European Review Confirms Increased Risk with Ivabradine Reply

Following a review provoked by troubling findings that emerged from a large clinical trial, the European Medicines Agency (EMA) is making several recommendations intended to lower the risk of heart problems linked to the heart-rate-lowering drug ivabradine. The drug is marketed by Servier in Europe under the brand names of Corlentor and Procoralan and is indicated for the treatment of heart failure and stable angina. The drug is not available in the U.S. but is under development by Amgen for the indication of heart failure.

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SIGNIFY Trial Provokes Sound And Fury Over Controversial Servier and Amgen Drug Reply

The controversial drug ivabradine just got a little more controversial. The drug, which is marketed by Servier under the brand names of Corlentor and Procoralan, is available in Europe and elsewhere and is used for the treatment of heart failure and stable angina. The drug is not available in the US, but it is under development by Amgen for a heart failure indication.

Now a very large new study presented at the European Society of Cardiology meeting in Barcelona and published simultaneously in the New England Journal of Medicine has found no evidence of benefit in a stable angina population and found more adverse events associated with the drug and even suggested the likelihood of harm in a very large and important trial subgroup. The findings have resulted in an investigation by the European Medicines Agency, placing a cloud over the future status of the drug.

Click here to read the full post on Forbes.

 

Silencio! Claiming Pressure From European Regulators, Trial Leaders Cancel Press Conference Reply

Investigators of the much-anticipated and controversial SIGNIFY trial have told the European Society of Cardiology leadership that they will not participate in a previously scheduled press conference on Sunday at the society’s main meeting in Barcelona. But they say they will present the main results of their trial at a Hot Line session later in the afternoon.

According to the ESC, the SIGNIFY investigators, who include Kim Fox, Ian Ford, Philippe Gabriel Steg, Jean-Claude Tardif, Michal Tendera, and Roberto Ferrari, told the ESC leadership that regulators at the European Medicines Authority (EMA) had told the investigators that because they (the investigators) were scheduled to appear before the EMA they should not discuss or comment on their trial outside the official presentation at the ESC conference.

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PARADIGM-HF Establishes a New Paradigm for Heart Failure Treatment Reply

So far as I can tell the only problem with PARADIGM-HF is that the results are so good that it’s boring. Anyone interested can reasonably assume that what they hear or read about PARADIGM-HF — and cardiologists will be seeing and hearing an awful lot about it —  will be overwhelmingly positive.

Briefly, the trial did everything its sponsor (Novartis) and its investigators (led by Milton Packer and John McMurray) hoped. It met all its major endpoints in all the subgroups without raising any sort of a safety signal. If the findings are confirmed after a rigorous FDA review, then Novartis will likely have a blockbuster on its hand.

All the excitement is over a new drug still known only by its number, LCZ696.

Click here to read the full post on Forbes, including a detailed interview with Milton Packer.

 

Predicting PARADIGM-HF, Or What To Expect When You’re Expecting Reply

The wait is almost over. For the last 5 months the most eagerly awaited trial in the cardiovascular universe has been PARADIGM-HF, the large (8,500 patient) trial of a new and novel heart failure drug from Novartis. If reality lives up to the early hope and hype, the drug, LCZ696, could completely reshape the heart failure landscape and give Novartis that rarest of gems, a new and genuine blockbuster cardiovascular drug.

The main results of the trial will first be presented at a press conference in Barcelona, Spain this Saturday in connection with the annual meeting of the European College of Cardiology.

Click here to read the full post on Forbes.

 

Study Offers Little Support for an Old Drug Reply

Digoxin is one of the oldest drugs in the cardiovascular arsenal, derived from the foxglove plant and first described in the 18th century by William Withering. It is frequently used in patients with heart failure (HF) and with atrial fibrillation (AF). The few trials supporting its use were performed in HF patients before newer treatments arrived. There have been no good trials in AF.

A new observational study published in the Journal of the American College of Cardiology now provides the most detailed perspective on digoxin use in AF. …

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J Am Coll Cardiol. 2014; 64(7): 660-668.

 

 

Principal Investigator Of Suspended Cytori Stem Cell Trials Remains Hopeful Reply

Shares of Cytori Therapeutics took a big bit hit today after the company disclosed in a press release that it had suspended enrollment in its ATHENA and ATHENA II trials. This kind of news is never a good sign, but the   principal investigator of the trial tells me that he believes the current problems are surmountable and that the trials are still viable.

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Januvia Linked To Increase in Heart Failure Hospitalizations Reply

The cardiovascular effects of drugs used for glucose control in patients with diabetes have been a subject of controversy for many years now. More recently, attention has started to focus specifically on the risk for heart failure. Now, an observational study will likely raise new questions about the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin (Januvia, Merck).

In a paper published in JACC Heart Failure, Daniala Weir and colleagues analyzed insurance claims from a database of more than 7600 patients with diabetes and heart failure.

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ESC Hot Lines: First Real Data On Promising Novartis Heart Failure Drug Reply

The first real details about the much-anticipated novel new heart failure drug from Novartis will kick off this year’s Hot Line sessions at the annual meeting of the European Society of Cardiology in Barcelona, Spain. The meeting runs from August 30 until September 3.

As I have previously reported, the PARADIGM-HF trial was stopped because of a highly statistically significant reduction in cardiovascular mortality in patients taking LCZ696 (a novel, first-in-class Angiotensin Receptor Neprilysin Inhibitor) instead of the current gold standard of treatment, an ACE inhibitor….

Here is the complete list of Hot Line trials:

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Positive Results For New Oral Drug From Actelion Reply

Actelion has announced positive top-line results for a phase III trial of a new oral drug for the treatment of pulmonary arterial hypertension (PAH). The drug, selexipag, is a first-in-class orally available selective prostacyclin IP receptor agonist.

