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. 