Search This Blog

Tuesday, September 3, 2019

As Genfit readies liver drug for market, founding CEO makes way for new blood

As Genfit hopes for phase 3 trial successes and future filings for its liver disease drug, its long-term CEO and co-founder Jean-François Mouney is stepping aside and promoting his executive vice president of marketing and commercial development to the top job.
The focus has been on R&D up until this point, but in the next few years the biotech hopes approvals will come for elafibranor, and Pascal Prigent, with his experience on the marketing side, seems to dovetail with its potential future.
Prigent, who only joined last May and was formerly VP of marketing of GSK’s vaccines division, becomes the new chief in two weeks, and Mouney stays on as chair.

Loos, France-based Genfit is developing elafibranor for both nonalcoholic steatohepatitis (NASH), or fatty liver disease, and primary biliary cholangitis (PBC), an autoimmune disease of the liver.
Rival biotech Intercept Pharmaceuticals already markets a drug for this second rare condition, known as Ocaliva (and is also, along with seemingly almost every other biopharma, gunning for NASH), but Genfit is hopeful its attempt could be better.
A recent phase 2 linked the two tested elafibranor doses to 67% and 79% responses rates against the composite endpoint used in the pivotal Ocaliva trial. Ocaliva, meanwhile, came to market in PBC with a 47% response rate.

The bigger market opportunity is in NASH, which could yield billions annually for any company that gets it right, though nearly everyone in this area (and Genfit is one of the more advanced in terms of testing) has been hit by trial setbacks, Genfit included.
But sentiment has appeared to stay with the company; back in March, while already on the Euronext stock exchange, Genfit made the jump to the more lucrative Nasdaq with a healthy $135 million IPO.
Genfit earmarked $50 million of its IPO proceeds for the completion of its elafibranor program in NASH “through to, at least, the submission of an NDA to the FDA and EMA and the launch of a Phase 4 [postmarket] clinical trial,” it said in a recent SEC filing.
A readout of its late-stage data is expected later this year, the success of which, or lack thereof, will have a big impact on the biotech.
Mouney said in a release that his leaving is a “personal decision taken after thoughtful consideration, following two decades of intensive work dedicated to developing Genfit.”
He continued: “I’ve asked Pascal to accept the CEO position because I’m convinced he is best positioned to oversee our future corporate growth. Pascal has the right experience, the right skills, the right mindset and the right personality to help build Genfit for success in the years to come. I look forward to continuing my leadership as Chairman of the Board, including potentially recruiting new board members with international and diverse experience to best prepare us for the exciting years ahead.”
Prigent added: “I am honored to take on the role of Genfit’s CEO and look forward to working with Jean-François and the Board, as well as Dean and the highly skilled teams at Genfit. In the coming months, our Phase 3 RESOLVE-IT trial will have an interim read-out, and elafibranor could potentially become the first and only therapy to address NASH resolution without worsening of fibrosis. With our recent expansion into the United States and a solid cash position, we are preparing the company’s future as a commercial organization, to create long term value for our employees and shareholders, and for the NASH field overall, especially the patients.”
Analysts at ODDO put out a note to clients saying that while the timing may “cause confusion” with investors, it doesn’t believe the upcoming RESOLVE-IT data and the company’s CEO’s departure are linked.
“After a call with the company, we understand that this decision is unrelated to the future Phase 3 results of NASH (too early, results expected in Q4) and that this is a “personal decision taken with a great deal of objectivity and composure. … Our takeaway after contacting the company following this announcement is that the reorganization does not entail any changes to the group’s strategy. The teams and the targets will remain the same. The choice of Pascal Prigent makes sense in our view given his commercial experience and the fact that the company is potentially just some months from its commercial phase.
“Although the timing might cause some confusion with key clinical results for the group due out at the end of this year, there is no connection.”
Posted by at No comments:

Temple scientists identify promising new target to combat Alzheimer’s disease

Sometimes the more a person tries to fix a seemingly minor problem, the worse things become. Cells are no different, it turns out, though attempting to compensate for what begins as a minor deficiency or dysfunction can be dire. In the case of Alzheimer’s disease, Lewis Katz School of Medicine at Temple University (LKSOM) researchers now show that mitochondrial calcium transport remodeling – what appears to be an attempt by cells to compensate for flagging energy production and metabolic dysfunction – while initially beneficial, ultimately becomes maladaptive, fueling declines in mitochondrial function, memory, and learning.
The new research, published online in the journal Nature Communications, is the first to link maladaptive changes in calcium transport by mitochondria – the energy-generating powerhouses of cells – to the progression of Alzheimer’s disease.
“Amyloid-beta deposition and tau pathology are considered the major contributors to Alzheimer’s disease and, as a result, they have been the main focus of therapeutic development,” explained John W. Elrod, PhD, Associate Professor in the Center for Translational Medicine at LKSOM and senior investigator on the new study. “Large clinical trials targeting these pathways have universally failed, however.”
Altered calcium regulation and metabolic dysfunction have been suspected of contributing to neuronal dysfunction and Alzheimer’s development. “But up to now, no one has investigated the impact of altered calcium transport into and out of the mitochondria on the progression of Alzheimer’s disease,” Dr. Elrod noted. “Our current study provides a missing link between these two hypotheses of Alzheimer’s pathogenesis.”
Calcium transport into mitochondria plays an important part in many cellular functions and requires the involvement of multiple proteins to be carried out effectively. Among the key regulators of this process is a protein known as NCLX, which previously was discovered by Dr. Elrod’s laboratory to mediate calcium efflux from heart cells. NCLX expression is also important in mitochondrial calcium efflux in neurons.
In their new study, Dr. Elrod and colleagues examined the role of mitochondrial calcium uptake by neurons in Alzheimer’s disease. To do so, the team used a mouse model of familial Alzheimer’s disease in which animals harbored three gene mutations that give rise to age-progressive pathology comparable to Alzheimer’s progression in human patients.
As mice carrying the three mutations aged, the researchers observed a steady reduction in NCLX expression. This reduction was accompanied by decreases in the expression of proteins that limit mitochondrial calcium uptake, resulting in damaging calcium overload. NCLX loss was further linked to increases in the production of cell-damaging oxidants.
To better understand the physiological relevance of NCLX loss, Dr. Elrod’s team next completely eliminated NCLX expression in the forebrain of Alzheimer’s disease mice. In tests for memory and cognitive function, the animals exhibited significant impairments. Analyses of brain tissue from these mice showed that NCLX reduction and the consequent loss of calcium efflux from mitochondria accelerated the development of amyloid beta and tau pathology. When NCLX expression was restored, levels of harmful protein aggregates declined, neuronal mitochondrial calcium homeostasis was reestablished, and mice were rescued from cognitive decline.
“Our findings indicate that maladaptive remodeling of pathways to compensate for abnormalities in calcium regulation, which perhaps are meant to maintain energy production in cells, lead to neuronal dysfunction and Alzheimer’s pathology,” Dr. Elrod said. “Moreover, our data suggest that amyloid beta and tau pathology actually lie downstream of mitochondrial dysfunction in the progression of Alzheimer’s disease, which opens up a new therapeutic angle.”
Dr. Elrod and colleagues plan next to carry out a more detailed investigation of metabolic dysfunction that arises before Alzheimer’s disease pathology emerges.
###
Other investigators contributing to the new study include lead author, Pooja Jadiya, and co-authors Devin W. Kolmetzky, Dhanendra Tomar, Alyssa A. Lombardi, Jonathan P. Lambert, and Timothy S. Luongo, the Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine at Temple University; Antonio Di Meco and Domenico Pratico?, the Center for Translational Medicine and the Alzheimer’s Center at Temple, Lewis Katz School of Medicine at Temple University; and Marthe H. Ludtmann of the Royal Veterinary College, Kings Cross, London.
The research was supported in part by National Institutes of Health grants R01HL136954, R01HL123966, 3R01HL123966- 05S1, and R01HL142271 and by Pennsylvania Department of Health CURE Award 420792.
Posted by at No comments:

Scientists link ‘hunger hormone’ to memory in Alzheimer’s study

IMAGE
IMAGE: FROM BOTTOM LEFT: UNIVERSITY OF TEXAS AT DALLAS RESEARCHERS JING TIAN, A DOCTORAL STUDENT IN MOLECULAR AND CELL BIOLOGY, DR. LAN GUO, RESEARCH ASSISTANT PROFESSOR OF BIOLOGICAL SCIENCES, AND DR…. view more 
CREDIT: UNIVERSITY OF TEXAS AT DALLAS
Scientists at The University of Texas at Dallas have found evidence suggesting that resistance to the “hunger hormone” ghrelin in the brain is linked to the cognitive impairments and memory loss associated with Alzheimer’s disease (AD).
The findings, based on observations of postmortem brain-tissue samples from Alzheimer’s patients and on experiments with a mouse model of AD, also suggest a possible treatment strategy for the incurable neurodegenerative disorder that affects about 5.8 million older adults in the United States.
The research was published Aug. 14 as the cover article in the journal Science Translational Medicine.
“This is a proof-of-concept study, but we are very encouraged by the results,” said Dr. Heng Du, associate professor of biological sciences at UT Dallas and corresponding author of the study.
Produced in the stomach, ghrelin sends signals to the brain that regulate energy balance and body weight. Often called the hunger hormone, it plays a role in appetite and meal initiation. But ghrelin also has been implicated in learning and memory.
The hippocampus region of the brain — crucial to learning, memory and emotions — is one of the first to suffer cell death and damage in Alzheimer’s disease due to a toxic buildup of protein fragments called amyloid beta.
In a healthy hippocampus, ghrelin binds with proteins called ghrelin receptors, which combine with similarly activated receptors for the neurotransmitter dopamine. The two receptors then form a protein complex that helps maintain communication between brain cells and, ultimately, memory.
In the new study, Du and his colleagues found that amyloid beta binds to ghrelin receptors in the hippocampus, blocking their ability to combine with dopamine receptors.
“Our hypothesis is that this dissociation between ghrelin and dopamine receptors may be what is affecting cognition in Alzheimer’s patients,” Du said. “As the brain loses the function of ghrelin receptors due to amyloid beta, the body tries to compensate by increasing the production of ghrelin and the number of ghrelin receptors. But the amyloid prevents the receptors from functioning.”
Du likened the condition to insulin resistance found in individuals with type 2 diabetes. In that disease, insulin receptors malfunction.
“To compensate, patients in the early stages of type 2 diabetes produce more insulin to bind insulin receptors,” Du said. “But they become insulin-resistant. No matter how much insulin your body produces, the insulin receptors are unable to activate the downstream biochemical reactions needed to transport glucose from blood into cells.
“Similarly, based on our findings, Alzheimer’s might be linked to ghrelin resistance.”
Du said the new findings help explain why a recent clinical trial of a compound called MK0677 — designed to activate ghrelin receptors in the brain — proved unable to slow the progression of Alzheimer’s.
To test a different approach in their mouse model of AD, Du’s team gave the mice MK0677 and another compound — SKF81297 to activate dopamine receptors — at the same time.
“When we gave these compounds simultaneously, we saw improved cognition and memory in the AD mice, and lesions in the hippocampus were reduced,” Du said. “Activating both receptors at the same time was key; it restored the receptors’ ability to form complexes. When this happens, we suspect the ghrelin receptor becomes protected and can no longer bind to amyloid beta.
“More research is needed, but targeting this mechanism might prove therapeutically useful.”
Du, who has filed for a patent on the approach, said the team’s findings suggest that Alzheimer’s might be more than just a brain disease.
“As we age, we tend to experience changes in metabolism. These affect the heart and the gastrointestinal system, but maybe they also are affecting the brain by altering the ghrelin receptor,” he said. “We know that even in the absence of dementia, many older people have memory problems, and this could be related to the dissociation between the receptors in the brain, even without the presence of amyloid.
“I’m starting to think of Alzheimer’s as a systemic disorder, and that we should pay more attention to the metabolic and hormonal path of the disease.”
###
Other UT Dallas researchers involved in the study were co-lead authors Jing Tian, doctoral student in molecular and cell biology, and Dr. Lan Guo, research assistant professor of biological sciences; Dr. Sven Kroener, associate professor of behavioral and brain sciences, and his doctoral students Christopher Driskill and Aarron Phensy; Esha Gauba, doctoral student in molecular and cell biology; and visiting scholars Dr. Shaomei Sui and Dr. Qi Wang.
Additional authors include Dr. Jeffrey Zigman, professor of internal medicine at UT Southwestern Medical Center, and Dr. Russell Swerdlow, director of the University of Kansas Alzheimer’s Disease Center and the University of Kansas Medical Center Neurodegenerative Disorders Program.
The research was funded by the National Institutes of Health and the Alzheimer’s Association.
Posted by at No comments:

Bellus aims for IPO cash as it squares off with giant Merck on rival drug

Fueled by a successful Phase I trial treating chronic cough and lured by the promise of taking their lead drug to other applications, Montreal-based Bellus Health is looking to make its debut on Nasdaq with a $60 million IPO.
The public offering could be a major boon to the small Canadian company as it looks to outpace pharma giant Merck in the race to bring a P2X3-blocking drug to market. Blocking the P2X3 receptor is a closely studied method for reducing disorders around hypersensitivity, including most prominently chronic cough.
Merck has already brought their version — Gefapixant, or MK-7264 — to Phase III trials for chronic cough treatment, with high hopes in creating a major new franchise program. But Bellus points out in the S-1 filing that in their Phase I trial for BLU-5937 they were able to produce positive results without the taste-altering side effects that have marred Merck’s trials. In Merck’s latest trial, over 70% of patients who received 50 mg experienced taste loss or alteration, compared to 5% of patients in Bellus’s. In July, Bellus began its Phase II trial for chronic cough, which affects 26 million Americans.
No effective treatment currently exists.
Bellus also touts their P2X3 inhibitor as potentially useful against other disorders related to hypersensitivity. In 2020 they will begin a Phase II trial on eczema. The atopic dermatitis field is crowded, but Bellus claims 40-50% of patients are dissatisfied with their treatment.
In June Baird analyst Brian Skorney noted that he viewed BLU-5937 as a differentiated asset, saying it “may over time prove to be the best-in-class P2X3 antagonist.”
Originally called Neurochem, the company was forced to restructure in 2008 after their bid to launch their Alzheimer’s drug failed in a large clinical study. They changed their name and began focusing on orphan drugs, although ALZ-801 was
licensed by Alzheon in 2013.
This will be the second major fundraiser in less than a year for Bellus, as it raised $35 million at $0.95 a share from an equity offering in December.
As of June 30, the company had $42.4 million cash on hand. Bellus hopes to eventually sell BLU-5937 at $300-$600 per patient, per month. Listed in Canada, the company’s shares were trading at $2.04.
Posted by at No comments:

DOJ Takes Down ‘Pill Mill’ Network for Millions of Opioid RXs

The US Department of Justice (DOJ) has charged 41 people in nine indictments for their alleged involvement in a network of “pill mills” that allegedly resulted in the diversion of roughly 23 million oxycodone, hydrocodone, and carisoprodol pills.
Those charged include medical providers, clinic owners and managers, pharmacists, and pharmacy owners and managers, as well as drug dealers and traffickers.
The DOJ “continues to relentlessly pursue criminals, including medical professionals, who peddle opioids for profit,” Assistant Attorney General Brian Benczkowski, from the DOJ’s Criminal Division, said in a statement.
“This type of criminal activity is, in part, what is fueling the 68,500 overdose deaths per year across the United States,” Will Glaspy, special agent in charge of the Houston Division of the Drug Enforcement Administration (DEA), said in the statement.
“The DEA and our numerous law enforcement partners will not sit silently while drug dealers wearing lab coats conspire with street dealers to flood our communities with over 23 million dangerous and highly addictive pills,” Glaspy said.

