the value of two other proposed strategies to reduce death and MI in patients undergoing noncardiac surgery. Results of POISE-2 were presented at the American College of Cardiology meeting in Washington, DC and published simultaneously in two papers in the New England Journal of Medicine.

Click here to read the entire post on Forbes.

 

Early Success For Novel Novartis Heart Failure Drug Reply

A large clinical trial testing a novel compound from Novartis for chronic heart failure has been stopped early for efficacy. In a press release Novartis said the Data Monitoring Committee had recommended early closure of the PARADIGM-HF trial because the trial had demonstrated a significant reduction in the combined primary endpoint of cardiovascular death and heart failure hospitalization.

PARADIGM-HF randomized patients with heart failure and reduced left ventricular ejection fraction to either the ACE inhibitor enalapril or LCZ696, an Angiotensin Receptor Neprilysin Inhibitor (ARNI) that is the first in its class.

Click here to read the full post on Forbes.

 

 

High-Sensitivity Troponin Test Could Identify Low Risk Chest Pain Patients In The ED Reply

Approximately 15-20 million people in Europe and the United States go to the emergency department every year with chest pain. Many can be discharged early if they are not having an acute coronary syndrome. A large new single-center observational study, presented at the American College of Cardiology meeting in Washington, DC and published simultaneously in the Journal of the American College of Cardiology, provides fresh evidence that high-sensitivity cardiac troponin T (hs-cTnT) may be useful in helping identify chest pain patients in the emergency department who do not need to be admitted to the hospital.

Click here to read the full post on Forbes.

 

MADIT-CRT Long-Term Follow-Up Shows Survival Benefit with CRT-D Reply

MADIT-CRT was an influential trial that showed a reduction in heart failure complications — but not mortality — when cardiac resynchronization therapy (CRT) was added to an implantable defibrillator in patients with mild heart failure who also had left bundle-branch block (LBBB). Patients in the trial were followed for 2.4 years, raising questions about the long-term effects of CRT. Now, a second look at 854 patients who participated in a follow-up study, presented at the American College of Cardiology and published in the New England Journal of Medicine, suggests that over the long term, CRT may save lives in this population. MADIT-CRT was sponsored by Boston Scientific.

Click here to read the full post on Forbes.

 

 

 

MADIT-CRT Long-Term Follow-Up Shows Survival Benefit with CRT-D

First TAVR Comparison Trial Favors Sapien XT Over CoreValve Reply

With two devices now approved for transcatheter aortic valve replacement (TAVR), the marketing battle has begun to win the hearts and minds of cardiologists. On Saturday at the ACC, Medtronic gained bragging rights showing the first mortality benefit for its CoreValve device. A similar improvement did not occur in the PARTNER trials with the Edwards Sapien device, but all the experts have warned against cross-trial comparisons. Now an actual randomized trial has emerged comparing the two platforms. The results favor the Sapien XT, but the size and scope of the trial mean that the discussion and debate will certainly continue.

Click here to read the entire post on Forbes.

 

 

Survival Advantage for TAVR Over Surgery in High-Risk Patients Reply

Transcatheter aortic valve replacement (TAVR), which has been slowly and cautiously entering the clinical arena, will probably get a big boost from a new trial showing a significant mortality advtange for TAVR over traditional surgery.

Results from the U.S. CoreValve High-Risk Study were presented at the American College of Cardiology in Washington, DC, and published simultaneously in the New England Journal of Medicine.

Click here to read the full post on Forbes.

 

 

No Benefit Found in First Real Test of Renal Denervation Reply

SYMPLICITY HTN-3, the eagerly awaited first rigorous test of renal denervation, shows that the real effect of the novel blood-pressure-lowering technology is dramatically lower than earlier expectations, which had been fueled by data from previous uncontrolled trials. Results of SYMPLICITY HTN-3 were presented at the American College of Cardiology conference in Washington, DC, and published simultaneously in the New England Journal of Medicine.

Click here to read the full post on Forbes.

 

New Atrial Fibrillation Guideline Supports New Drugs And Devices Reply

A new guideline for atrial fibrillation (AF) was released on Friday by the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society. Among other features, the 2014 Guideline for the Management of Patients With Atrial Fibrillation incorporates important new information about the new oral anticoagulants and catheter ablation for the treatment of AF symptoms.

Click here to read the entire story on Forbes.

