Category Archives: Cardiology

Stroke prevention drugs may help reduce dementia risk for atrial fibrillation patients

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Patients with atrial fibrillation could reduce the risk of dementia by taking stroke prevention medications, according to recommendations published online in EP Europace, a European Society of Cardiology journal, and presented at EHRA 2018.

The international consensus document was also published in HeartRhythm, the official journal of the Heart Rhythm Society (HRS), and Journal of Arrhythmia, the official journal of the Japanese Heart Rhythm Society (JHRS) and the Asia Pacific Heart Rhythm Society (APHRS).

The expert consensus statement on arrhythmias and cognitive function was developed by the EHRA, a branch of the ESC; the HRS; the APHRS; and the Latin American Heart Rhythm Society (LAHRS).

Heart rhythm disorders (arrhythmias), as well as some procedures undertaken to treat them, can increase the risk of cognitive decline and dementia. The international consensus document was written for doctors specialising in arrhythmias and aims to raise awareness of the risks of cognitive impairment and dementia and how to reduce them.

The document states that atrial fibrillation is associated with a higher risk for cognitive impairment and dementia, even in the absence of apparent stroke. This may be because atrial fibrillation is linked with a more than two-fold risk of silent strokes. The accumulation of silent strokes and the associated brain injuries over time may contribute to cognitive impairment.

Stroke prevention with oral anticoagulant drugs is the main priority in the management of patients with atrial fibrillation. The consensus document says that oral anticoagulation may reduce the risk of dementia.

Adopting a healthy lifestyle may also reduce the risk of cognitive decline in patients with atrial fibrillation. This includes not smoking and preventing or controlling hypertension, obesity, diabetes, and sleep apnoea.

“Patients with atrial fibrillation may be able to reduce their risk of cognitive impairment and dementia by taking their oral anticoagulation medication and having a healthy lifestyle,” said Dr Nikolaos Dagres, lead author and consultant, Department of Electrophysiology, Heart Centre Leipzig, Germany.

The document also reviews the association between other arrhythmias and cognitive dysfunction, including post-cardiac arrest, in patients with cardiac implantable devices such as implantable cardioverter defibrillators (ICDs) and pacemakers, and ablation procedures.

Treatment of atrial fibrillation with catheter ablation can itself lead to silent strokes and cognitive impairment. To reduce the risk, physicians should follow recommendations for performing ablation and for the management of patients before and after the procedure.

The consensus document notes that physicians may suspect cognitive impairment if a patient’s appearance or behaviour changes — for example, if appointments are missed. Family members should be asked for collateral information. If suspicions are confirmed, the consensus document recommends tools to conduct an objective assessment of cognitive function.

The paper highlights gaps in knowledge and areas for further research. These include, for instance, how to identify atrial fibrillation patients at increased risk of cognitive impairment and dementia, the effect of rhythm control on cognitive function, and the impact of cardiac resynchronisation therapy (CRT) on cognitive function.


Summit Therapeutics to expand clinical trials after healthy interim results

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Summit Therapeutics will expand enrollment in its phase 2 clinical trials studying the effect of ezutromid treatment on Duchenne muscular dystrophy (DMD), the company said on Wednesday.

The PhaseOut DMD trial is a multi-centre, 48 week open-label clinical trial with 40 enrolled patients between the ages of five and ten who suffer from DMD which will be enhanced by the newly announced parallel running expansion.

David Roblin, chief operating and medical officer of Summit, said: “We are extremely grateful to the patients who participated in our Phase 1 clinical trials and contributed to ezutromid’s clinical advancement, but were not initially eligible to participate in our Phase 2 clinical trial. Accordingly, we are pleased to open this additional group in our Phase 2 and provide these patients with the opportunity to receive ezutromid treatment.”

Patients with DMD will be eligible for the expanded trial regardless of their age or ambulatory status.

DMD is a muscle wasting disease that affects approximately 50,000 men and boys in the developed world and is caused by genetic faults in the gene that codes dystrophin and thus preventing the healthy function of all muscles.

The orally administered small molecule drug is intended to modulate utrophin, a protein functionally and structurally similar to dystrophin, with the aim of slowing or even halting DMD.

Recently announced 24 week interim data from the trials demonstrated that compared to baseline, ezutromid significantly reduced muscle damage and muscle inflammation attributed to the disease.

“We expect the data collected from this additional group of patients will help expand our understanding of ezutromid’s safety and efficacy profile across a broader patient population,” said Roblin.

