Gale Scott

Patients with atrial fibrillation (AFib) have an increased risk of death when they take digoxin, a risk that increases with dosage, a study found.

In research presented at the ACC Scientific Sessions, Renato Lopes, MD, PhD, a professor of medicine in the division of cardiology at Duke University, said digoxin should no longer be considered a first-line drug for these patients.

“Digoxin should be avoided in patients with atrial fibrillation, particularly if their symptoms can be managed with other drugs,” he said.

The recommendation holds whether or not these patients have heart failure, he said.

Lopes and colleagues looked at a subset of patients from the ARISTOTLE trial, which compared apixaban with warfarin for anticoagulation.

Of 18,201 patients in ARISTOTLE, 17,897 had medical records that included their heart failure status and whether they were taking digoxin.

Of 5824 taking digoxin at the start of the trial, 4434 had baseline digoxin measurements.

A total of 6693 patients had heart failure at the time of trial enrollment.

The team found that in patients already taking digoxin—and thus more likely to tolerate it&mdash;there did not appear to be an increase in deaths. But even in this cohort, there was an increased risk related to taking a higher dose.

“Initiating digoxin in these patients had higher mortality,” Lopes said at a news conference. “Starting digoxin increased their risk of sudden death 4-fold.”

For every 0.5 ng/ml increase in the blood level of digoxin, the risk of death rose by 19%.

Among patients whose digoxin levels were greater than 1.2 ng/ml, the death rate increased by 56%.

That strongly suggests a dose-response relationship, but since the patients had not been randomized, that could not be proven. It will take a randomized controlled trial to eliminate possible confounding factors, Lopes said.

“Until then our finding that digoxin may be causing more harm than good in patients with AFib is important,” he said, one likely to change clinical practice.

Asked whether all AFib patients already on digoxin should stop, he said it was a judgment call and advised taking measurements of blood levels more frequently, monthly not every 6 months.

Digoxin use is “discouraged” by current ACC guidelines written in 2014, panelists noted.

In other parts of the world, particularly in Latin America and Asia, it is still a first-line drug.

Even in Europe it still carries a class I recommendation, Lopes said.

“The region of the world is the most important factor in whether digoxin is prescribed,” he said, and  guidelines need to be revisited.

Articles

Patients with atrial fibrillation (AFib) have an increased risk of death when they take digoxin, a risk that increases with dosage, a study found.
 

Digoxin Linked to High Risk of Sudden Death in AFib

A synthetic version of high-density lipoprotein (HDL), known as “good” cholesterol, did not reduce plaque as hoped when injected into the arteries of patients who recently had a heart attack.

Reporting at the 66th Scientific Session of the American College of Cardiology (ACC), Stephen Nicholls, MBBS, PhD, director of research at the Vascular Research Centre at the South Australian Health and Medical Research Institute, said the phase 2 CARAT trial failed to meet its primary endpoint.

Discussing the findings at a news conference this weekend, Nicholls said he has not given up on HDL research, but added, "I feel like I come here every 3 months with negative results—I feel like I need a hug." 

The goal had been to change the volume of fatty deposits in a coronary artery previously shown to be at least 30% blocked, Nicholls said.

The product, called CER-001, is manufactured by Cerenis Therapeutics.

Researchers had hoped that mimicking the body’s natural defenses that HDL-C uses to clear LDL cholesterol from the arteries, they got reverse plaque in patients at risk of adverse cardiovascular events.

Studies have suggested that levels of HDL-C above 40 in men and above 50 in women may be protective.

The synthetic product might also reduce dangerously high low-density lipoprotein (LDL)—bad cholesterol&mdash;in patients with familial hypercholesterolemia. In the CARAT trial, researchers enrolled 301 patients with an average age of 60, of whom 80% were men. The enrollees had a recent heart attack and at least one coronary artery blocked by more than 30% with fatty deposits.

