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.

Click here to read the full post on Forbes.

 

 

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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:

Click here to read the full post on Forbes.

 

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.

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)

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.

 

 

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.

Click here to read the full post on Forbes.

 

 

Heart Failure: The Missing 800 Pound Gorilla In Diabetes Trials Reply

Is heart failure the missing 800 pound gorilla in diabetes trials? That’s the argument proposed by a group of  prominent cardiovascular and diabetes researchers.

It was long believed that by virtue of their glucose-lowering properties diabetes drugs would confer substantial cardiovascular benefits. Now, however, that belief is no longer widely held and the FDA now requires cardiovascular outcome trials for new diabetes drugs. But, write the researchers in  an article published in The Lancet Diabetes & Endocrinology, these trials are failing to track and analyze one key cardiovascular endpoint, thereby diminishing the value of these trials in assessing the cardiovascular effects of diabetes drugs.

Click here to read the full post on Forbes.

 

European Setback For Novartis Heart Failure Drug Reply

European regulators have dealt a setback to a novel heart failure drug under development by Novartis.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended against giving market approval to serelaxin (Reasanz) for the treatment of acute heart failure. The recommendation is based largely on the committee’s analysis of the RELAX-AHF trial, which was published in the Lancet in 2012. Here is CHMP’s explanation for their decision:

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FDA Advisory Panel To Review New Heart Failure Drug From Novartis Reply

A novel acute heart failure drug from Novartis will be evaluated next month by an FDA advisory committee, perhaps countering a long string of crash-and-burn cardiology drugs. On February 13 the FDA’s Cardiovascular and Renal Drugs Advisory Committee will discuss the biologics license application (BLA) for serelaxin injection from Novartis. The indication is for the improvement of the symptoms of acute heart failure through reduction of the rate of worsening of heart failure. (The meeting notice has been posted in the Federal Register but has not yet appeared on the FDA website.) Last year the drug received a “breakthrough therapy” designation from the FDA.

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Can Personalized Medicine And An Adaptive Trial Design Salvage This Hard Luck Drug? Reply

Arca Biopharma today announced that it had received FDA clearance to start a phase 2B/3 trial of its novel beta-blocker, Gencaro (bucindolol) for the prevention of atrial fibrillation in patients with heart failure. The GENETIC-AF trial has all the hallmarks of the modern era: the drug will only be tested in patients with a genetic variation that the company believes may predict a positive response to the drug. And the trial will be one of the first to utilize the much-discussed “adaptive” trial design, starting as a phase 2B study and then possibly expanding to a phase 3 study after an interim analysis of the trial data.

But if GENETIC-AF represents the very model of a modern drug, it also serves as a good example of the pitfalls of drug development. Because this drug has been around for a very long time and has had a very troubled history.

Click here to read the full story on Forbes.

 

Michael Bristow, Arca Biopharma President and CEO

 

CardioMEMS Heart Failure Device Gets Mixed Reception From FDA Advisory Panel Reply

The FDA’s Circulatory System Devices Panel sent a mixed message to the FDA today about CardioMEMS Champion HF Pressure Measurement System.  The small implantable device provides provides daily pulmonary artery pressure measurements to guide physicians in their treatment of patients with congestive heart failure.

In December 2011 the same panel voted 9-1 that the device was safe, 7-3 that the device had not been shown to be effective, and 6-4 that the benefits did not outweigh the risks. Now, two years, later, the vote wasn’t much different: the panel agreed unanimously (11-0) that the device was safe; 7-4 that it had not been shown  to be effective, and 6-4-1 that the benefits outweighed the risks.

Click here to read the full story on Forbes.

 

CardioMEMS wireless sensor with quarter

 

Study Raises Questions About Digoxin Use Today Reply

Digitalis is one of the oldest medicines in the cardiovascular arsenal. When William Withering identified digitalis as the active ingredient in the foxglove plant more than 200 years ago he was only codifying a longstanding folk remedy for heart failure, or “dropsy” as it was known then.

Digitalis fully entered the modern era with the publication of the DIG trial in 1997. The trial found that digitalis reduced hospitalization for heart failure but did not have an impact on mortality. On the basis of the trial digitalis received recommendations in the US and European guidelines for use in patients with systolic heart failure who remain symptomatic despite optimal therapy. However, the epidemiology and treatment of heart failure have evolved considerably since then. Now the authors of a new study, supported by an accompanying editorial, say that these recommendations need to be reconsidered.

