Dabigatran etexilate, a new oral direct thrombin inhibitor, for stroke prevention in patients with atrial fibrillation

Figures & data

Figure 1. Targets for new anticoagulants in the coagulation pathway.

Box 1. Drug summary.

Drug name (generic)	Dabigatran etexilate
Phase	II – III
Indication	Atrial fibrillation
Pharmacology description/ mechanism of action	Direct thrombin inhibitor
Route of administration	Oral
Chemical structure
Pivotal trial(s)	PETRO RE-LY

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Figure 2. Chemical structure of dabigatran (BIBR 953).

Table 1. Summary of clinical trials evaluating the role of dabigatran etexilate in atrial fibrillation.

Trial	No. of patients	Study type	Intervention	Comparison	Follow-up period	Comments
PETRO [31]	502	Phase II	50, 150 or 300 mg dabigatran twice daily alone or in combination with 81 or 325 mg aspirin	Warfarin administered to achieve an international normalized ratio between 2 – 3	12 weeks	Major bleeding events were observed in patients treated with dabigatran 300 mg plus aspirin, and thromboembolic episodes were observed in the 50 mg dabigatran groups. The two highest doses of dabigatran suppress D-dimer concentrations Serious hepatoxicity was not seen
RE-LY [32]	18,113	Phase III	Dabigatran 110 or 150 mg twice daily	Warfarin administered to achieve an international normalized ratio of 2-3	2 years	Compared with warfarin, dabigatran 110 mg twice daily was associated with similar rates of stroke and systemic embolism but lower rates of major hemorrhages. By contrast, dabigatran 150 mg twice daily was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage (in patients with atrial fibrillation)

PETRO: Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation; RE-LY: Randomized evaluation of long-term anticoagulation therapy.

Table 2. Major efficacy and safety outcomes in RE-LY [32].

Events	Dabigatran 110 mg (n = 6015) (%)	Dabigatran 150 mg (n = 6076) (%)	Warfarin (n = 6022) (%)
Stroke or systemic embolization	182 (1.53)	134 (1.11)	199 (1.69)
Major bleeding	322 (2.71)	375 (3.11)	397 (3.36)
Major or minor bleeding	1740 (14.62)	1977 (16.42)	2142 (18.15)
Life threatening bleeding	145 (1.22)	175 (1.45)	212 (1.80)
Intracranial bleeding	27 (0.23)	36 (0.30)	87 (0.74)
Extracranial bleeding	299 (2.51)	342 (2.84)	315 (2.67)
Myocardial infarction	86 (0.72)	89 (0.74)	63 (0.53)
Deaths	446 (3.75)	438 (3.64)	487 (4.13)

Ezekowitz MD, Reilly PA, Nehmiz G, Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419-26

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