Dabigatran etexilate for thromboprophylaxis in over 5000 hip or knee replacement patients in a real-world clinical setting

Abstract

Background: Thromboprophylaxis is recommended for patients undergoing total hip or total knee replacement (THR, TKR). An international, open-label, prospective, observational, single-arm study in a routine clinical setting was performed to assess the safety and efficacy of dabigatran etexilate 220 mg once daily in patients undergoing THR or TKR, and in subgroups of patients with potentially increased risk of bleeding or venous thromboembolism (VTE).

Materials and methods: Patients were ≥18 years and required to be eligible to receive dabigatran 220 mg once daily (first dose 110 mg 1-4 h after THR/TKR surgery) according to the European Summary of Product Characteristics. The primary safety and efficacy outcomes were incidence of major bleeding events (MBEs), and the composite incidence of symptomatic VTE events and all-cause mortality, respectively.

Results: In total, 5292 patients (median age 64 years) were enrolled and received dabigatran (2734 THR and 2558 TKR). Median drug exposure was 31 days (THR 34 days; TKR 27 days). Overall incidence of MBEs was 0.72 % (95 % confidence interval [CI] 0.51, 0.98), and this rate was comparable between types of surgery and was not significantly affected by protocol-defined risk factors. The overall incidence of symptomatic VTE and all-cause mortality was 1.04 % (95 % CI 0.78, 1.35); the only significant risk factor was history of VTE events (odds ratio 5.59; 95 % CI 2.53, 11.08). A post-hoc analysis showed that the incidence of MBEs in this observational study was similar to or lower than those reported in previous phase 3 trials.

Conclusions: Results from this observational study of dabigatran etexilate administered to patients undergoing THR or TKR surgery are reassuring and supportive of those obtained in dabigatran phase 3 trials.

Trial registration: ClinicalTrials.gov identifier: NCT00846807.

Keywords: Dabigatran etexilate; Observational study; Thromboprophylaxis; Total hip replacement; Total knee replacement.

Figures

Fig. 1

Patient disposition flow diagram. Treated set included 64 noneligible patients. Eligibility to participate and reasons for discontinuation were noted by investigators by completion of tick boxes. SmPC Summary of Product Characteristics

Fig. 2

Effect of protocol-defined risk factors on the incidence of MBEs – odds ratios (95 % CI). Odds ratios, based on univariable logistic regression, were calculated for presence versus absence of risk factor; CIs and p values are based on likelihood-ratio statistics. ASA acetylsalicylic acid, CAD coronary artery disease, CHF chronic heart failure, CI confidence interval, MBE major bleeding event, NSAIDs non-steroidal anti-inflammatory drugs, VTE venous thromboembolism

Fig. 3

Cumulative incidence of MBEs over time from the start of treatment, treated set. No events occurred after day 29 in THR patients or day 14 in TKR patients. MBE major bleeding event, THR total hip replacement, TKR total knee replacement

Fig. 4

Effect of pre-specified risk factors on the incidence of sVTE and all-cause mortality, treated set. No events occurred in patients with CHF. Odds ratios, based on univariable logistic regression, were calculated for presence versus absence of risk factor; CIs and p values are based on likelihood-ratio statistics. ASA acetylsalicylic acid, CAD coronary artery disease, CHF chronic heart failure, CI confidence interval, NSAIDs non-steroidal anti-inflammatory drugs, sVTE symptomatic venous thromboembolism

Fig. 5

Cumulative incidence of sVTE or all-cause mortality over time from the start of treatment, treated set. No new events occurred after day 33 in THR patients or day 27 in TKR patients. sVTE symptomatic venous thromboembolism, THR total hip replacement, TKR total knee replacement