In a study published in Circulation: Cardiovascular Quality and Outcomes, James Freeman and colleagues followed 2,891 patients with newly diagnosed systolic heart failure, 18% of whom received digitalis. After 2.5 years the digoxin users had a higher rate of death and hospitalization for heart failure…

Click here to read the full post on Forbes.

 

Study Fails To Support Broader Patient Population For Cardiac-Resynchronization Therapy Reply

Cardiac-resynchronization therapy (CRT) has been shown to be beneficial in heart failure (HF) patients with a wide QRS interval. These benefits have not been reproduced so far in patients with narrow QRS intervals, though many such patients have ventricular dyssynchrony. Now a new study, presented at the European Society of Cardiology in Amsterdam and published simultaneously in the New England Journal of Medicine, once again has failed to find benefits for CRT in a broader patient population.

The EchoCRT Study Group randomized HF patients with a QRS duration < 130 msec and left ventricular dyssnchrony upon echocardiography. All patients received a CRT-D device; half the patients were randomized to have the CRT feature activated.

The study was stopped prematurely after 809 patients had been randomized and followed for nearly 20 months.

Click here to read the full story on Forbes.

Automatic Wireless Monitoring Shows Benefits in Chronic Heart Failure Reply

Following in the wake of studies that failed to find benefits associated with remote wireless monitoring of heart failure (HF) patients, the In-Time trial, presented at the European Society of Cardiology meeting in Amsterdam, is the first trial to show that home monitoring of HF patients may be beneficial.

Gerhard Hindricks, the coordinating investigator of the trial, said that In-Time was designed to test whether automatic remote home monitoring can detect events that precede clinical events and thereby spark interventions to help reduce hospitalizations for HF. In the trial, 664 chronic HF patients with an indication for an ICD were randomized to home monitoring plus standard care or standard care alone.

Click here to read the full story on Forbes.

 

 

 

Faint PRAISE: 13 Year Delay In Publication Of A Major Clinical Trial Sparks Criticism Reply

13 years after first being presented the results of the PRAISE-2 trial finally have been published in JACC: Heart Failure. The trial itself is now largely irrelevant to current clinical practice, as the hypothesis it tested has long been abandoned, but the long delay in publication may serve to bring even more awareness to the issue of the delay or complete absence of publication of many clinical trials.

An accompanying editorial, by Marc Pfeffer and Hicham Skali, is highly critical of the delay:

Although standards for conduct and reporting of clinical trials have improved since 2000, the failure to fully vet the results of a clinical trial of human volunteers in a peer-reviewed journal was and remains unacceptable.

PRAISE-2 had its origins in the first PRAISE trial, which was first presented in 1995 and subsequently published in the New England Journal of Medicine in 1996. In that trial there was no difference between amlodipine (Norvasc, Pfizer) and placebo in the rate of mortality or cardiovascular hospitalization in patients with heart failure. However, a prespecified subgroup analysis turned up the highly surprising result that heart failure patients with a nonischemic etiology who received amlodipine had a highly significant 46% reduction in the risk of death compared with placebo patients.

Click here to read the full post on Forbes.

Milton Packer

Milton Packer

Novel Heart Failure Drug From Novartis Gains ‘Breakthrough Therapy’ Designation From FDA 1

Serelaxin, the novel therapy under development for the treatment of acute heart failure, has received a “breakthrough therapy” designation from the FDA, according to Novartis, the company developing the drug. The designation, the FDA explains, “is intended to expedite the development and review of drugs for serious or life-threatening conditions” and requires “preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.” In addition to getting a speedier review process, the sponsor of a drug with the designation receives “more intensive FDA guidance” on the development program.

Click here to read the full story on Forbes.

 

Interpretations Differ Over Study Of Coenzyme Q10 In Heart Failure Reply

Coenzyme Q10 (CoQ10) may be beneficial in heart failure, according to the results of the Q-SYMBIO study presented this past weekend at the Heart Failure 2013 meeting in Lisbon, Portugal. But the results should be viewed with a critical eye, say experts.

Click here to read the full post on Forbes, including a comment from Milton Packer.