Ezutromid has been granted Fast Track designation and Rare Pediatric Disease designation by the US Food and Drug Administration (FDA) as well as orphan drug status which allows for additional regulatory support and a period of market exclusivity following approval.


NICE ‘considering’ evidence to cut treatment threshold for hypertension

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NICE is considering new evidence which led to drastically lowered hypertension thresholds in the US.

The clinical advisory body, which is currently reviewing UK hypertension guidelines with a view to updating them in August 2019, told Pulse the reviews were ‘asking the same questions’.

The new US guidelines, published by the American Heart Association, decreased the threshold for stage one hypertension from an average systolic blood pressure of 140 to 130 mmHg, and from ≥160 to ≥140 mmHg for stage two.

Researchers said the changes could mean an extra 14% of people were diagnosed with hypertension, which would bring the total number to 46% of the country’s population.

The change was prompted by the 2015 SPRINT study, which showed that by treating patients with a target blood pressure of 120 mmHg, rather than the 140 mmHg target, mortality and cardiovascular events were significantly reduced.

When asked whether the changes brought in the US would be considered in the updated UK guidelines, a NICE spokesperson said: ‘Yes, we are asking some of the same questions being considered in the US and in doing so will be considering some of the same evidence.’

Current NICE guidelines define stage one hypertension as an average blood pressure of 135/85 mmHg or higher, and stage two as 150/95 mmHg or higher. It states that doctors should ‘offer antihypertensive drug treatment to people of any age with stage two hypertension’.

If the UK were to follow the US example, many patients currently defined as having stage one and treated with lifestyle changes could be pushed into stage two and medicated.

But this comes as last year, a meta analysis of 24 studies found that the evidence for reducing blood pressure targets to below 140 mmHg in over-60s was inconsistent.

The paper said that although lowering the targets could be beneficial, they could also be linked with a higher medication burden and an increased risk of short-term issues, such as hypotension.

Cardiology expert Dr Chris Aden, a GP in Southampton, said: ‘It’s going to be challenging in terms of the numbers they’re suggesting.

‘I think it’s down to good clinical common sense in how we apply it, particularly in the elderly or more frail groups’.

RCGP chair Professor Helen Stokes-Lampard said: ‘Lowering the threshold for making the diagnosis of any condition is a significant decision, that will affect thousands, if not millions of patients, and must not be taken lightly.’

‘One concern GPs already have is overdiagnosis – where we are giving a label to a situation thereby medicalising it, and prescribing medications when the benefits to the individual patient may be very limited.

‘This can be harmful for patients both in terms of causing unnecessary anxiety, and in terms of taking medication that they might not need.’

Pulse revealed in 2016 that new evidence including the SPRINT trial had prompted NICE advisors to consider updating hypertension guidelinesfor the first time since they were published in 2011.

Hypertension guidelines in full

New US classification

Normal <120/80 mmHg

Elevated 120-129/<80 mmHg

Stage 1 hypertension 130-139/80-89 mmHg

Stage 2 hypertension ≥140/90 mmHg

Current NICE guideline

Stage 1 hypertension – Clinic blood pressure is 140/90 mmHg or higher and subsequent ambulatory blood pressure monitoring (ABPM) daytime average or home blood pressure monitoring (HBPM) average blood pressure is 135/85 mmHg or higher

Stage 2 hypertension – Clinic blood pressure is 160/100 mmHg or higher and subsequent ABPM daytime average or HBPM average blood pressure is 150/95 mmHg or higher

Severe hypertension – Clinic systolic blood pressure is 180 mmHg or higher or clinic diastolic blood pressure is 110 mmHg or higher


AI predicts heart attack risk factors from retinal scans

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Artificial Intelligence can be used to predict heart attack risk using retinal images, according to new research backed by Google.

The researchers trained deep learning algorithms on data from thousands of patients recorded in a massive UK study, which was used with retinal scans to produce a program that can identify risk factors from the scan information alone.

This predicted cardiovascular risk factors not previously thought to be quantifiable using retinal images: these included age, gender, smoking status, gender, systolic blood pressure and major adverse cardiac events.

Reporting results in the journal Nature Biomedical Engineering, the team used a dataset from the UK’s Biobank, a study where 500,000 were recruited between 2006 and 2010, and agreed to have certain health measurements recorded.

Health outcomes such as hospitalisation, mortality and cause of death were also logged. Smoking status was obtained via survey using a touchscreen interface in the research backed by Google and Verily, Alphabet’s healthcare subsidiary.

