RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy)

• Background:

Dabigatran etexilate is one of several oral anticoagulants in clinical trials for the prevention of AF-related thromboembolism, venous thromboembolism, and other conditions for which warfarin had long been the only choice

• Population and treatment:

18 113 patients with AF (mean age 71) and at least one other risk factor for stroke

Randomized to blinded treatment with dabigatran 110 mg or 150 mg twice a day or unblinded prophylaxis with warfarin adjusted to an INR of 2.0–3.0

• Primary outcome:

Stroke/peripheral embolic events

MD Ezekowitz (Lankenau Institute for Medical Research, Wynnewood, PA)European Society of Cardiology 2009 Congress

Outcomea Dabigatran low dose (%)

Dabigatran high dose (%)

Warfarin (%)

Relative risk (95% CI) for low dose vs warfarin

p for low doseb

Relative risk (95% CI) for high dose vs warfarin

p for high doseb

Primary end point 1.53 1.11 1.69 0.91 (0.74–1.11) <0.001c 0.66 (0.53–0.82) <0.001

Mortality 3.75 3.64 4.13 0.91 (0.80–1.03) 0.13 0.88 (0.77–1.00) 0.051

MI 0.72 0.74 0.53 1.35 (0.98–1.87) 0.07 1.38 (1.00–1.91) 0.048

Hemorrhagic stroke 0.12 0.10 0.38 0.31 (0.17–0.56) <0.001 0.26 (0.14–0.49) <0.001

Major bleeding 2.71 3.11 3.36 0.80 (0.69–0.93) 0.003 0.93 (0.81–1.07) NS

Efficacy results at two years

• High-dose dabigatran reduced the annualized risk of the primary end point by 34% (p<0.001) and the risk of hemorrhagic stroke by 74% (p<0.001) vs warfarin

• High-dose dabigatran was associated with a slightly but significantly (p=0.048) increased risk of MI, a secondary end point

RE-LY: Results

a. Annualized ratesb. p values are for superiority unless otherwise indicated c. For noninferiority

RE-LY: Commentary*

*All comments from RE-LY: Oral antithrombin dabigatran outshines warfarin in atrial fib (http://www.theheart.org/article/995769.do)

"The effect of dabigatran in reducing stroke and intracerebral bleeds far outweighed the small increase in MI rate, but this is a question we will be looking into in much more detail."

- Dr Michael D Ezekowitz

"Dabigatran, I think will be the new gold standard."

- Dr Albert L Waldo

"An anticoagulant that actually is more effective than warfarin and doesn't have the side effect of increased bleeding? It's almost never happened before, it's remarkable."

- Dr Stuart J Connolly (first author)