Dabigatran for stroke prevention in atrial fibrillation: the RE-LY trial

Abstract

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation. Vitamin K antagonists such as warfarin reduce the risk of cardioembolic stroke by approximately two-thirds compared with no treatment, but are limited by their unpredictable anticoagulant effect and narrow therapeutic index. Warfarin therapy requires routine coagulation monitoring, which is inconvenient for patients and costly for the healthcare system. The limitations of the vitamin K agonists have spurred the development of new oral anticoagulants that selectively inhibit thrombin or factor Xa. The Randomized Evaluation of Long-Term Anticoagulation (RE-LY) trial of 18,113 patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke demonstrated that dabigatran etexilate given at a dose of 150 mg twice daily compared with warfarin, reduced the rate of stroke or systemic embolism by one-third with a similar rate of major bleeding, whereas dabigatran etexilate given at a dose of 110 mg twice daily compared with warfarin had a similar rate of stroke or systemic embolism and reduced the rate of major bleeding by one-fifth. Both doses of dabigatran etexilate reduced intracranial bleeding by approximately two-thirds compared with warfarin. Based on the results of the RE-LY trial, both the US FDA and Health Canada recently approved dabigatran etexilate for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Oral anticoagulants and clinical decision making for stroke prevention in non-valvular atrial fibrillation for nurse practitioners

“…Dabigatran etexilate is an oral prodrug that is rapidly converted by a serum esterase to dabigatran, a potent, direct, competitive inhibitor of thrombin (Connolly et al, 2009). It directly inhibits free and clot-bound thrombin therefore inhibiting clot formation as well as thrombus expansion (Paikin et al , 2011). It is dosed as 110mg or 150mg BID and it has a relatively short half-life of 8-1 Oh and 14-17h for single and multiple-dose administrations, respective!…”

“…It has a more predictable anticoagulant response than warfarin with fewer drug-drug interactions (Paikin et al, 2011). Dabigatran is mostly excreted unchanged by the kidneys (80%), and it has a bioavailability of 6.5 % (Khoo & Lip, 2010).…”

“…Most importantly is that in both cases, the number of events is very low , including fatalities due to any cause (4.13 % for warfarin; 3.75 % for dabigatran 110mg; and 3.64% for dabigatran 150mg). There was also an increased risk of dyspepsia in the dabigatran group, which may lead to drug discontinuation or noncompliance , and a reduction in effectiveness (Paikin et al, 2011). These are all important considerations for the NP and will be discussed in further detail in the section of clinical decision-making.…”

“…of dabigatran for stroke prevention in non-valvular AF: the randomized evaluation of longterm anticoagulant therapy warfarin , compared with dabigatran (RE-LY) trial (Connolly et al, 2009;Eikelboom et al, 2011;Ezekowitz et al, 2009). Even though the RE-LY trial was a large and well-designed phase III , multicenter, prospective, open-label, randomized trial with blinded evaluation of all outcomes, it is still the only phase III RCT available, it was open label and surrounded by controversies .…”

“…When analyzing the RE-LY data, one observes that the patient is at increased risk of an intracranial bleed with warfarin treatment (0 .76% vs 0.32% with dabigatran 150mg), but increased risk of GI bleed with dabigatran . The high concentrations of active drug in the colon could explain the increase in GI bleeding with the higher dose of dabigatran, due to an increased local antihemostatic effect (Paikin et al , 2011). Most importantly is that in both cases, the number of events is very low , including fatalities due to any cause (4.13 % for warfarin; 3.75 % for dabigatran 110mg; and 3.64% for dabigatran 150mg).…”