Participants were also asked to identify whether they are a current smoker, former smoker, or had never smoked, and blood pressure readings were also taken.

A further 67,725 had paired images of their retina fundus taken, along with a second group that was used to create a training dataset with known risk factors.

The researchers asked a neural network to make an output prediction based on the fundus image.

It was able to analyse images from the group with unknown risk factors, compare it with the training data set and after the process was repeated, was eventually able to predict cardiovascular risk factors from new images.

This is just the latest in a series of studies showing the potential of AI to predict healthcare outcomes, saving lives and reducing costs by ensuring patients receive timely and sometimes life-saving treatments.

Early last month, the government’s life sciences tsar, Sir John Bell, said that similar techniques could save the NHS billions.

A team at Oxford’s John Radcliffe Hospital is using AI to identify abnormalities in ECG read-outs that could be missed by the human eye, for instance.

The hope is that this system could be used in hospitals across the country to prevent unnecessary hospitalisations caused by false positives, and prevent heart attacks where at-risk patients are sent home because doctors have failed to spot problems.

Another AI system outperformed a panel of experts when asked to diagnose breast cancer based on stained tissue samples, in a separate study published in the Journal of the American Medical Association last month.


Watch for this antibiotic if you have heart disease, FDA says

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Clarithromycin can kill even years later, FDA says.

People with heart disease need to be careful about using the common antibiotic clarithromycin, the Food and Drug Administration said.

Heart disease patients who take the drug, sold under the brand name Biaxin, can die years later, the FDA said.

The FDA said it does not know how clarithromycin might cause heart problems or death, but it’s been warning about the problem since 2005. But a review of data 10 years later shows heart patients still have a higher risk of dying if they took the antibiotic for two weeks.

“FDA is advising caution before prescribing the antibiotic clarithromycin (Biaxin) to patients with heart disease because of a potential increased risk of heart problems or death that can occur years later,” the FDA said in a statement.

“Healthcare professionalsshould be aware of these significant risks and weigh the benefits and risks of clarithromycin before prescribing it to any patient, particularly in patients with heart disease and even for short periods, and consider using other available antibiotics,” it added.

“Advise patients with heart disease of the signs and symptoms of cardiovascular problems, regardless of the medical condition for which you are treating them with clarithromycin.”

Clarithromycin can be prescribed to treat infections of the skin, ears, sinuses and lungs. It’s also favored for treating Mycobacterium avium complex (MAC) infection, a type of lung infection that often affects people with human immunodeficiency virus (HIV).

Patients with heart disease need to make sure they tell doctors who may prescribe the antibiotic – especially if it’s not their regular doctor.

“Talk to them about the benefits and risks of clarithromycin and any alternative treatments,” the FDA said.

“Do not stop taking your heart disease medicine or antibiotic without first talking to your healthcare professionals. Doing so could be harmful without your health care professionals’ direct supervision,” it added.

“Seek medical attention immediately if you experience symptoms of a heart attack or stroke, such as chest pain, shortness of breath or trouble breathing, pain or weakness in one part or side of your body, or slurred speech.”


Psoriasis drug found to reduce aortic vascular inflammation

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An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

Researchers from the Perelman School of Medicine at the University of Pennsylvania, in collaboration with the National Heart, Lung, and Blood Institute, led a randomised, double-blind, placebo-controlled study and found patients who took the drug ustekinumab had a 19 percent improvement in aortic inflammation, as measured and confirmed by imaging, when compared to the placebo group. Dr Joel M. Gelfand, a Professor of Dermatology and Epidemiology at Penn and the study’s first author.

Ustekinumab, sold under the name Stelara, is approved by the US Food and Drug Administration to treat psoriasis, psoriatic arthritis, and Crohn’s Disease. Researchers wanted to know if the benefits of the drug go beyond clearing the skin.

“The type of inflammation we see in psoriasis is similar to what we see in atherosclerosis – a type of heart disease that involves the build-up of fats, cholesterol, and inflammatory cells in the artery walls,” Dr Gelfand said. “Since ustekinumab blocks the specific pathways involved in both skin and cardiovascular inflammation, we wanted to test whether it can improve aortic vascular inflammation.”

