Efficacy and Safety Profile of Dabigatran Etexilate Compared with Enoxaparin in Primary Venous Thromboembolism Prevention after Total Knee or Hip Replacement Surgery in Patients Over 75 Years
Authors: Dahl Ola E , Kurth Andreas A , Rosencher Nadia , Schnee Janet , Clemens Andreas , Noack Herbert , Eriksson Bengt I 
Published: April 2020

The oral direct thrombin inhibitor, Dabigatran etexilate (Pradaxa®), was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. Two pivotal clinical trials studied doses of 220 mg once daily and 150 mg once daily compared with 40 mg enoxaparin. A post hoc pooled analysis was performed in elderly patients (&gt;75 years) since the elderly, naturally lose renal function with aging. The efficacy and safety of once daily 220 mg and 150 mg dabigatran etexilate were compared with 40 mg subcutaneous enoxaparin using pooled data from the RE-MODEL (Eriksson BI et al. J Thromb Haemost2007; 5: 2178–2185) and RE-NOVATE (Eriksson BI et al. Lancet2007; 370: 949–956) pivotal trials. The primary efficacy endpoint was total VTE and all cause mortality and the primary secondary efficacy endpoint was major VTE and VTE related mortality. The primary safety endpoint was bleeding events, which were blindly adjudicated and categorized as major bleeding events (MBE), including surgical site bleeds. Of the patients treated with 220 mg dabigatran etexilate (1825), 150 mg dabigatran etexilate (1866) and enoxaparin (1848), 883 patients (16%) were above the age of 75, 73% of the elderly were evaluable for the primary efficacy endpoint, 75% were evaluable for the secondary efficacy endpoint, and all elderly patients were evaluable for safety including bleeding. The incidence of total VTE and all cause mortality was 20.8%, 22.6%, and 27.2% respectively in the three groups. A similar trend was observed for the secondary endpoint major VTE and VTE related mortality, with a descriptive statistical significant lower event rate in the 220 mg group (see table). MBEs occurred in 11 of the 295 elderly receiving 220 mg dabigatran etexilate (3.7%), 4 of the 282 elderly receiving 150 mg dabigatran etexilate (1.4%) and in 9 of the 306 elderly taking enoxaparin (2.9%). Notably, 6 of the 11 MBE in the dabigatran 220 mg group and 2 of the 4 MBE in the 150 mg group started before first oral treatment. In conclusion, in elderly patients (&gt;75 years) undergoing hip or knee replacement surgery, oral 150 mg dabigatran etexilate exhibited favourable bleeding profile with no difference in efficacy compared to 40 mg enoxaparin. Because safety is of paramount importance in the elderly who are at risk of any complications, the 150 mg once daily of dabigatran etexilate dose is currently recommended for this group.

Table 1: Efficacy and bleeding endpoints in patients older than 75 years (p-value from Fisher’s exact test compared to Enoxaparin)

Event Dabigatran etexilate 220 mg qd Dabigatran etexilate 150 mg qd Enoxaparin 40 mg qd Total VTE and all cause mortality 20.8% (44/212) (CI 15.5%–26.8%) p=0.14 22.6% (49/217) (CI 17.2%–28.7%) p=0.32 27.2% (58/213) (CI 21.4%–33.7%) Major VTE and VTE related mortality 1.9% (4/216) (CI 0.5%–4.7%) p=0.045 4.5% (10/221) (CI 2.2%–8.2%) p=0.53 6.0% (13/218) (CI 3.2%–10.0%) MBE 3.7% (11/295) (CI 1.9%–6.6%) p=0.65 1.4% (4/282) (CI 0.4%–3.6%) p=0.27 2.9%% (9/306) (CI 1.4%–5.5%)