Indictments in Texas and Massachusetts

The latest federal opioid enforcement actions were led by the Health Care Fraud Unit (HCF Unit) in the DOJ’s Criminal Division Fraud Section in conjunction with US Attorney’s Offices for the Southern and Eastern Districts of Texas and District of Massachusetts as well as the DEA and task force officers from greater Houston police departments and the Federal Bureau of Investigation.
The charges allege that participating doctors, medical professionals, and pharmacies knew the prescriptions had no legitimate medical purpose and were outside the usual course of professional practice, the DOJ said.
“They include a Houston-area doctor who, in less than 15 months, allegedly prescribed approximately 2 million pills of controlled substances — including over 800,000 oxycodone pills and almost 450,000 hydrocodone pills,” Benczkowski said August 28 during a Houston press conference.
“They also include the owner and pharmacist-in-charge at a pill mill pharmacy that has, in 2019, allegedly dispensed the second highest amount of oxycodone 30-mg pills of all pharmacies in the entire State of Texas, and the ninth highest amount in the nation. Amazingly, 100% of the oxycodone dispensed by this pharmacy — every single oxycodone pill that left the premises — was in the highest available dosage strength of that drug,” Benczkowski said.
The DOJ also announced that 350 law enforcement agents executed 36 search and seizure warrants in the Southern District of Texas, including 15 pharmacies and six “pill mill” clinics as well as other offices and residences, aimed at disrupting opioid diversion networks. And the DEA issued immediate suspension orders to nine DEA registrants, including seven pharmacies and two doctors, involved in dispensing controlled substances without legitimate medical purpose.
Benczkowski said he has a “message for those doctors, pharmacists, and other medical professionals engaging in this criminal behavior across the state of Texas and elsewhere in America: you may think you are invisible. But the data in our possession allows us to see you and see you clearly, no matter where you are. And if you behave like a drug dealer, we are going to find you, and treat you like a drug dealer.”
Posted by at No comments:

Cancer Overtakes Cardiovascular Disease as Lead Cause of Death in Rich Nations

Cancer is now the leading cause of death in high-income countries (HICs), where it is responsible for twice as many deaths as cardiovascular disease (CVD), according to findings from a new global report.
“The world is witnessing a new epidemiologic transition among the different categories of noncommunicable diseases, with CVD no longer the leading cause of death in HIC,” lead author Gilles Dagenais, MD, professor emeritus, Laval University, Quebec, Canada, said in a statement.
However, worldwide, CVD remains the leading cause of mortality.
CVD-related deaths were 2.5 times more common among middle-aged adults in low-income countries (LICs) than in HICs, although there was a substantially lower burden of CVD risk factors in these populations as compared with wealthier countries.
The study authors suggest that the higher CVD-related mortality observed in LICs may primarily be due to a lower quality of healthcare — first hospitalization rates and the use of CVD medication were lower in both LICs and middle-income countries (MICs).
“Our report found cancer to be the second most common cause of death globally in 2017, accounting for 26% of all deaths,” commented Dagenais.
“But as CVD rates continue to fall, cancer could likely become the leading cause of death worldwide within just a few decades,” he added.
The findings come from the Prospective Urban and Rural Epidemiologic (PURE) study, published online on September 3 in the Lancet.

