Yeah right LMAO !!
unless he spoke 5x & even then....probably not.... LMAO..again !!
How's everyone doing with Entresto?
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Yeah right LMAO !!
unless he spoke 5x & even then....probably not.... LMAO..again !!
Attributed to Novartis hype for a likely niched drug due to that crafty trial design.
Essentially, last line therapy! Great job Novartis Managed Care.
The primary end point, a composite of cardiovascular death or hospitalization for HF, favored the ARNI drug. Most important, overall death was lower in the ARNI vs enalapril group at 17% vs 19.8%, respectively.
There is no other way to describe PARADIGM other than to say it was a positive trial. Most heart-failure experts are enthusiastic. Mainstream media, too, are sold. And only hours after the FDA approved the drug, I received an upbeat email from a Novartis sales representative.
The ocean breezes and warm sun of Barcelona also had its effect on me. I was initially positive on the trial. Among other strengths, I noted the large numbers of patients in both groups; the good baseline CHF therapy; biologic plausibility of neprilysin inhibition; and the highly significant P values.
Time for thought and reflection is a potent elixir in the practice of medicine. I feel differently now. Closer inspection of the trial and discussion with experts in methodology have led me to these 10 reasons for caution.
The new ARNI drug might prove to be as successful in the real world as it did in the clinical trial. Maybe. But the real world is a place where drugs aren't free and where patients aren't always young, male, and screened with run-in periods.
In elementary school, I learned that replication of astounding results is a tenet of good science. We don't seem to need that anymore when it comes to clinical science. That's too bad, because the history of medicine is replete with examples where we let hope, bias, and marketing get the best of us.
Do not dismiss the problem of cost and distraction. When we spend money on one therapy, we have less for other therapies. When we spend precious bandwidth in the clinic speaking about expensive new pills, we have less time to promote the basics of health.
I am not against progress. History may prove that combining valsartan and sacubitril was a great idea. The early signs are positive. But years of practicing electrophysiology have taught me the value of slow medicine. So slowly is how I will proceed with this new class of chemicals.
There is no other way to describe PARADIGM other than to say it was a positive trial. Most heart-failure experts are enthusiastic. Mainstream media, too, are sold. And only hours after the FDA approved the drug, I received an upbeat email from a Novartis sales representative.
The ocean breezes and warm sun of Barcelona also had its effect on me. I was initially positive on the trial. Among other strengths, I noted the large numbers of patients in both groups; the good baseline CHF therapy; biologic plausibility of neprilysin inhibition; and the highly significant P values.
Time for thought and reflection is a potent elixir in the practice of medicine. I feel differently now. Closer inspection of the trial and discussion with experts in methodology have led me to these 10 reasons for caution.
- The active arm of PARADIGM featured a high dose of valsartan against a low to moderate dose of enalapril. Was angiotensin blockade equivalent? Was enalapril a straw-man comparator?
- PARADIGM had an active run-in phase in which 12% of patients dropped out. There are no active run-in phases out here in the real world.
- PARADIGM enrolled a select group of young patients. The mean age was 63 years; 80% were male, and only 6% were black. How does that cohort generalize to the millions of elderly, female, and nonwhite CHF patients with comorbid diseases?
- The absolute difference in death rate was 2.8% over 2.5 years. The translation: 97.2% of patients experienced the same result—they did not die.
- PARADIGM was terminated early. That fact introduces bias.
- More than 1000 centers randomized patients in PARADIGM-HF. That requires a lot of quality control over the raw data.
- More patients in the ARNI group experienced low blood pressure. Any clinician knows low blood pressure is a major problem in CHF treatment, especially in the elderly and those with comorbidities.
- A group of European authorsraised concern that neprilysin inhibition of β-amyloid peptide could increase amyloid deposition in the brain and predispose to dementia. These authors concede no cognition issues were seen in PARADIGM, but they also noted the 2.5-year trial was not designed to assess a problem that may accrue over the long term. (Drugs don't affect just the heart.)
- Cost is another reason for pause. Some estimates have valsartan/sacubitril costing over $4500 per year.comorbid diseases.[4] The conversations, I am afraid, will focus on the new chemical rather than the powerful effects of old-fashioned therapies, such as exercise, diets, and attention to sleep.
The new ARNI drug might prove to be as successful in the real world as it did in the clinical trial. Maybe. But the real world is a place where drugs aren't free and where patients aren't always young, male, and screened with run-in periods.
In elementary school, I learned that replication of astounding results is a tenet of good science. We don't seem to need that anymore when it comes to clinical science. That's too bad, because the history of medicine is replete with examples where we let hope, bias, and marketing get the best of us.
Do not dismiss the problem of cost and distraction. When we spend money on one therapy, we have less for other therapies. When we spend precious bandwidth in the clinic speaking about expensive new pills, we have less time to promote the basics of health.