The pivotal, double-blind GRIPHON study was the largest outcome trial ever performed in PAH. 1,156 PAH patients were randomized to selexipag or placebo. The company said that trial had “met its primary efficacy endpoint with high statistical significance.”

Click here to read the full post on Forbes.

 

Sharp Scrutiny From European Medicines Agency Of Amgen And Servier Heart Drug Reply

There may be trouble on the horizon for ivabradine, a heart drug marketed by Servier under the brand names of Corlentor and Procoralan. The drug is widely available in Europe and elsewhere, though it is not available in the US, where it is under development by Amgen. Although it hasn’t been widely noticed– I can find no other press reports– the European Medicines Agency said that it has started a review of the drug based on troubling findings from the SIGNIFY study. (Ivabradine is used to treat patients with long-term stable angina and long-term heart failure.)

The main results of SIGNIFY are scheduled to be presented on August 31 at the European Society of Cardiology meeting in Barcelona. But on May 8 the European Medicines Agency announced that it had initiated a review of ivabradine based on  preliminary results…

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Prophylactic ICDs Appear Effective In Less Severe HF Patients Reply

ICDs are routinely implanted in heart failure patients with ejection fractions (EFs) of 35% and lower to prevent sudden cardiac death. However, the benefits in patients at the higher end of the spectrum– between 30% and 35%– have not been well demonstrated in clinical trials, since few patients in this range have been enrolled in clinical trials.

Now a new study published in JAMA suggests that the benefits in this group are similar to the benefits in heart failure patients with more severely depressed EFs.

Click here to read the full post on Forbes.

 

FDA Approves Novel Implanted Sensor To Monitor Heart Failure Reply

The FDA announced today that it had approved the CardioMEMS Champion HF System. The small implantable device provides daily pulmonary artery pressure measurements to guide physicians in their treatment of  NYHA Class III heart failure patients who have been hospitalized for heart failure in the previous year. The system consists of three parts: a small permanent sensor implanted in the pulmonary artery, a catheter-based delivery system, and a system that acquires and processes PA pressure measurements from the implanted monitor and transfers the data to a secure database.

Click here to read the entire post on Forbes.

 

FDA Rejects Novel Novartis Drug For Acute Heart Failure Reply

Novartis said today that the FDA had issued a complete response letter for the biologics license application for RLX030. The drug, also known as serelaxin, is a recombinant form of the naturally occurring human hormone relaxin-2, which has been found to help women adjust to the cardiovascular changes that occur during pregnancy.

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Stem Cell Therapy To Fix The Heart: A House Of Cards About To Fall? Reply

For more than a decade cardiac stem cell therapy has attracted an enormous amount of attention, promise, and research dollars. Now an original and important new study published in BMJ finds that many of the most promising results in the field are illusory and that the potential benefits of stem cells to treat heart disease are probably far more modest than we’ve been led to believe. The study also raises disturbing questions about ethics and research conduct (and misconduct) in a high-flying field.

Researchers in the UK, led by Darrel Francis, closely scrutinized 133 reports from 49 different clinical trials testing autologous bone marrow stem cells in patients with heart disease. They found an astonishingly large number  of discrepancies in the reports– altogether more than 600  discrepancies, ranging from minor oversights to serious unexplained errors and apparent deceptions. Many errors were mathematical or statistical errors while others were more general, such as conflicting descriptions of studies as either a prospective randomized trial or a retrospective observational study.

The key finding of the study is that there was a very strong correlation between the number of discrepancies in a study and the reported improvement in heart function as measured by left ventricular ejection fraction(LVEF)…

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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.

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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.

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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….

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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)

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.

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

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.

 

 

FDA Reviewers Recommend Against Approval For Novartis Heart Failure Drug 1

Ahead of an important advisory panel FDA reviewers have recommended against approval of a novel drug for acute heart failure from Novartis. The once highly-promising drug, which received a ”breakthrough therapy” designation from the FDA last year, was turned down for approval in Europe earlier this year.

On Thursday the FDA’s Cardiovascular and Renal Drugs Advisory Committee will discuss the biologics license application (BLA) for serelaxin injection (proposed trade name Reasanz) from Novartis.

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Phase 4 Actelion Study Misses Primary Endpoint Reply

Actelion announced today that a phase 4 study with its blockbuster drug bosentan (Tracleer) had failed to meet its primary endpoint.

The COMPASS-2 trial was a prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of bosentan on the time to first confirmed event in patients with symptomatic pulmonary arterial hypertension (PAH) already receiving treatment with sildenafil.

Click here to read the full post on Forbes.

 

4 Deaths Linked To Thoratec Heart System Reply

Thoratec Corporation today issued an urgent safety advisory about a serious problem with a key component of the HeartMate II LVAS system. The company said 4 patients had died and 5 patients had a loss of consciousness or other symptoms of hypoperfusion. The episodes occurred when patients and caregivers “experienced difficulties with the process of changing from a primary system controller to their backup system controller.”

The company said that 8 of the 9 events “occurred in patients who were converted to the Pocket Controller after being originally trained on an older model, the EPC System Controller….

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HeartMate II

 

 

FDA Investigating Heart Failure Risk Linked To Onglyza Reply

The FDA said today that it was conducting an investigation of a possible increased risk for heart failure associated with the diabetes drug saxagliptin. Saxagliptin is marketed by AstraZeneca as Onglyza and Kombiglyze XR. (AstraZeneca recently completed the purchase of all rights to the drug from its manufacturer, BristolMyers-Squibb.)

The investigation stems from findings from the cardiovascular outcomes trial SAVOR-TIMI 53 trial  in which more than 16,000 type 2 diabetics were randomized to the DPP-4 inhibitor saxagliptin or placebo.

Click here to read the full post on Forbes.