Cancer Leading Cause in Wealthy Nations

The PURE study included 162,534 individuals aged 35 to 70 years who were living in 21 countries.
The HICs were Canada, Saudi Arabia, Sweden, and the United Arab Emirates.
The study did not include the United States, but previous research shows that cancer is now the leading cause of death, having surpassed CVD in about half of the states, and it is the leading cause of death in the Hispanic population, as reported by Medscape Medical News.
The MICs were Argentina, Brazil, Chile, China, Columbia, Iran, Malaysia, Palestine, Philippines, Poland, Turkey, and South Africa.
The LICs were Bangladesh, India, Pakistan, Tanzania, and Zimbabwe.
Median follow-up was 9.5 years. During that time, 9329 participants (5.7%) had CVD, 5151 (3.2%) had cancer, 4386 (2,7%) sustained injuries requiring hospital admission, 2911 (1.8%) developed pneumonia, and 1830 (1.1%) had chronic obstructive pulmonary disease (COPD).
Incident cancers, injuries, COPD, and pneumonia were most common among persons residing in HICs and were least common in LICs. This pattern was seen for breast, lung, colon, prostate, and gynecologic cancers.
The incidence of CVD per 1000 person-years was 7.1 in LICs, 6.8 in MICs, and 4.3 in LICs. Overall mortality rates were twice as high in LICs compared with MICs and were four times higher in LICs compared with HICs.
CVD and cancer were the most common causes of death overall, and there were marked differences by country income levels. In HICs, cancer mortality (1.7 deaths per 1000 person-years) was about 2.5 times more common than death from CVD (0.6 deaths per 1000 person-years). In MICs, it was 2.0 and 1.6 per 1000 person-years. In LICs, the difference was far more pronounced — the rate of deaths from CVD was three times higher than that from cancer (4.2 vs 1.4 deaths per 1000 person-years).
Thus, the ratio of deaths from CVD to those from cancer was 0.4 in HICs, 1.3 in MICs, and 3.0 in LICs.
These findings, note the authors, are consistent with those of the Global Burden of Disease Study (GBD), which found that cancer was the leading cause of death among adults aged 50 to 69 years in wealthy countries, whereas CVD was the leading cause of death in lower-income nations.

Modifiable CVD Risk Factors

In the companion article published in the Lancet, researchers investigated the relative contribution (population attributable factor [PAF]) of 14 modifiable risk factors to CVD in the PURE cohort.
The study included 155,722 community-dwelling, middle-aged individuals who did not have a prior history of CVD and who resided in the same 21 HICs, MICs, and LICs as in the PURE study.
Modifiable risk factors accounted for approximately 70% of cases of CVD and related death in the overall population. Metabolic factors were the predominant risk factors for CVD (41.2% of the PAF); of those, hypertensionaccounted for the greatest number (22.3% of the PAF).
Behavioral risk factors contributed to the most deaths (26.3% of the PAF), but the single largest risk factor was a low education level (12.5% of the PAF). Ambient air pollution was associated with 13.9% of the PAF for CVD.
There was a higher proportion of CVD and death in LICs than in MICs. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on CVD or mortality than in HICs.
Both studies have limitations, the authors caution. Although these are the only studies that have included as many as 21 countries, these results may not be generalizable to all countries.

Opportunities to Prevent Cancer and CVD

In an accompanying editorial directed to the second study on CVD risk factors, Stephanie H. Read, PhD, from Women’s College Hospital, Toronto, Ontario, Canada, and Sarah H. Wild, PhD, University of Edinburgh, United Kingdom, note that the current findings “can inform the effective use of limited resources — for example, by indicating the importance of improving education across the world and improving diet and reducing household air pollution in less developed countries.
“The value of collecting similar data to inform policy in a wider range of countries is clear, while improving lifestyle choices and modifying their social and commercial determinants remain a challenge,” they write.
In reference to the first study, Wild told Medscape Medical News that in HICs, heart disease and its related mortality “are becoming less common partly as a consequence of improvements in treatment, and because we all have to die of something, cancer is beginning to take over from cardiovascular disease as the most common cause of death.
“Cancer obviously comprises a variety of conditions, but some of the common cancers are related to unhealthy lifestyles, and there are clearly opportunities to prevent some cancers and also to improve treatments across the world,” she said.
The study was funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research (including through the Strategy for Patient-Oriented Research via the Ontario SPOR Support Unit), the Heart and Stroke Foundation (Ontario, Canada), the Ontario Ministry of Health and Long-Term Care, and by unrestricted grants from several pharmaceutical companies. It received major contributions from AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier Laboratories, and GlaxoSmithKline, and additional contributions from Novartis, King Pharma, and from several national and local organizations in participating countries. Several of the authors of both studies have disclosed relevant financial relationships, as noted in the original articles.
Lancet. Published online September 3, 2019. PURE study, Abstract; Companion article, Abstract; Editorial
Posted by at No comments:

Defibrillators Still Save Lives in Heart Failure

Implantable cardioverter-defibrillators (ICDs) continue to have a primary prevention survival benefit in the modern era of heart failure treatment but are still underused, a Swedish study suggested.
In the SwedeHF registry, just 10% of 16,702 patients eligible for a device under the European Society of Cardiology criteria for ICD prevention of sudden cardiac death in heart failure with reduced ejection fraction (HFrEF) actually got one since 2010.
Benedikt Schrage, MD, of the University Heart Center Hamburg, Germany, reported the results here at the European Society of Cardiology meeting and simultaneously online in Circulation.
“Even if one accounts for patients who may have received an ICD during follow-up and the fact that SwedeHF only includes 54% of patients countrywide, this utilization rate is disappointingly low,” Sana Al-Khatib, MD, MHS, of Duke University Medical Center in Durham, North Carolina, and Fred Kusumoto, MD, of the Mayo Clinic in Jacksonville, Florida, wrote in an accompanying editorial.
In a propensity-matched analysis, ICD use was associated with 27% lower all-cause mortality risk at 1 year (12.7% vs 16.9%, P<0.01) and 12% lower such risk at 5 years (47.4% vs 49.5%, P=0.04).
No such difference was seen between groups in risk of hospitalization for renal failure, dialysis, chronic lower respiratory disease, flu and pneumonia, or rheumatoid arthritis as a negative control, which Al-Khatib and Kusumoto said “provides reassurance that worse outcomes in the no-ICD group are not explained by avoidance of ICD implantation in sicker patients.”
These findings affirm the 20% to 30% reduction in mortality seen in the MADIT II and SCD-HeFT trials that inaugurated primary prevention ICD use in heart failure 20 years ago, even though it has been questioned due to the falling sudden cardiac death rate in this population as drug therapy has improved, Schrage and colleagues noted in their paper released Sept. 3.
While the DANISH trial played into that anti-ICD argument by showing no survival benefit of primary prevention ICDs in non-ischemic dilated cardiomyopathy, the editorial noted that DANISH had a large crossover to cardiac resynchronization therapy and enrollment criteria for elevated natriuretic peptides that probably selected patients more likely to die from advanced heart failure than sudden cardiac death.
Results in SwedeHF were consistent across subgroups, including by ischemic heart diseaseetiology, sex, age, period of enrollment, and cardiac resynchronization therapy.
The message now is to get the word out to general practitioners, Schrage said at a press conference for the late-breaking clinical trial.
“I think there is a strong perception of complications of ICD uses and difficulties to implant and maintain the device,” he said. “We knew before that the use of ICDs in Sweden is low and we can only speculate about that, that the perception of complications in the general practitioner’s mind does not outweigh the benefit of ICDs. I think our message now needs to be that communication of [how] ICD use will reduce morality.”
He suggested that the rate of use is higher in the U.S. — about 60% in one registry.
However, Salim Yusuf, MD, DPhil, of McMaster University’s Population Health Research Institute in Hamilton, Ontario, cautioned that this might not be the best comparison.
“Worldwide, the use of ICDs is under 2%. Sweden is one of the wealthier countries of the world. Now you can say it ought to be higher, but don’t compare anything with the U.S., because U.S. rates are off the chart for anything expensive you can do,” he said from the panel at the press conference. “I don’t think you’re that far off.”
“Whenever you look at rates of use of complex therapies, like ICD, a number of factors have to be taken into account, not just an EF [ejection fraction] in heart failure but what comorbidities do people have, do they have renal failure, are they demented, have they had severe COPD [chronic obstructive pulmonary disease]. These are all factors clinicians take into account in the decision about using it and then patient preferences,” Yusuf added. “Just simply comparing numbers doesn’t tell you the complete picture.”
The study received funding from Boston Scientific and the EU/EFPIA Innovative Medicines Initiative.
Schrage and the editorialists disclosed no relevant relationships with industry.
Posted by at No comments:
Subscribe to: Posts (Atom)