Abstract

Abstract 2269

Background:

In randomized, double-blind, phase III trials, dabigatran etexilate (DE) 220 mg once daily (qd) was as effective as enoxaparin 40 mg qd in preventing venous thromboembolism (VTE) following total hip or knee replacement (THR, TKR), with a favourable safety profile. As patient populations in clinical practice may differ from those in clinical trials, we conducted an international, observational, single-arm study to evaluate the safety and efficacy of DE in a real-world setting. A prespecified secondary objective was to generate epidemiological data on the incidence of co-morbidities and co-medications in TKR and THR patients treated with DE in a routine clinical setting. We present here these epidemiological results as well as the patient characteristics observed in phase III clinical trials of DE and historical population studies.

Methods:

Patients were recruited at 110 sites in 9 countries in the European Union. The protocol required that patients were aged ≥ 18 years, undergoing elective THR or TKR and eligible for DE 220 mg qd (first dose 110 mg 1–4 hours after surgery) according to the European label (≤ 75 years old with creatinine clearance [CrCL] > 50 mL/min). Baseline data were collected at the screening visit prior to surgery. In the phase III clinical trials of DE, randomization to DE 220 mg qd or 150 mg qd was irrespective of age and renal function.

Results:

Of the 5292 patients treated in this observational study, 2734 underwent THR and 2558 TKR. Table 1 shows the baseline demographics and medical history and the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA). Patients undergoing TKR were more often female and mean BMI was higher than THR patients. With the exception of diabetes, other co-morbidities and co-medications were comparable between TKR and THR patients.

Mean CrCL and mean age at baseline were influenced by the inclusion and exclusion criteria for the study and therefore differed from those in the Phase III DE trials (Table 2).

Regarding gender, BMI, diabetes and history of VTE, the data from the observational study are generally comparable to those found in other large observational studies (e.g., White, et al. Arch Intern Med. 1998;158:1525–1531; Andersen, et al. Chest. 2003;124:349–356; Warwick, et al. J Bone Joint Surg Br. 2007;89-B:799–807). The incidences of the primary endpoints for efficacy (symptomatic VTE and all-cause mortality) and safety (major bleeding events) in the observational study are reassuring and supportive of the evidence seen in the clinical trials.

Conclusions:

Demographic characteristics of the patients included in the observational study are broadly aligned with previously published real-world data sets and add detail on co-morbidities. Patients included in this observational study were in general similar to those of the phase III TKR and THR trials of DE but a valid direct comparison between these data should take into account the differences in age and renal function due to study design.

Table 1.

Baseline demographics, medical history and concomitant NSAID/ASA use in the observational study

TKRTHR
N 2734 2558 
Demographics 
Age, years, mean 64.6 60.8 
Male sex, % 36.7 47.3 
Race whitea, % 98.6 99.3 
BMI, kg/m2, mean 30.5 27.8 
CrCL, mL/min, mean 106.1 110.0 
Medical history 
Hypertension, % 56.6 42.2 
Diabetes mellitus, % 12.7 7.6 
Coronary artery disease, % 7.3 4.8 
History of VTE, % 4.4 2.7 
Concomitant medications 
NSAIDs, % 54.6 58.9 
ASA, % 9.9 6.1 
TKRTHR
N 2734 2558 
Demographics 
Age, years, mean 64.6 60.8 
Male sex, % 36.7 47.3 
Race whitea, % 98.6 99.3 
BMI, kg/m2, mean 30.5 27.8 
CrCL, mL/min, mean 106.1 110.0 
Medical history 
Hypertension, % 56.6 42.2 
Diabetes mellitus, % 12.7 7.6 
Coronary artery disease, % 7.3 4.8 
History of VTE, % 4.4 2.7 
Concomitant medications 
NSAIDs, % 54.6 58.9 
ASA, % 9.9 6.1 
a

Race was not reported for 1535 patients; percentages are based on patients with non-missing information.

Table 2.

Baseline demographics and medical history and concomitant NSAID/ASA use in the phase III clinical trials (DE 220 mg qd groups)

TKRTHR
RE-MODELRE-NOVATERE-NOVATE II
N 679 1146 1010 
Demographics 
Age, years, mean 67.3 64.6 61.9 
Male sex, % 35.1 44.5 46.4 
Race white, % 98.8 99.2 90.5 
BMI, kg/m2, mean 29.9 27.7 27.8 
CrCL, mL/min, mean 89.4 88.6 96.6 
Medical history 
Hypertension, % 59.8 46.6 45.2 
Diabetes mellitus, % 11.9 6.4 9.1 
Coronary artery disease, % 11.8 9.0 6.7 
History of VTE, % 3.7 3.5 2.5 
Concomitant medications 
NSAIDs, % 64.7 53.7 73.8 
ASA, % 3.4 3.9 6.8 
TKRTHR
RE-MODELRE-NOVATERE-NOVATE II
N 679 1146 1010 
Demographics 
Age, years, mean 67.3 64.6 61.9 
Male sex, % 35.1 44.5 46.4 
Race white, % 98.8 99.2 90.5 
BMI, kg/m2, mean 29.9 27.7 27.8 
CrCL, mL/min, mean 89.4 88.6 96.6 
Medical history 
Hypertension, % 59.8 46.6 45.2 
Diabetes mellitus, % 11.9 6.4 9.1 
Coronary artery disease, % 11.8 9.0 6.7 
History of VTE, % 3.7 3.5 2.5 
Concomitant medications 
NSAIDs, % 64.7 53.7 73.8 
ASA, % 3.4 3.9 6.8 
Disclosures:

Rosencher:Sanofi (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees; Pfizer (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees; BMS (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees; Bayer (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees; GSK (haemostasis, thrombosis and transfusion): Membership on an entity's Board of Directors or advisory committees. Frostick:Pfizer (anticoagulant therapy): Speakers Bureau; Bristol-Myers Squibb (anticoagulant therapy): Speakers Bureau; Biomet (product development and education): Speakers Bureau; Boehringer Ingelheim (anticoagulant therapy): Speakers Bureau; DePuy (product development and education): Consultancy; Boehringer Ingelheim (anticoagulant therapy): Consultancy; Biomet (product development and education): Consultancy; DePuy (product development and education): Research Funding; Johnson & Johnson (anticoagulant therapy): Research Funding. Feuring:Boehringer Ingelheim (anticoagulant therapy): Employment. Kleine:Boehringer Ingelheim (anticoagulant therapy): Employment. Brueckmann:Boehringer Ingelheim (anticoagulant therapy): Employment. Clemens:Boehringer Ingelheim (anticoagulant therapy): Employment. Samama:GSK (anticoagulant therapy): Primary Investigator Other; LFB (anticoagulant therapy): Primary Investigator, Primary Investigator Other; Fresenius: Membership on an entity's Board of Directors or advisory committees; Curacyte (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; Bayer (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; Baxter (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; Lilly (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; BMS (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; Pfizer (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; GSK (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis (anticoagulant therapy): Membership on an entity's Board of Directors or advisory committees; CSL Behring (anticoagulant therapy): Honoraria; Biotest (anticoagulant therapy): Honoraria; Bayer (anticoagulant therapy): Honoraria; Boehringer Ingelheim (anticoagulant therapy): Honoraria; LFB (anticoagulant therapy): Honoraria; Cordis (product development and education): Honoraria; Sanofi (anticoagulant therapy): Primary Investigator, Primary Investigator Other.

Author notes

*

Asterisk with author names denotes non-ASH members.