Groundbreaking results for new atrial fibrillation medication

A new anticoagulant agent is more effective and safer than warfarin in preventing stroke in atrial fibrillation (AF) patients. This is one finding of an extensive international clinical study, RE-LY, led by the Uppsala Clinical Research Center (UCR) at Uppsala University and Uppsala University Hospital.

The results of the RE-LY study, the largest-ever clinical trial relating to treatment of AF patients, were presented today at the European Society of Cardiology Congress in Barcelona. The findings were published simultaneously on the website of the New England Journal of Medicine. The study compared the efficacy of a new anticoagulant agent, dabigatran (150 mg x 2 or 110 mg x 2), with that of warfarin, the standard treatment for preventing stroke in AF patients. A total of 18,113 patients in 44 countries throughout the world participated in the study. The average treatment period was two years.

The results show dabigatran (150 mg x 2) to be more effective than warfarin and to reduce the risk of stroke by 34 per cent (p<0,001) without increasing the incidence of major bleeding complications. At the lower dosage (110 mg x 2), dabigatran equalled the effectiveness of warfarin while reducing the risk of major bleeding. At both dosages, the new drug also reduced the risk of intracranial bleeding by approximately 70 per cent (p<0,001) compared with warfarin. An increased survival rate was observed in connection with higher-dosage dabigatran treatment.

"The results of dabigatran in RE-LY exceeded all our expectations," says Professor Lars Wallentin of the Uppsala Clinical Research Center, who headed the study. "We now have an oral treatment that offers superior protection from stroke and bleedings without the need for routine monitoring."

"We as physicians are especially concerned about life-threatening or disabling bleeding with warfarin," says Dr. Jonas Oldgren, who coordinated the efforts of Swedish treatment centres participating in the study. "On top of the efficacy, dabigatran has shown equally impressive safety results, offering a wider safety margin."

Dabigatran etexilate is manufactured by Boehringer Ingelheim, which financed the study, which was jointly led by Professor Lars Wallentin of the Uppsala Clinical Research Center (UCR), Uppsala, Sweden, Professors Stuart Connolly and Salim Yusuf of the Population Health Research Institute (PHRI), Hamilton, Ontario, Canada and Professor Michael Ezekowitz of the Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, USA. Jonas Oldgren of UCR served as the Swedish national coordinator.


KEY FACTS

About RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy):
RE-LY involved an international, randomised phase III trial comprising 18,113 patients at more than 900 hospitals in 44 countries. Of these patients, 277 were treated in Sweden (21 at Uppsala University Hospital and 23 at UCR). The study examined whether dabigatran etexilate (at two dosages) is as effective as the well-controlled open-label warfarin (INR 2.0-3.0) in preventing stroke. AF patients with at least one additional risk factor for stroke (e.g., history of ischemic stroke, TIA or systemic embolism, left ventricular dysfunction, age over 75, age over 65 in conjunction with diabetes, history of coronary artery disease or high blood pressure) were enrolled in the study for two years and followed up for a minimum of one year. The study's primary outcome measures were incidence of stroke (including haemorrhagic stroke) and systemic embolism. Total mortality, incidence of stroke (including hemorrhagic stroke), systemic embolism, pulmonary embolism, acute myocardial infarction and vascular death (including death from bleeding) were also measured. Additional safety endpoints included major and minor bleeding events, intracranial bleeding, intracerebral haemorrhage, elevated liver enzyme or bilirubin levels and liver dysfunction.

About AF and stroke:
AF is the most common heart rhythm condition, affecting approximately 1 per cent of the population and 10 per cent of people over the age of 80. There are presently approximately 100,000 AF patients in Sweden, who run an increased risk of forming blood clots, which increase the risk of stroke by a factor of seven. Approximately 5,000 patients in Sweden suffer AF-related strokes each year. AF-related stroke tends to be severe, raising the likelihoods of death (20%) and disability (60%) and resulting in significant costs and burdens to healthcare systems. Preventive treatment with anticoagulant agents is accordingly standard for patients characterised by AF or increased stroke risk.

About anticoagulant treatment of AF patients:
Warfarin and other vitamin-K antagonists function well with patients whose INR (a measure of coagulation) values remain within the narrow 2.0-3.0 interval, which can be ensured in the context of a clinical study such as RE-LY. Problems associated with warfarin entail that the medication is in fact prescribed to only 51 per cent of AF patients characterised by risk of stroke. Approximately 30 per cent of patients treated with warfarin exhibit INR values outside the therapeutic interval despite regular monitoring. Dabigatran belongs to a new generation of anticoagulant agents, direct thrombin inhibitors, which are useful in preventing and treating acute and chronic thromboembolic (blood-clot) conditions. The drug has been approved in more than 40 countries for prevention of ventral thromboembolic events in connection with hip- and knee-replacement surgery. Standard dabigatran treatment, unlike warfarin treatment, is associated with predictable anticoagulant effects. Moreover, the risk of interactions with food and medications is low, and routine INR monitoring and dosage adjustment is unnecessary.

Contact:
Lars Wallentin, Professor of Cardiology, Uppsala Clinical Research Center, mobile: +46-70-631 35 66 (currently in Barcelona)or Lars.Wallentin@ucr.uu.se

Please note that interviews with Professor Wallentin should be scheduled through Executive Assistant Anita Öström by calling +46-18-611 95 04 or (mobile) +46-70-296 04 40

Chief Physician Jonas Oldgren, cardiologist, mobile: +46-70-221 12 43 (currently in Barcelona)