Until launch

it (this diovan combo) was only like 5% difference than 35 year old vasotec, read the freakin data you dunce & how many HF patients are only on enalapril anyway? this will make tekturna look like the 2nd coming, you brainwashed lemmings are rather comical

 

If this lie will help you sleep at night, believe what you will. This product will be HUGE in HF and is very much needed. If you knew anything about HF, it is the SOC to compare to an ACEI that actually has the indication.

Anyone here not excited to sell this should leave and make way for well trained, non elitest experience CV/Hospital Sales professionals in the HF space.

We will all gladly sell this dug with mortality and hospitalization reductions, with decent safety profile when HF is such a hot topic with healthcare reform.

Some of you internal don't know a thing about this market. Please go before you F+*&% up the biggest thing in HF in 20 years.

Really...you are one dumb F+*&%. You should get off cafepharma and get on medscape and cardiosource and read up on this from the thought leaders on HF.

Maybe Novartis should just outsource licensing to real CV/Hosp reps. As investor, I would have no faith reading the venom being spewed about your company, your leadership and your perception of this product.

YOU are the reason this industry has problems, though I am sure it is much easier for you to blame others for your lack of preparation and accountability. Hope you never have a family member with heart failure.

 

Mortality morbidity data is not much different than diovan. Nice try. Must be on the brand

 

$4 Altace is just as good

 

Add a $1 BB & it's better

 

Hey Bozo did you take off your big red nose & floppy shoes yet? Why do you think they have the annual "purge" of reps. So brainwashed morons like you imbibed in kool aid can find a new generation of minds to indoctrinate with some overpaid hired gun hack's stacked study that finds the absolute lowest form of comparison.

"Vinay Prasad, MD MPH
Many have hailed the novel compound LCZ696 as the next great advance in heart failure (HF) treatment, on the heels of findings from the newly published PARADIGM-HF trial. I think this is too generous an interpretation.

LCZ696 is itself a combination of two drugs: valsartan (an angiotensin-receptor blocker) and sacubutil (an inhibitor of neprilysin). During a median follow-up of 27 months, LCZ696 showed superiority to enalapril with respect to the primary composite endpoint (death from cardiovascular causes and hospitalization for HF) and all-cause mortality — with a number needed to treat of 35. (These findings are likely exaggerated, given that the trial was stopped early, but that is not my primary concern with this study.)

Here are three reasons to doubt that PARADIGM-HF sets a new standard both for treatment of HF and for randomized comparative-effectiveness studies:

1. Drug Dosing

In PARADIGM-HF, oral enalapril was dosed up to 10 mg twice daily, whereas LCZ696 was dosed up to 200 mg twice daily (which includes a cumulative 320 mg of valsartan). The problem is that 320 mg is the maximum HF dose of valsartan per drug labeling, but enalapril can be dosed up to 40 mg daily (20 mg twice daily) — double the maximum dose proscribed per protocol.

The actual administered mean dose of the two drugs was 375±71 mg for LCZ696 and 18.9±3.4 mg for enalapril. Not surprisingly, given that the LCZ696 group received more angiotensin-pathway blockade, mean systolic blood pressure was lower in that group (3.2±0.4 mm Hg lower than in the enalapril group).

In effect, drug dosing in PARADIGM-HF was a “straw man” comparison. The reported outcomes may be entirely a consequence of more ARB versus less ACE inhibitor. That is reason enough to doubt the findings. Sacubutil, the novel drug, could have been a sugar pill, and the results may well have turned out the same. But there are two more good reasons to be skeptical."

 

PART 2

2. Drug Run-In Periods

Drug run-in periods are a controversial study-design choice — one that I believe must unequivocally be abandoned. In PARADIGM HF, patients with systolic HF were asked to stop the ACE inhibitor or ARB they were already on and take oral enalapril 10 mg twice daily for 2 weeks. Of the 10,513 patients who entered the run-in phase, 1102 (10.5%) discontinued treatment at this point. Then the remaining 9412 patients took LCZ696 for more than twice as long (4 to 6 weeks), during which 977 (10.4%) patients discontinued treatment and 8442 underwent randomization.

The reason why drug run-in periods are problematic is discussed at length in the literature. In short, run-in periods exclude intolerant and nonadherent patients, foster spuriously large treatment effects, and (most troubling) create inclusion criteria that are irreproducible — i.e., that apply to no population we can clearly describe, as reasons for dropout are multifaceted and unique.

Even more concerning is that drug run-in periods test a different question than the one we think we are testing. In PARADIGM-HF, the run-in tested whether sticking with LCZ696 or switching to enalapril is better for HF patients who have taken and tolerated enalapril followed by LCZ696. It effectively turns the trial into a withdrawal study. If stopping LCZ696 is harmful, that counts against enalapril.

3. Stopping What Already Works

All PARADIGM-HF participants were already on an ACE inhibitor and an ARB, the standard of care for systolic dysfunction supported by several randomized trials — and they were asked to stop. Those of us who care for HF patients know quite well that there often is a very good reason why patients end up taking the ACE or ARB they are currently using. It makes little sense to stop what is working to enter this trial.