Psoriasis patients were randomly divided into two groups, with 21 patients in the placebo group and 22 patients receiving the treatment. The primary outcome was aortic inflammation, as measured by 18-FDG-PET/CT scans – an imaging technique that reveals inflammation in the aorta. The imaging was performed before treatment and at 12 weeks. The treatment group saw a 6.6 percent decrease in aortic inflammation, while the placebo group saw a 12 percent increase, meaning the drug is responsible for a 19 percent improvement relative to untreated patients. As expected, ustekinumab also resulted in a dramatic improvement in skin inflammation as well, with 77 percent of treated patients achieving a 75 percent or better improvement in psoriasis activity, compared to just 10.5 percent in the placebo group. Both findings were highly statistically significant (p?0.001).

The results are consistent with a previous, smaller uncontrolled trial of ustekinumab, but they are in direct contrast to two large trials using a different drug called adalimumab, which is sold as Humira.

“This is the first placebo-controlled trial of a biologic drug to show a benefit in aortic inflammation, a key marker of cardiovascular disease,” Dr Gelfand said. “The effect is similar to what we would expect if we put the patient on a statin.”

Dr Gelfand, who conducted the study in collaboration with Dr Nehal N. Mehta, Chief of the Section of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute, confirmed their results by having a second, separate lab independently evaluate imaging data.

“This study represents a promise that this treatment may reduce the risk of heart attack and stroke in the future. It’s an encouraging finding,” Dr Gelfand said.

The trial is ongoing, and Dr Gelfand says his team will evaluate these patients at a longer follow up to see if the effects are sustainable and if patients continue to improve.


Boehringer Ingelheim, TARGET PharmaSolutions Partner to Progress NASH Research

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TARGET PharmaSolutions announced that Boehringer Ingelheim International GmbH has entered into a multi-year strategic partnership for TARGET-NASH.

TARGET-NASH is a longitudinal observational study that evaluates patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). To date, TARGET-NASH has enrolled 2,423 patients at 55 sites. TARGET-NASH will enroll up to 15,000 patients over the coming years. TARGET-NASH is led by an academic steering committee chaired by Drs. Arun Sanyal, MD (Virginia Commonwealth University); Ken Cusi, MD (University of Florida), and Brent Tetri (St. Louis University).

“We are very excited to have Boehringer Ingelheim join TARGET-NASH as an industry partner. We have exceeded our enrollment targets to date, and we are providing valuable real-world data and insight on NASH patients that will have a significant impact on the scientific understanding of the natural history and treatment modalities for NASH,” Meg Powell, CEO of TARGET PharmaSolutions, said. “This data, combined with the TARGET-NASH biorepository and patient reported outcomes, will enable our collaborators to continue to increase their understanding of this growing disease.”

Boehringer Ingelheim has a broad patient centric research and development program in metabolic diseases, encompassing diabetes as well as its contributing factors and complications. NASH is one of the company’s key focus diseases in this therapy area with a high unmet medical need and no treatments currently available. Recently Boehringer Ingelheim has e.g. initiated a Phase II clinical trial program with its investigational NASH treatment BI 1467335. The limited information available regarding NASH epidemiology is complicating the development of new medications. TARGET-NASH has thus been initiated to provide an improved baseline against which to measure the impact of new therapies on medical co-morbidities, natural history, and hepatic, cardiovascular, and endocrine-associated outcomes ultimately enabling the development of better treatments for NASH patients.

The TARGET model organizes a community of stakeholders, including pharmaceutical manufacturers, key opinion leaders, regulatory agencies, investigators, and patient advocacy groups, around a specific disease to generate real world evidence about the natural history of the given disease, current treatment paradigm, and patient outcomes.


Merck axes cholesterol drug despite phase 3 success

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Merck & Co has said it will not file its cholesterol drug anacetrapib with regulators, saying that trial results are not good enough for clinical filings.

The news came in a brief statement, which followed a surprise success for anacetrapib in the large multi-billion dollar phase 3 REVEAL trial earlier this year.

Merck & Co was the last big pharma developing a drug from the CETP class, after companies including Pfizer, Eli Lilly and Roche all scrapped development programmes following safety or efficacy issues.

The news from Merck means that industry has effectively given up on a class of drugs that a decade ago looked like being the next big thing in cardiology.

CETP (cholesterol ester transfer protein) drugs are designed to reduce levels of “bad” LDL cholesterol and boost levels of “good” HDL cholesterol, to reduce likelihood of fatty plaques in arteries that can restrict blood flow and lead to heart attacks and strokes.

Merck said it had made the decision after reviewing the clinical profile of anacetrapib, including discussions with external experts.