 

Guest Post: How Sure Can We Be About Optisure? 2

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.

How Sure Can We Be About Optisure?

by Edward J. Schloss, MD

On March 24, St. Jude Medical announced the global launch of the Optisure family of ICD leads. It’s been a while since a new ICD lead was launched, and I’m probably not the only one who was caught by surprise. I’d like to explore why this approval is important for the ICD community. First, a brief history of ICD leads from St. Jude.

FROM RIATA TO DURATA

St. Jude Medical developed its own line of ICD leads after it purchased the former ICD vendor Ventritex in 1996. The first-generation Riata lead, approved in 2001, was succeeded by the Riata ST line in 2006. These leads were distinguished, in part, by their thin diameter, permitting implantation through a 7 Fr introducer sheath. In that era, implanting physicians’ interest in a thin lead was very strong. Even the high-profile failure of the 7 Fr Medtronic Fidelis ICD lead didn’t seem to dampen that enthusiasm.

Both of St. Jude’s Riata lead families later developed problems. Reports of subacute perforation soon after implant in the Riata ST line arose in the late 2000s. A year or two later, the internal core structure of both the Riata and Riata ST leads was discovered to break down in 25% and 10%, respectively, of these leads, as evident on fluoroscopic evaluation — a process called externalization. This problem, along with noted increased electrical failures of this lead, prompted an FDA class I recall of both product lines in December 2011, in addition to intense scrutiny and discussion in the lay press, investor press, blogosphere, and academic literature.

By the time the Riata and Riata ST leads were recalled, St. Jude had already gotten approval and marketed the successors: Riata ST Optim and, later, the Durata lead. Both these leads shared design similarities with the Riata ST lead, but additional modifications were intended to prevent the failures that the predecessor lines had exhibited. To mitigate the perforation risk specifically, changes in the Durata lead were intended to minimize tip pressure to the myocardium. And both new leads had a new insulator wrapping around the silicon core from Riata ST. This Optim insulation, shown to be more resistant to abrasion, has apparently been successful at preventing the fluoroscopic externalization that had occurred with the earlier leads.

The failure of the Riata leads has been shown to be time-dependent, so the device community has expressed some concern about Durata’s future performance. In addition, FDA has continued to apply pressure, with a January 2013 warning letter about this lead, specifically noting problems detected during a California plant inspection. Early active registry studies of Durata have been highly favorable, but a limited number of Durata problems have been discussed in case reports. Noted ICD critic Dr. Robert Hauser has also reported on a series of Durata failures from the FDA MAUDE database.

INSIDE THE DURATA

The Durata and Riata ST may share some failure mechanisms. In particular, the Swerdlow case report revealed inside–out abrasion under the distal shocking coil, resulting in a short between that coil and the ring-electrode cable, and consequent oversensing. Swerdlow and the Hauser MAUDE study have suggested that a similar form of insulation failure at the proximal shocking electrode could result in failure to defibrillate. (Because Durata and Riata ST have essentially the same internal design and materials at the level of the shocking coils, it is possible that this failure mechanism will occur with the newer leads.)

Moreover, Swerdlow found evidence of disruption of the Optim layer, which he hypothesized was due to Optim degradation, possibly related to hydrolysis of the polymer and cyclical stresses during the 4 years of lead service. The long-term biostability of Optim is critical, because without the Optim layer, the Durata leads are quite similar to Riata ST.

St. Jude has staunchly defended Durata, citing the favorable active registry data and additional testing in a large bibliography on its website. The company’s independent engineering analysis concluded that Swerdlow’s lead was damaged externally as a result of the extraction tools, not Optim degradation (counter to Swerdlow’s assertion).

THE BASICS ABOUT OPTISURE

St. Jude released Optisure this week, its first new ICD lead line since Durata. The product literature describes Optisure as “providing an additional system enhancement for addressing lead complications and improving system reliability.” The company says the slightly thicker 8 Fr lead is “for physicians who prefer a larger lead diameter.”

According to St. Jude, Optisure is built on the basic design of Durata with these additional modifications:

  • 8 Fr lead body
  • additional Optim insulation at the proximal end of the lead
  • new layer of Optim insulation under the SVC shocking coil

FDA filings show Optisure was submitted for approval as a PMA (pre-market approval) supplement on 10/24/12 and approved for release on 02/21/14. The filing links back to the original PMA for the Ventritex TVL lead issued in 1996. It does not appear that a human clinical trial was performed, as is common in PMA supplement approvals.