Here are some better options for how PARADIGM-HF could have been conducted:
•Option A: Compare the novel combo drug with valsartan alone (same dose of valsartan) among patients with newly diagnosed HF.
•Option B: Test sacubutil (the novel drug) against placebo as add-on therapy for patients with HF who are already on an ARB. This is the cleanest option.
•Option C: Randomize patients with HF to either continue their current therapy (and ramp up the dose to the maximal drug-label dose) or switch to the combination drug.

The Real Lesson of PARADIGM-HF

The response to PARADIGM-HF has been positive partly because it has been a long time any new drug has been shown to improve mortality in patients with HF. But our desire to find better options for these patients does not mean we should lower the standards for what counts as a good trial. Few providers would consider a randomized trial comparing valsartan at 320 mg with enalapril at 20 mg to be fair — and adding a novel drug to the valsartan does not make this comparison more palatable. Instead, PARADIGM HF shows that with a large number of patients and the “right” trial design, you can get any conclusion you want. As William Randolph Hearst said, “You furnish the pictures, and I’ll furnish the war.”

PARADIGM-HF does convince me that more angiotensin-pathway blockade is better, but it does not prove the benefit of a novel drug. A history of negative HF trials should teach us that the pretest probability that a novel drug works is very low in HF. The data from PARADIGM-HF do not greatly alter the probability that the drug works.

The concerns I have highlighted cannot be remedied, even with full access to the study data (which should nevertheless be made available) — instead, they are hard-wired into the trial design. For that reason, we must ask for another randomized trial — one that is truly done right. Heart failure patients deserve no less.

 

Wow, you can also quote ignorant articles. One that his own peers admonished as ignorant. I really hope you were not placed in a job. Clearly if you are using this as your defense, you are clueless about current clinical treatment realities and will fail. Which, I am sure you are used to.

 

Wow. 1 Cardiologist sited...have you checked into this "academic" and all the other negative claims he makes about multiple clinical trials? Fact is this was a well done trial, well explained as to why dosing of ACEI was 20mg a day (if you knew anything about the CV segment you would know this is the most tolerated dose and is the studied dose in all landmark CV trials that use enal as a comparator as SOC. Again, please please leave and let proven CV Hosp salespeople have these jobs or use this time before launch to read up on all editorial my well respected international HF experts. Read up on the clinical programs in HF to date and realize that while this drug won't sell itself this will be a huge benefit to a large number of REF HF patients and even if a 2a guideline it will be a much needed addition especially now with HCR imperatives. Please, please leave! Do everyone the favor- your defeatist attitude as you are going into what will be the most important launch in cardiology in over 20 years is mind boggling.

 

Packer STFU & do your Dallas power couple thing .......hack

MALVINDER PARMAR, MD | Physician - INTERNAL MEDICINE |
TIMMINS ON Canada
September 10, 2014

Is PARADIGM-HF sufficient to cause paradigm shift?
The dose of the two comparator agents was not equivalent between the two groups. The maximal dose of angiotensin receptor blocker (valsartan 320 mg a day) with addition of another agent, a neprilysin inhibitor (sacubitril), was compared to a moderate dose of enalapril (20 mg versus 40 mg a day). As expected, the mean blood pressure in the valsartan + sacubitril group was 2.7 mmHg lower than the enalapril group. Could this bias have resulted in this effect?

More patients with advanced heart failure (class III & IV) were in enalapril (25.5%, n=1076) group than in the valsartan + sacubitril (23.9%, n = 1002) group. Could the degree of heart failure be responsible for this difference?

Finally, 4 of the 11 (36%) authors listed are employees of Novartis (the maker of the drug and sponsor of the trial), and one of these authors (JG) did not disclose the conflict of interest.

Based on the data presented, the limitations of study, and potential bias in the design of the trial and potential conflict of interest, one cannot positively conclude that the effect seen in this study is truly because of the neprilysin inhibitor, or because of the weaker comparator.

 

William Foster | Physician - Anesthesiology | Disclosure: None

August 30, 2014

Unintended consequences
While the success of the PARADIGM-HF trial is welcome news, a degree of caution is warranted. It should be kept in mind that the natriuretic peptides are not the only substrates of neprilysin. Among its substrates is beta-amyloid, a peptide strongly linked to Alzheimer's Disease (AD). It seems reasonable to suspect that inhibition of neprilysin might lead to an increased level of beta-amyloid and thus an increased risk of AD. In fact, knockout mice lacking the gene for neprilysin show an accelerated development of amyloid plaques and neurobehavioral abnormalities.The PARADIGM-HF study did not address this issue, and indeed was terminated far too quickly (27 months) for a proper assessment. Patients treated with neprilysin inhibitors should be closely monitored for neurological dysfunction, lest we end up trading congestive heart failure for Alzheimer's.

 

Can you say combo with patch

 

hey sh$t bag, if you want to read public approval sh$t the look for serious follow-up answers, don't place anonymous posts on a public chat board. You want serious conversation, earn it, or friggin' pay for it.

 

Play with your dingle berries

 

Oh go f?ck yourself loser!!!

 

You can get a second job like my abl, JP

 

Who's JP?

 

Jeff Prejean he is a manager for the Nola district and a joke