While Merck’s official statement suggests the drug would not get past regulators, the speculation is that anaceptrib could gain FDA approval, but would be unlikely to find a market because of the marginal efficacy gains.

The drug met a primary endpoint by reducing major coronary events (coronary death, myocardial infarction, or coronary revascularisation) by 9%.

But REVEAL missed a secondary endpoint of major atherosclerotic events (myocardial infarction, coronary death, or presumed ischaemic stroke).

It is the second drug development programme scrapped by Merck & Co in recent weeks, after the company axed development of its hepatitis C medicines after deciding their market potential was too weak amid tough competition from the likes of Gilead and a dwindling patient population.

Roger Perlmutter, president of Merck Research Laboratories, said: ““We are deeply grateful to the researchers and patients who participated in the anacetrapib clinical development programme, and in particular the REVEAL outcomes study. Unfortunately, after comprehensive evaluation, we have concluded that the clinical profile for anacetrapib does not support regulatory filings.”

“During the past half-century, Merck has made numerous, important contributions to the treatment of cardiovascular disease. Our work in cardiovascular research continues.”

Merck now has one cardiovascular candidate left in phase 3: vericiguat, an oral soluble guanylate-cyclase (sGC) stimulator being studied as a new heart failure treatment.


MSD pulls plug on cholesterol drug anacetrapib

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MSD has decided to pull the plug on its late-stage cholesterol drug anacetrapib after a lacklustre performance in clinical trials.

The company said it would not file for approval of the investigational cholesteryl ester transfer protein (CETP) inhibitor on the back of a review of its clinical profile that included discussions with external experts.

“Unfortunately, after comprehensive evaluation, we have concluded that the clinical profile for anacetrapib does not support regulatory filings,” said Roger Perlmutter, president of Merck Research Laboratories.

Earlier this year the firm presented data from the 30,000 patient REVEAL trial showing that the drug cut the risk of major coronary events by nine percent versus placebo in patients with cardiovascular disease already taking LDL-C lowering therapy alongside atorvastatin.

Compared with placebo, the addition of anacetrapib further reduced the mean level of non-HDL cholesterol by 18 percent and increased HDL cholesterol level by 104 percent at the study midpoint.

The difference in the key secondary composite outcome of major atherosclerotic events (myocardial infarction, coronary death or presumed ischaemic stroke) did not reach statistical significance.

Anacetrapib works by inhibiting a protein called cholesterol ester transfer protein (CETP), which is designed to lift HDL – or good – cholesterol. However, the class of drugs has been hit with a series of high-profile failures because of safety issues and mediocre efficacy.


Mallinckrodt licenses inhaled xenon gas therapy development product

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Mallinckrodt has entered into a licensing agreement for development and commercialisation of NeuroproteXeon’s investigational, pharmaceutical-grade xenon gas for inhalation therapy being evaluated to improve survival and functional outcomes for patients resuscitated after a cardiac arrest.

If approved, xenon gas for inhalation will expand Mallinckrodt’s portfolio of hospital drug-device combination products providing therapies for critically ill patients.

Under the terms of the agreement, Mallinckrodt will pay $10 million upfront with cash on hand to reimburse NeuroproteXeon for certain product development costs. The company will also gain exclusive rights to commercialise the therapy, if approved, in the U.S., Canada, Japan and Australia.

Mallinckrodt will make additional payments of up to $25 million dependent on the achievement of clinical, regulatory and sales milestones as well as a tiered, net-sales-based royalty.

NeuroproteXeon will continue to be responsible for the cost of development and will manage the development of the product in collaboration with Mallinckrodt.

Rates of resuscitation following cardiac arrest have risen modestly over time, but physicians say they still are not as high as they could or should be. Even when patients are successfully resuscitated, their outcomes are frequently still not positive, and post-arrest care and management continues to be an area of very high unmet medical need.

Dr. Steve Romano, Executive Vice President and Chief Scientific Officer, said: “The Phase 3 xenon gas for inhalation registration trial that will begin in early 2018 is designed to confirm a potential clinical benefit associated with the positive biomarker outcome as demonstrated on magnetic resonance imaging scans of patients treated with hypothermia therapy plus xenon gas for inhalation that was seen in a Phase 2b study. Those results showed a measurable reduction in brain damage. The Phase 3 trial, being conducted under an FDA Special Protocol Agreement, or SPA, will seek to measure the clinical benefit of xenon gas for inhalation in terms of improved 30-day survival and improved functional outcomes.”