I am not against progress. History may prove that combining valsartan and sacubitril was a great idea. The early signs are positive. But years of practicing electrophysiology have taught me the value of slow medicine. So slowly is how I will proceed with this new class of chemicals.
Joel Kahn, M.D.
A Tale of Two Heart Failure Trials
Posted: 07/16/2015 5:05 pm EDT Updated: 07/16/2015 5:59 pm EDTIn September of 2014 the Paradigm-HF study was released in a prestigious journal. This study of moderate to severe CHF in 8,442 patients with weak heart function was funded by Novartis and compared a new combination agent versus a gold standard drug enalapril. The study was stopped early after 27 months because the new drug resulted in a primary outcome rate of 22 percent vs 26 percent with enalapril. Fewer patients died in follow up on the new agent (17 percent vs. 20 percent). There were more episodes of low blood pressure and allergic swelling with the new agent.
In contrast, in December of 2014 the results of the Q-SYMBIO trial were published in a respected journal. This groundbreaking study examined the outcome of 420 patients with moderate to severe CHF supplemented with Coenzyme Q10 (CoQ10) 300 mg a day or placebo. The primary study endpoint at two years was reached by 15 percent in the CoQ10 group versus 26 percent in the placebo group. Cardiac mortality was nine percent vs. 16 percent in the two groups. Adverse effects were not observed with CoQ10.
What has happened since the two trials were published, both hopeful advances in treating CHF? The Paradigm-HF study has led to the FDA approval of the combination agent as Entresto and pharmaceutical representatives will soon be calling on my office to teach and encourage me to use it. At a yearly cost of $4,500, Entresto is expected to be a $5 billion dollars a year drug for Novartis. And what about CoQ10? Sadly, the results will not be taught to doctors at lunches and dinners. Just follow the money to find out why. CoQ10 cannot be patented and many companies make it over the counter. CoQ10 is not found in hospital pharmacies and is not prescribed by most doctors. A patient bringing CoQ10 into the hospital is likely to have it taken away or sent to the pharmacy to be repackaged and returned at some point.
Two important studies on CHF, two very different implementations. Fortunately the digital age has made it possible for many patients to search the internet, read the Q-SYMBIO trial, and start the supplement on their own. All my patients are discharged from the hospital on it and have a blood level drawn to insure they are absorbing it. Spread the word, it is not all just expensive urine that results from selected supplementation of nutrients.
A Tale of Two Heart Failure Trials
Posted: 07/16/2015 5:05 pm EDT Updated: 07/16/2015 5:59 pm EDTIn September of 2014 the Paradigm-HF study was released in a prestigious journal. This study of moderate to severe CHF in 8,442 patients with weak heart function was funded by Novartis and compared a new combination agent versus a gold standard drug enalapril. The study was stopped early after 27 months because the new drug resulted in a primary outcome rate of 22 percent vs 26 percent with enalapril. Fewer patients died in follow up on the new agent (17 percent vs. 20 percent). There were more episodes of low blood pressure and allergic swelling with the new agent.
In contrast, in December of 2014 the results of the Q-SYMBIO trial were published in a respected journal. This groundbreaking study examined the outcome of 420 patients with moderate to severe CHF supplemented with Coenzyme Q10 (CoQ10) 300 mg a day or placebo. The primary study endpoint at two years was reached by 15 percent in the CoQ10 group versus 26 percent in the placebo group. Cardiac mortality was nine percent vs. 16 percent in the two groups. Adverse effects were not observed with CoQ10.
What has happened since the two trials were published, both hopeful advances in treating CHF? The Paradigm-HF study has led to the FDA approval of the combination agent as Entresto and pharmaceutical representatives will soon be calling on my office to teach and encourage me to use it. At a yearly cost of $4,500, Entresto is expected to be a $5 billion dollars a year drug for Novartis. And what about CoQ10? Sadly, the results will not be taught to doctors at lunches and dinners. Just follow the money to find out why. CoQ10 cannot be patented and many companies make it over the counter. CoQ10 is not found in hospital pharmacies and is not prescribed by most doctors. A patient bringing CoQ10 into the hospital is likely to have it taken away or sent to the pharmacy to be repackaged and returned at some point.
Two important studies on CHF, two very different implementations. Fortunately the digital age has made it possible for many patients to search the internet, read the Q-SYMBIO trial, and start the supplement on their own. All my patients are discharged from the hospital on it and have a blood level drawn to insure they are absorbing it. Spread the word, it is not all just expensive urine that results from selected supplementation of nutrients.
Yes, but they represent the "voice of the payer"! I guess Novartis Sr Management isn't listening or Birch doesn't really have a pair to stand up against unrealistic expectations.