 

European Medicines Agency Starts Review of Combined Use Of Drugs That Block The Renin-Angiotensin System 1

The European Medicines Agency said last week that it was initiating a review of the combined use of agents that block the renin-angiotensin system (RAS). The three classes of RAS-blocking drugs (ACE inhibitors, ARBs, and direct renin inhibitors) are used to treat hypertension and congestive heart failure.

The EMA said that the review was being performed to address concerns that combined RAS-blocking drugs could increase the risk for hyperkalemia, hypotension, and kidney failure when compared with a single agent.  A recent meta-analysis of 33 clinical studies published in the British Medical Journal concluded that “although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events… The risk to benefit ratio argues against the use of dual therapy.”

Franz Messerli, senior author of the BMJ meta-analysis, applauded the EMA action and said that “as usual the FDA is dragging its feet.”

Click here to read the full story on Forbes.

 

 

 

Study Questions Role Of Dual-Chamber ICDs For Primary Prevention Reply

Dual-chamber ICDs are implanted in a majority of primary prevention patients without a pacing indication who receive an ICD. Although there are a number of theoretical advantages with dual-chamber devices, these devices are more likely to cause complications. Although CMS requires providers to justify the medical necessity of dual-chamber devices, current guidelines from the AHA/ACC and HRS do not specify a single-chamber device.

In a new study published in JAMA, Pamela Peterson and colleagues analyzed data from 32,000 primary prevention patients without a pacing indication who were enrolled in the National Cardiovascular Data Registry (NCDR). 38% received a single-chamber device and 62% received a dual-chamber device. At 1 year there wereno significant differences in mortality, all-cause hospitalization, or heart failure hospitalization between the two groups. However, patients in the dual-chamber group had a higher risk of complications, including a highly significant increase in the 90 day risk of mechanical complications requiring reoperation (1.43% in the single-chamber group versus 2.02% in the dual-chamber group, p < 0.001). A very similar pattern emerged when the investigators performed an analysis that matched patients in the two groups with a propensity model. The analysis suggested “that the choice of a dual-chamber device is relatively random with respect to patient characteristics.

Click here to read the full story on Forbes.

 

 

FDA Warns That Tolvaptan Can Lead To Serious Liver Injury 1

The FDA has issued a drug safety communication concerning tolvaptan (Samsca, Otsuka), a selective vasopression V2-receptor antagonist used in heart failure patients to treat clinically significant hypervolemic and euvolemic hyponatremia. The FDA said tolvaptan “should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially leading to liver transplant or death. “

The liver injury risk was discovered in clinical trials testing tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD). The drug label has been updated and now states that use of the drug should be limited to 30 days and that it is no longer indicated in patients with cirrhosis. The FDA recommended that tolvaptan should be discontinued in patients with liver disease who are currently taking the drug.

 

 

BLOCK HF: CRT Superior To Conventional Pacing In Heart Failure Patients With AV Block Reply

 

Patients with atrioventricular (AV) block generally receive right ventricular pacing; cardiac resynchronization therapy (CRT) has been restricted to patients with a low ejection fraction and a wide QRS duration. However, RV pacing may worsen LV dysfunction in AV block patients with low ejection fractions. Previous studies have raised the possibility that these patients may benefit from biventricular pacing with a CRT device.

Now, results from the Medtronic-sponsored BLOCK HF (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) trial, published in the New England Journal of Medicine, lend more support for the expansion of CRT devices into this population. Anne Curtis and colleagues randomized 691 patients to standard RV pacing or  biventricular pacing. After 37 months of followup, a primary outcome event– death, urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the LV end-systolic volume index– occurred in 55.6% of the RV pacing group versus 45.8% in the biventricular pacing group (HR 0.74, CI 0.60-0.90).

Click here to read the full post on Forbes.

 

Anne Curtis

 

 

 

 

Another Negative Trial With Darbepoetin Alfa 1

Once again a trial testing the erythropoiesis-stimulating agent darbepoetin alfa (Aranesp, Amgen) has produced a negative result. Results of the RED-HF (Reduction of Events by Darbepoetin Alfa in Heart Failure) trial were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.

A total of 2278 patients with systolic heart failure and mild-to-moderate anemia were randomized to darbepoetin alfa (Aranesp, Amgen) or placebo. As expected, treatment with darbepoetin alfa significantly improved hemoglobin levels. However, no significant improvements in outcomes were associated with darbepoetin alfa.

Click here to read the full story on Forbes.