Study shows ability of new agent to prevent strokes in patients with atrial fibrillation

August 10, 2011, Duke University Medical Center

In the primary result from the largest double-blind study ever completed to assess a drug's effect in the prevention of stroke in patients with atrial fibrillation, a common heart rhythm abnormality, rivaroxaban, an anti-clotting drug, was shown to be an attractive alternative to warfarin, the current standard for treatment of atrial fibrillation.

The full intention-to-treat analysis, which includes patients who discontinued study drug, showed that rivaroxaban was noninferior to warfarin for the prevention of stroke or blood clots. Importantly, rivaroxaban use led to less intra-cranial and fatal bleeding.

The findings, co-authored by a research team from the Duke Clinical Research Institute, were published online today in the New England Journal of Medicine.

"Warfarin has been a standard treatment for decades, but requires a rigorous monitoring schedule to ensure therapeutic dosing levels, and is subject to the potential of food and drug interactions that present treatment obstacles for patients and doctors alike," said the study's lead author, Manesh R. Patel, MD assistant professor of medicine at Duke University School of Medicine.

"The results of this large global trial have convincingly shown rivaroxaban to be an alternative to warfarin in treating patients with atrial fibrillation and, importantly, with no increase in bleeding."

Atrial fibrillation is the most common abnormal heart rhythm disorder in the U.S. and is characterized by an unusual and dangerously fast heart beat. It can cause blood to pool in the heart resulting in the formation of clots that may become lodged in the artery to the brain resulting in a stroke, or in formation of non-central nervous system blood clots.

Approximately 2.2 million Americans suffer from atrial fibrillation, which increases a person's stroke risk by four to six times on average.

Warfarin has been documented over the years to reduce the rate of stroke for those who have atrial fibrillation by approximately one-half to two-thirds, at the cost of increased bleeding.

"In addition to addressing an important therapeutic need for patients with atrial fibrillation, ROCKET AF provides a model for how clinical trials of investigational therapies should be conducted to assess safety and efficacy prior to FDA submission," said Robert M. Califf, MD, the study's co-chair, who is vice chancellor for clinical research at Duke University School of Medicine, and director of the Duke Translational Medicine Institute.

"The sponsors of the study should be congratulated for taking this approach in which an international committee of leaders in the field designed the trial and provided independent oversight, including an independent analysis of the trial results," Califf added.

The ROCKET AF (Rivaroxaban once daily oral direct factor xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) study included 14,264 patients with atrial fibrillation who had a history of stroke or additional independent risk factors for future stroke and were randomized to receive either rivaroxaban or warfarin. The trial included more than 1,100 centers in 45 countries.

In the analysis of the intent to treat population -- patients followed from the time of entry and throughout the full study duration, even if they discontinued study medication -- rivaroxaban was not inferior to warfarin (p< 0.001) and showed a nonsignificant trend toward benefit compared to warfarin (event rates = 2.12 vs. 2.42).

Rates of bleeding and adverse events were similar between treatment groups. Compared to warfarin, rivaroxaban showed similar rates for the principal safety measure of major and non-major clinically relevant bleeding events (event rates = 14.9 vs. 14.5, p=0.442). Rates of major bleeding were also comparable between rivaroxaban and warfarin (event rates = 3.6 vs. 3.4, p=0.576).

Patients treated with rivaroxaban had significantly fewer intracranial hemorrhages (event rates = 0.4 vs. 0.7), critical organ bleeds (event rates = 0.8 vs. 1.2) and bleeding-related deaths (event rates = 0.2 vs. 0.5) compared with warfarin, respectively. However, patients treated with rivaroxaban did show increased rates of hemoglobin/hematocrit drop (event rates = 2.8 vs. 2.3) and transfusions (event rates = 1.7 vs. 1.3), compared to warfarin.

"Atrial fibrillation is becoming increasingly prevalent and can be life-threatening if not properly managed. Stroke prevention is a key treatment goal in atrial fibrillation management," said Keith A. A. Fox, MB ChB, professor of cardiology at the University and Royal Infirmary of Edinburgh, Centre for Cardiovascular Science, in Edinburgh, UK, and one of the study's co-leaders "Rivaroxaban appears to be an attractive and well-tolerated clinical alternative to warfarin for patients with atrial fibrillation."

Explore further: J&J wins US approval for new blood thinner

Related Stories

J&J wins US approval for new blood thinner

July 2, 2011
(AP) -- Johnson & Johnson said Friday that U.S. regulators have approved its new type of blood thinner shown to reduce deadly blood clots in patients who have undergone knee and hip replacements.

Recommended for you

Researchers borrow from AIDS playbook to tackle rheumatic heart disease

January 22, 2018
Billions of US taxpayer dollars have been invested in Africa over the past 15 years to improve care for millions suffering from the HIV/AIDS epidemic; yet health systems on the continent continue to struggle. What if the ...

A nanoparticle inhalant for treating heart disease

January 18, 2018
A team of researchers from Italy and Germany has developed a nanoparticle inhalant for treating people suffering from heart disease. In their paper published in the journal Science Translational Medicine, the group describes ...

Starting periods before age of 12 linked to heightened risk of heart disease and stroke

January 15, 2018
Starting periods early—before the age of 12—is linked to a heightened risk of heart disease and stroke in later life, suggests an analysis of data from the UK Biobank study, published online in the journal Heart.

'Decorated' stem cells could offer targeted heart repair

January 10, 2018
Although cardiac stem cell therapy is a promising treatment for heart attack patients, directing the cells to the site of an injury - and getting them to stay there - remains challenging. In a new pilot study using an animal ...

Two simple tests could help to pinpoint cause of stroke

January 10, 2018
Detecting the cause of the deadliest form of stroke could be improved by a simple blood test added alongside a routine brain scan, research suggests.

Exercise is good for the heart, high blood pressure is bad—researchers find out why

January 10, 2018
When the heart is put under stress during exercise, it is considered healthy. Yet stress due to high blood pressure is bad for the heart. Why? And is this always the case? Researchers of the German Centre for Cardiovascular ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.