Participants got 10 weekly infusions of CER-100 or placebo.

At the end of the study, participants’ arteries were examined by ultrasound. The team also looked at plaque volume, cholesterol levels, and the safety and tolerability of CER-100.

But there was no significant difference in the reduction of these arterial deposits in the group administered CER-100 and those administered placebo.

“We are disappointed that low-dose CER-001 did not show a benefit,” Nicholls said.

At the news conference, he said "HDL is more complicated than LDL and we know very little about it," adding that several companies continue to research HDL therapies and that they should. 

The study sites were in the United States, Australia, Hungary, and the Netherlands. Patients with uncontrolled diabetes, extremely elevated triglycerides, heart failure, liver disease or kidney disease were excluded from the study.

Researchers sought to change the volume of fatty deposits in a coronary artery that was at least 30% blocked.

Synthetic Cholesterol Drug Disappoints in Trial

An experimental Merck vaccine is showing 100% effectiveness against the Ebola virus, according to results of a trial in Guinea published in 

The vaccine was tested on people in West Africa from March 23, 2015 through Jan. 20, 2016, and has not been approved by the US Food and Drug Administration or any other agency, but is considered so effective than an emergency stockpile of 300,000 doses has already been created should there be another outbreak, the 

 study, the vaccine, called rVSV-ZEBOV (Merck Sharp & Dohme) is a recombinant replication competent vesicular stomatitis virus-based vaccine that expresses a surface glycoprotein of the Zaire strain of Ebola virus.

It was tested in Guineas and Sierra Leone.  It was given in a single intramuscular dose administered in the deltoid muscle. The researchers vaccinated known contacts of people with newly diagnosed Ebola infection. Some were vaccinated immediately, some not for 21 days. In all, there were 2,151 people vaccinated.

"No cases of Ebola virus disease occurred 10 days or more after randomisation," the researchers wrote. 

Funding was provided by the WHO, UK Wellcome Trust, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development). 

1. Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). 

http://dx.doi.org/10.1016/S0140-6736(16)32621-6

The researchers vaccinated known contacts of people with newly diagnosed Ebola infection. Some were vaccinated immediately, some not for 21 days. In all, there were 2,151 people vaccinated.
 

New Ebola Vaccine: 100% Effective

The FDA has granted breakthrough therapy designation to a drug candidate for post-traumatic stress disorder (PTSD).  

Cyclobenzaprine HCl sublingual tablets, known as TNX-102 SL, is made by Tonix Pharmaceuticals. According to the drug company, the designation was granted on the basis of the phase 2 study AtEase, which enrolled subjects who have PTSD associated with their military service. The trial was a 12-week, randomized controlled study.

A phase 3 study will begin in the first quarter of 2017, the company said.

The evidence of the phase 2 trial showed the drug, "may demonstrate substantial improvement over existing therapies one or more clinically significant endpoints," the company 

An estimated 8 million people in the United States have episodes of PTSD, the company said.  

Current treatments are generally with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

Tonix Pharmaceuticals Holding Company is based in Manhattan.

Drug candidate can treat individuals who have PTSD associated with their military service. 

FDA Awards Breakthrough Status to Post Traumatic Stress Drug

Diabetics tend to spend more time in the hospital than people without the condition.

Once admitted, their diabetes puts them at increased risk of in-hospital complications. Good glycemic control means these patients are less likely to develop nosocomial infections or surgical wound infections. In a new study in 

, researchers report on a multi-center trial of sitagliptin (Januvia/Merck) in managing these patients when they are admitted to in patient care either for general medical problems or surgery.

They wanted to see if the more convenient sitagliptin tablets would be just as good as insulin, which is injected and more complicated and labor-intensive to deliver. Sitagliptin works because it inhibits dipeptidyl peptidase IV (DPP-IV) and that results in prolonged active incretin levels. These hormones regulate glucose homeostasis.

