Dabigatran and the Risk of Staphylococcus aureus Bacteremia: A Nationwide Cohort Study

2020 ◽  
Author(s):  
Jawad H Butt ◽  
Emil L Fosbøl ◽  
Peter Verhamme ◽  
Thomas A Gerds ◽  
Kasper Iversen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Staphylococcus Aureus ◽  
Incidence Rate ◽  
Factor Xa ◽  
Direct Thrombin Inhibitor ◽  
Factor Xa Inhibitors ◽  
Thrombin Inhibitor ◽  
Factor Xa Inhibitor ◽  
Lower Incidence Rate

Abstract Background Treatment with dabigatran, an oral direct thrombin inhibitor, reduces the virulence of Staphylococcus aureus in in vitro and in vivo models. However, it remains to be determined whether dabigatran reduces the risk of S. aureus infections in humans. We investigated the incidence rate of S. aureus bacteremia (SAB) in patients with atrial fibrillation treated with the direct thrombin inhibitor dabigatran compared with patients treated with the factor Xa-inhibitors rivaroxaban, apixaban, and edoxaban. Methods In this observational cohort study, 112 537 patients with atrial fibrillation who initiated treatment with direct oral anticoagulants (August 2011–December 2017) were identified from Danish nationwide registries. The incidence rates of SAB in patients treated with dabigatran versus patients treated with the factor Xa-inhibitors were examined by multivariable Cox regression accounting for time-dynamic changes in exposure status during follow-up. Results A total of 112 537 patients were included. During a median follow-up of 2.0 years, 186 patients in the dabigatran group and 356 patients in the factor Xa-inhibitor group were admitted with SAB. The crude incidence rate of SAB was lower in the dabigatran group compared with the factor Xa-inhibitor group (22.8 [95% confidence interval [CI], 19.7–26.3] and 33.8 [95% CI, 30.5–37.6] events per 10 000 person-years, respectively). In adjusted analyses, dabigatran was associated with a significantly lower incidence rate of SAB compared with factor Xa-inhibitors (incidence rate ratio, .76; 95% CI, .63–.93). Conclusions Treatment with dabigatran was associated with a significantly lower incidence rate of SAB compared with treatment with factor Xa-inhibitors.

Comparison of the Antithrombotic Effectiveness of the Direct Thrombin Inhibitor, Dabigatran Etexilate, and Two Factor Xa Inhibitors in an A-V Shunt Model of Thrombosis in Rabbits.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3154-3154 ◽  
Author(s):  
Joanne van Ryn ◽  
Norbert Hauel ◽  
Henning Priepke ◽  
Kai Gerlach ◽  
Annette Schuler-Metz ◽  
...  
Keyword(s):  
Dabigatran Etexilate ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Direct Thrombin Inhibitor ◽  
Factor Xa Inhibitors ◽  
Thrombin Inhibitor ◽  
Factor Xa Inhibitor ◽  
Antithrombotic Activity ◽  
Antithrombotic Efficacy ◽  
Dose Dependent

Abstract Inhibition of two key serine proteases in the coagulation cascade, thrombin (IIa) and factor Xa, are currently being exploited for direct, oral antithrombotic activity in the clinic. However, it is still unclear if one form of coagulation factor inhibition is more effective than the other. Thus, the objective of this study was to test the antithrombotic efficacy of the clinically advanced compounds, the potent direct thrombin inhibitor, dabigatran etexilate and rivaroxaban, a potent direct factor Xa inhibitor in the rabbit A-V shunt model of thrombosis. In addition, another internally developed factor Xa inhibitor, BI42551, with properties similar to those in clinical development was tested. All three compounds have affinities (Ki) for their respective coagulation factor in the low nM range, i.e. human thrombin with dabigatran or human factor Xa with rivaroxaban or BI42551. In addition, each is at least >700-fold selective for its human coagulation factor, dabigatran etexilate for IIa vs Xa and the factor Xa inhibitors for Xa vs IIa. These compounds are highly selective inhibitors not only of the human enzyme, but also have similar values for rabbit thrombin and Xa, respectively. All experiments were performed according to German animal ethics guidelines. The femoral artery and vein of anesthetised rabbits were connected with polyethylene tubing containing a fixed length of suture, pre-soaked in tissue factor. Blood flow through the shunt was maintained over 40 min, after which the suture with any thrombus was removed from the shunt and weighed. The prodrug dabigatran etexilate and the factor Xa inhibitors were given in doses of 3 and 10 mg/kg orally and the rabbits were anesthetised either 90 min or at the highest dose, also 6.5 hrs after drug administration. There was a dose-dependent reduction of thrombus formation with all three compounds as compared to control. Antithrombotic efficacy at 3 and 10 mg/kg is shown as % inhibition of control measured 2 hrs after drug administration (table, columns 2&3). These effects were long-lasting, as significant antithrombotic activity was also measured 7 hrs post administration (last column). Plasma levels of all compounds were dose-dependent and clotting tests correlated well with dose. 3 mg/kg–2 hrs 10 mg/kg–2 hrs 10 mg/kg–7 hrs Dabigatran etexilate 61.7 ± 8.7 82.1 ± 5.5 59.5 ± 17.6 Rivaroxaban 43.2 ± 7.7 64.5 ± 8.1 41.0 ± 8.4 BI42551 31.1 ± 10.7 70.3 ± 3.3 39.9 ± 14.7 These results show that both thrombin and factor Xa inhibition are effective methods of inhibiting thrombosis in a rabbit AV shunt model. All drugs had potent and long-lasting effects after a single oral administration in this model, though dabigatran showed a trend to elevated antithrombotic efficacy at both 2 and 7 hrs. However, in the clinical setting differences in antithrombotic treatment may also be related to differences in pharmacokinetic profiles, drug interactions or metabolism, or the individual side effect profiles of each compound.

