Edoxaban Effective in Preventing Stroke, Reducing Bleeding and Cardiovascular Death in Patients With Atrial Fibrillation
According to the United States Centers for Disease Control and Prevention, over 800,000 Americans die each year from heart disease and stroke. Stroke is the leading cause of serious long-term disability and death in the US. In addition to lifestyle changes, medications such as anti-blood clotting drugs are helpful in the prevention of stroke.
A late-breaking clinical trial to be presented at the American Heart Association Scientific Sessions on November 19, 2013 and published simultaneously online in The New England Journal of Medicine, demonstrates that high- and low-dose edoxaban were at least as effective in preventing stroke or systemic embolism (blood clot), while significantly reducing bleeding and cardiovascular death, compared to warfarin.
“Our study findings represent good news for patients and health care providers,” said Robert Giugliano, MD, SM, FACC, FAHA, BWH Cardiovascular Division, lead study author. “We believe that once-daily edoxaban represents a new, effective, safe and convenient treatment to prevent stroke for many patients with atrial fibrillation, with the benefits of less bleeding and cardiovascular death, compared to standard therapy with warfarin.”
Edoxaban and warfarin are anti-blood clotting medications. Edoxaban is a once-daily oral factor Xa inhibitor currently being studied in clinical trials. Warfarin is a common drug prescribed to prevent the formation of blood clots, and has been the standard oral blood thinner for over five decades.
Led by the TIMI (Thrombolysis In Myocardial Infarction) Study Group at Brigham and Women’s Hospital (BWH) and Harvard Medical School, the ENGAGE AF-TIMI 48 trial was the largest (21,105 participants) and longest (2.8 years average follow-up) trial of a novel anticoagulant to date in patients with atrial fibrillation. The study compared two dose-regimens of once-daily edoxaban versus warfarin.
Researchers recruited participants with atrial fibrillation (irregular heart rate) who were at moderate-to-high risk for stroke. The trial was conducted at 1,393 centers in 46 countries. Participants were enrolled from November 2008 to November 2010.
Prevent Stroke
Prevent stroke - the second single biggest killer and the leading cause of disability amongst adults in Australia
1 in 6 people will have a stroke - behind these numbers are real lives. Strokes can happen to anyone so it is important to know your stroke risk.
Stroke is not a heart attack. A stroke happens when the supply of blood to the brain is suddenly disrupted. Blood is carried to the brain by blood vessels called arteries.
Blood may stop moving through the artery because the artery is blocked by a clot or plaque, or because the artery breaks or burst. When blood stops flowing, the brain does not get the oxygen it needs, and so brain cells in the area die, and permanent damage can be done.
Some strokes are fatal while others cause permanent or temporary disability. It is important to understand that stroke can be prevented.
Patients had an equal chance to receive warfarin, high-dose edoxaban (60 milligrams/day), or low-dose edoxaban (30 milligrams/day), although knowledge of which treatment they were assigned was not revealed until after the end of the study.
About one-quarter of the patients had the dose of edoxaban lowered at the start of the trial based on their individual profile to ensure the desired blood level of the drug. To ensure patients treated with warfarin had the proper degree of blood-thinning, blood tests were performed at least monthly in each group, although such testing is not necessary with edoxaban.
The primary goals of the study were to assess the combined outcome of stroke or systemic embolism (primary efficacy outcome), as well as bleeding.
During the treatment period, the rate of stroke or systemic embolism was 1.50 percent per year for participants on warfarin, and 1.18 percent per year for those on high-dose edoxaban. This represents a 21 percent reduction in the risk of stroke or systemic embolism with high-dose edoxaban compared to warfarin.
Preventing stroke
The best way to prevent a stroke is to eat a healthy diet, exercise regularly and avoid smoking and excessive consumption of alcohol.
Diet
A poor diet is a major risk factor for a stroke. High-fat foods can lead to the build-up of fatty plaques in your arteries and being overweight can lead to high blood pressure.
A low-fat, high-fibre diet is recommended, including plenty of fresh fruit and vegetables (five portions a day) and whole grains. You should limit the amount of salt you eat to no more than 6g (0.2oz) a day because too much salt will increase your blood pressure. Six grams of salt is about one teaspoonful.
There are two types of fat - saturated and unsaturated. You should avoid food containing saturated fats because these will increase your cholesterol levels.
Foods high in saturated fat include:
meat pies
sausages and fatty cuts of meat
butter
ghee – a type of butter often used in Indian cooking
lard
cream
hard cheese
cakes and biscuits
foods that contain coconut or palm oil.
However, a balanced diet should include a small amount of unsaturated fat, which will help reduce your cholesterol levels.
Foods high in unsaturated fat include:
oily fish
avocados
nuts and seeds
sunflower, rapeseed, olive and vegetable oils
Moreover, annualized rates of major bleeding were 3.43 percent with warfarin and 2.75 percent with high-dose edoxaban, representing a 20 percent reduction in bleeding. There were also fewer cardiovascular deaths with edoxaban compared to warfarin: high-dose edoxaban 2.74 percent per year compared to warfarin 3.17 percent per year.
The favorable results with edoxaban were achieved despite excellent management with warfarin in this study (blood tests were in range more than two-thirds of the time, a higher rate than that seen in other similar studies).
Future research with edoxaban will investigate if patients with other conditions treated with warfarin might benefit from edoxaban. Additional research will also help doctors determine how to measure the blood-thinning effect of edoxaban and how to quickly reverse the effect if needed.
This research was supported by Daiichi Sankyo.
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Brigham and Women’s Hospital 2013