They increase insulin synthesis and decrease glucagon secretion from pancreatic alpha cells. In healthy people, incretin hormones are released by the intestine all day and levels increase after eating. Incretin hormones are rapidly inactivated by the DPP-IV enzyme. In 

 study, researchers compared the safety and efficacy of sitagliptin plus basal insulin with basal-bolus insulin regimen for these hospitalized patients. The study was done at five US centers.

It was a prospective, open-label, non-inferiority trial. The patients were being treated with diet or oral antidiabetic drugs or had a total daily insulin doses of 0-to-6 units per kg or less. There were randomly assigned to receive either Sitagliptin plus basal glargine once daily or a basal-bolus regimen with glargine once daily and rapid-acting insulin before meals. All other antidiabetic drugs were discontinued on admission.

In all, 277 patients were assigned to the two treatment groups.

“The mean daily blood glucose concentration in the sitagliptin-basal group was not inferior to that in the basal-bolus group, with the first having levels of 9-5 mmol/l and the second 9.4 mmol/l," the team reported.

Treatment failure occurred at similar rates as did hypoglycemia and acute kidney injury (5% in the sitagliptin group and 4% in the basal bolus group). The conclusion was that “treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labor-intensive basal-bolus insulin regimen, lead investigator Prof. Guillermo Umpierrez, Emory University School of Medicine, Atlanta, GA, and colleagues wrote in the article.

Sitagliptin (Januvia/Merck) helps manage diabetes patients admitted hospital for general medical problems or surgery. 

Sitagliptin Equivalent to Insulin in Hospitalized Diabetics

Could magnesium have a positive effect on health by reducing the risk of ailments, such as cardiovascular disease and type 2 diabetes, as well as all-cause mortality?

Although researchers have published ambivalent findings in studies on those topics, a research team from China set out to look at whether the dosing matters.

Xuexian Fang of the Department of Nutrition, Nutrition Discovery Innovation Center at the School of Medicine at Zhengzhou University and colleagues took a retrospective look at 40 prospective cohort studies, with more than 1 million participants in 9 countries. Their dose-response analysis showed that the amount of magnesium consumed was important.

“Magnesium plays an important role in maintaining human health,” the researchers wrote.

They concluded that 100-mg per day reduces stroke by 7%, heart failure by 22%, type 2 diabetes by 19% and all-cause mortality by 10%. There was no proven benefit for total cardiovascular disease, however.

Magnesium is found in green leafy vegetables. Spices, nuts, beans and cocoa are also rich sources.

Eating spinach is not enough, however, the team wrote. Spinach has about 24 gm of magnesium per cup. People would do just as well to eat chocolate, since there are about the same number of grams in a tablespoon of cocoa.

Even better, a cup of salted, roasted, oily mixed nuts has more than 307 grams of magnesium, although that amount also packs more than 800 calories. The authors believe that it is more efficient to take oral supplements, or even an intravenous magnesium infusion.

Their analysis showed that adult men need 350-mg per day and women need 300-mg per day.

“The daily requirement for magnesium is difficult to achieve through a single serving of any one food item,” they noted, so “consuming a wide variety of magnesium-rich food will help ensure adequate daily intake of magnesium.”

Magnesium has been found to improve insulin sensitivity and glucose control in both people with diabetes and non-diabetics, Fang wrote.

The mineral is found mostly in skeletal tissue and controls the function of many enzymes, including those that utilize or synthesize adenosine triphosphate (ATP) a nucleoside triphosphate, a small molecule used in cells as a coenzyme involved in cellular energy production and transfer.

A randomized clinical trial is needed to definitely establish whether the team's findings hold up, the authors wrote.

 and was funded by the National Natural Science Foundation of China and the Zhejiang Provincial Natural Science Foundation. Both fund both basic research and applied science projects.

A diet with foods rich in magnesium may reduce rates of cardiovascular disease, type 2 diabetes, and all-cause mortality.