Abstract 20326: Impact of Gender on Clinical Outcomes in Non-Valvular Atrial Fibrillation: Contemporary Perspective From the GARFIELD Registry

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
John Camm ◽  
Samuel Z Goldhaber ◽  
Giuseppe Ambrosio ◽  
Petr Jansky ◽  
Wael Al Mahmeed ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vascular Disease ◽  
Clinical Outcomes ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
History Of ◽  
Ischaemic Attack ◽  
Contemporary Perspective ◽  
Baseline Characteristics

Purpose: To evaluate the influence of gender on baseline characteristics and 1-year clinical outcomes in patients with non-valvular atrial fibrillation (AF). Methods: In the ongoing, international registry GARFIELD, a total of 12,458 prospective patients were enrolled at 739 randomly selected sites in 30 countries between March 2010 and January 2013. Results: Compared with men, women with AF were more likely to be older and have a history of hypertension or venous thromboembolism, but less likely to have a history of vascular disease. Use of antithrombotic therapy was similar in the two groups. At 1-year follow-up, the hazard ratio for women versus men, adjusted for age group, use of vitamin K antagonist, Factor Xa inhibitor, direct thrombin inhibitor, and antiplatelet, congestive cardiac failure, hypertension, diabetes, stroke/transient ischaemic attack, and vascular disease, was 0.815 (95% confidence interval, 0.695-0.957) for the incidence of all-cause mortality, 1.414 (1.053-1.899) for the incidence of stroke/systemic embolism (SE), and 1.024 (0.714-1.470) for the incidence of major bleeding. Conclusion: These findings suggest that women with non-valvular AF have a lower mortality rate despite a higher stroke/SE rate compared with men.

scholarly journals Clinical outcomes of Japanese atrial fibrillation patients with combined valvular heart disease: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Doi ◽  
K Ishigami ◽  
Y Aono ◽  
S Ikeda ◽  
Y Hamatani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Incidence Rate ◽  
Clinical Outcomes ◽  
Valvular Heart Disease ◽  
Cardiac Death ◽  
Clinical Characteristics ◽  
Valve Disease ◽  
The Impact

Abstract Background We previously reported that valvular heart disease (VHD) was not at the significant risk of stroke/systemic embolism (SE), but was associated with an increased risk of hospitalization for heart failure (HF) in Japanese atrial fibrillation patients. However, the impact of combined VHD on clinical outcomes has been little known. Purpose The aim of this study is to investigate the prevalence of combined VHD and its clinical characteristics and impact on outcomes such as stroke/SE, all-cause death, cardiac death and hospitalization for HF. Method The Fushimi AF Registry is a community-based prospective survey of AF patients in one of the wards of our city which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. In the entire cohort, echocardiography data were available for 3,574 patients. 68 AF patients with prosthetic heart valves were excluded and we compared clinical characteristics and outcomes between 488 single VHD (103 Aortic valve disease (AVD), 315 mitral valve disease (MVD), 70 tricuspid valve disease (TVD)) and 158 combined VHD (46 AVD and MVD, 11 AVD and TVD, 66 MVD and TVD, 35 AVD and MVD and TVD). Result Compared with single VHD, patients with combined VHD were older (combined vs. single VHD: 78.5 vs. 76.0 years, respectively; p<0.01), more likely to have persistent/permanent type AF (73.4% vs. 63.9%, p=0.02) and prescription of warfarin (63.1% vs. 53.8%, p=0.04). Combined VHD was less likely to have diabetes mellitus (13.9% vs. 23.6%, p=0.01) and dyslipidemia (26.6% vs. 40.4%, p<0.01). Sex, body weight, hypertension, pre-existing HF were comparable between the two groups. During the median follow-up of 1,474 days, the incidence rate of stroke/SE was not significantly different between the two groups (1.58 vs. 1.89 per 100 person-years, respectively, log rank p=0.10). The incidence rate of all-cause death (7.35 vs. 5.33, p=0.65), cardiac death (1.20 vs. 0.99, p=0.91) and hospitalization for HF (5.55 vs. 4.43, p=0.53) were also not significantly different. We previously reported AVD had significant impacts on cardiac adverse outcomes in AF patients, and we further analyzed event rates between combined VHD including AVD (AVD and MVD/TVD) and without AVD (MVD and TVD). Combined VHD with AVD group had higher incidence rate of all-cause death (10.7 vs. 5.79, p=0.03) than that without AVD group. However, the incidence rate of stroke/SE (1.98 vs. 1.56, p=0.59), cardiac death (0.98 vs. 1.14, p=0.68), hospitalization for HF (8.03 vs. 5.38, p=0.17) were not significantly different between the two groups. Conclusion As compared with single VHD, the risk of stroke/SE, all-cause death, cardiac death and hospitalization for HF in combined VHD was not significantly different. Among patients with combined VHD, those having AVD had higher incidence rate of all-cause death than those without AVD. Figure 1 Funding Acknowledgement Type of funding source: None

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