MY ANALYSIS OF OPTISURE

I’m happy that ICD companies continue to pursue process improvement. If we ever reach the point when we think we have a lead that is “good enough,” that will be really unfortunate. I’ve continued to have some concerns about Durata. ICD lead failures in the Riata lines have not become evident until 4 years of use, and we are only recently accumulating large numbers of Durata leads that have been implanted that long. Fortunately, Optisure’s design attempts to directly address two of the feared possible failure mechanisms of the Durata lead.

First, the increased Optim thickness in the proximal lead is likely to diminish the can/lead abrasion in the pocket, and perhaps in areas of cyclical stress. I find it really ironic and satisfying to read that St. Jude is promoting Optisure “for physicians who prefer a larger lead diameter.” Back in 2010, when I criticized thin ICD leads in an HRS debate, I had a hard time getting people to agree with me. Now, going thicker is a marketing strategy. Times really have changed.

Second, the Optim layer under the proximal shocking coil should help to prevent internal shorts that could cause lead failure. This type of short, if it involves the distal high voltage cable, is especially worrisome, as it may manifest only at the time of clinical or induced ventricular fibrillation. I fear that proximal coil HV shorting may be responsible for many of the Riata and Durata lead failures and deaths documented in MAUDE database entries, such as those published by Hauser (as well as this more recent report). Having a layer of Optim between the silicone core and the SVC shocking coil should help to prevent this shorting, just as it has prevented externalization. Unfortunately, this mitigation will not change the likelihood of shorting under the RV coil (as in Swerdlow’s case) but should help overall lead reliability. St. Jude seems to feel the same way, citing Optisure’s design as an “enhancement for addressing lead complications and improving system reliability.”

WHAT’S NEXT FOR ICDs?

Getting a pacemaker or ICD lead designed, approved, and built is an enormous undertaking. The process has only become more difficult because of increasing regulatory barriers. The formerly common process of PMA supplement approval has come under greater scrutiny. ICD and LV leads that formerly might have been approved under PMA supplement now require large U.S. trials. The trials’ costs, coupled with the fear of another Fidelis or Riata debacle, appear to have stifled lead innovation. Given the development of two new of leadless pacemakers (now being implanted in Europe) and the U.S.-approved subcutaneous ICD, we may be at the beginning of the end of the era of transvenous cardiac leads.

I have to agree with Zheng and Redberg that the PMA supplement process for medical device approval is problematic. The fact that leads from Riata to Optisure were approved on the basis of a dissimilar lead developed by a different company nearly 20 years ago should be ample evidence of this argument. Should Riata leads have gone through a clinical trial? Answering yes may seem logical. The unfortunate reality, however, is that no pre-market clinical trial would have picked up this lead’s late and novel failure mechanism. Even today, I would argue that careful industry engineering and close post-market scrutiny (including FDA-mandated registries) are doing far more to help our ICD patients than any pre-market trial ever could.

Nevertheless, it is critical to improve existing products, especially ICD leads. Most of us agree these are the “weak link in the chain.” I fear that a more highly regulated environment is having the paradoxically adverse effect of forcing us to settle with what we already have. That’s why I tweeted on March 24 that the quick approval of Optisure “both surprises and pleases me.” I wonder if this lead would even have been developed if it had been forced through a long, expensive clinical trial. Would that outcome have been a good thing?

FDA Advisory Panel Recommends Against Approval Of Novartis Heart Failure Drug Reply

The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted unanimously (11-0) against approval of the biologics license application (BLA) for serelaxin (proposed trade name Reasanz). The novel drug from Novartis was intended to be used in patients with acute heart failure. The once highly-promising drug, which received a ”breakthrough therapy” designation from the FDA last year, was also turned down for approval in Europe earlier this year.

Click here to read the entire post on Forbes.

 

 

Glucose Measurements Don’t Improve Cardiovascular Risk Assessment Reply

Although blood glucose and glycated hemoglobin (HbA1c) play a central role in diabetes, the value of these measurements to assess cardiovascular risk has been unclear. Now, in a paper published in JAMA, members of the Emerging Risk Factors Collaboration analyze data from nearly 300,000 people without known diabetes or cardiovascular disease who were enrolled in 73 prospective studies.

Click here to read the full post on Forbes.