Stefan H Hohnloser

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (372)

  • [Show abstract] [Hide abstract] ABSTRACT: Importance: In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban. Objective: To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria. Design, setting, and participants: Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016. Main outcomes and measures: Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat. Results: Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance. Conclusions and relevance: Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion. Trial registration: Identifier: NCT00412984.
    Article · Jul 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Aims Pocket haematoma is a common complication after defibrillator [implantable cardioverter defibrillator (ICD)] implantation, which is not only painful, but also increases the risk of device-related infection, and possibly embolic events. The present study seeks to evaluate the rate and predictors of clinically significant pocket haematoma. Methods and results This study included 2500 patients receiving an ICD in the SIMPLE trial. A clinically significant pocket haematoma was defined as a haematoma that required re-operation or interruption of oral anticoagulation (OAC) therapy. Clinically significant pocket haematoma occurred in 56 of 2500 patients (2.2%) of which 6 (10.7%) developed device-related infection. Patients who developed pocket haematoma were older (mean age 67.6 ± 8.8 years vs. 62.7 ± 11.6 years, P < 0.001), were more likely to have permanent atrial fibrillation (30.4 vs. 6.7%, P < 0.001) and a history of stroke (17.9 vs. 6.7%, P = 0.004), or were more likely to receive peri-operative OAC (50.0 vs. 28.4%, P < 0.001), unfractionated heparin (16.1 vs. 5.2%, P = 0.003), or low-molecular-weight heparin (37.5 vs. 17.5%, P < 0.001). Independent predictors of wound haematoma on multivariable analysis included the use of heparin bridging (OR 2.65, 95% CI 1.48–4.73, P = 0.001), sub-pectoral location of ICD (OR 2.00, 95% CI 1.12–3.57, P =0.020), previous stroke (OR 2.47, 95% CI 1.20–5.10, P = 0.015), an upgrade from permanent pacemaker (OR 2.52, 95% CI 1.07–5.94, P = 0.035), and older age (OR 1.03, 95% CI 1.00–1.06, P = 0.049). Conclusion Pocket haematoma remains an important complication of ICD implantation and is associated with a high risk of infection. Independent predictors of pocket haematoma include heparin bridging, prior stroke, sub-pectoral placement of ICD, older age, and upgrade from a pacemaker.
    Article · Jun 2016 · Europace
  • Ziad Hijazi · Stefan H. Hohnloser · Ulrika Andersson · [...] · Lars Wallentin
    [Show abstract] [Hide abstract] ABSTRACT: Importance Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time. Objectives To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment. Design, Setting, and Participants The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate. Main Outcomes and Measures Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations. Results Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with worsening renal function. Conclusions and Relevance In patients with atrial fibrillation, declining renal function was more common in elderly patients and those with cardiovascular comorbidities. Worsening renal function was associated with a higher risk of subsequent cardiovascular events and bleeding. The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function. Trial Registration Identifier: NCT00412984.
    Article · Jun 2016 · JAMA Cardiology
  • Julia W. Erath · Mate Vamos · Stefan H. Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: Background The effects of digitalis on mortality in patients with structural heart disease are controversially discussed. We aimed to assess the effects of digitalis administration in ICD recipients. Methods This retrospective analysis comprises 1020 consecutive patients who received an ICD at our institution and who were followed for up to 10 years (median 37 months). Results A total of 438 patients were receiving digitalis at the time of ICD implantation and 582 did not. Patients on digitalis were more often in atrial fibrillation, had more often a prolonged QRS-duration≥120 ms, a severely impaired LVEF and higher NYHA classification heart failure. Crude Kaplan-Meier analysis demonstrated significantly higher mortality in patients on digitalis (HR=2.47, 95% C. I. 1.87-3.25; p=0.001). After adjustment for patient characteristics found statistically significant in adjusted Cox-regression analysis (age, gender, NYHA-classification and QRS-duration≥120ms), a HR of 1.65 remained (95% C. I. 1.14-2.39; p=0.01). Patients on digitalis died more often from cardiac arrhythmic and cardiac non arrhythmic causes than patients not on digitalis (p=0.04). There was no difference in mortality between patients receiving digitoxin and those receiving digoxin (HR=1.55; 95% C. I. 0.74-3.25; p=0.25). Conclusion In this large ICD patient population, digitalis use at baseline was independently associated with increased mortality even after careful adjustment for possible confounders. Digitalis should be used with great caution in this population.
    Article · Apr 2016
  • Mate Vamos · Stefan H. Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: This article provides a contemporary review of the current role of amiodarone and dronedarone in patients with atrial fibrillation who need to undergo rhythm control therapy for relief of symptoms. Amiodarone is the most widely prescribed antiarrhythmic drug for this indication. Recent findings show that its use is not associated with increased mortality even in patients with advanced structural heart disease. However, its extracardiac side effect profile may limit its widespread use. Dronedarone appears to be a useful drug in patients with paroxysmal or persistent atrial fibrillation. However, the compound cannot be used in patients with heart failure. In permanent atrial fibrillation, dronedarone is likewise contraindicated based on findings from the PALLAS trial.
    Article · Apr 2016 · Trends in cardiovascular medicine
  • Mate Vamos · Jorg Honold · Gabor Z. Duray · Stefan H. Hohnloser
    Article · Apr 2016 · JACC Clinical Electrophysiology
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    Full-text Article · Mar 2016 · Journal of the American Heart Association
  • [Show abstract] [Hide abstract] ABSTRACT: Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation.
    Article · Feb 2016 · European Heart Journal
  • [Show abstract] [Hide abstract] ABSTRACT: The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes.
    Article · Feb 2016 · European Heart Journal
  • Mate Vamos · Riccardo Cappato · Francis E. Marchlinski · [...] · Stefan H. Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: Rivaroxaban is increasingly used in patients undergoing catheter ablation of atrial fibrillation (AF). In the absence of large controlled trials, a comprehensive meta-analysis of the literature appears to be the best way to obtain reliable evidence on rare peri-procedural outcomes such as thromboembolic or bleeding events. We aimed to provide a detailed analysis of currently available data on safety and efficacy of peri-procedural rivaroxaban in patients undergoing AF ablation. We performed a systematic search of the English language literature for studies comparing peri-procedural rivaroxaban therapy with vitamin K antagonists (VKAs) and reporting detailed data on bleeding and/or thromboembolic complications. The Peto odds ratio (POR) was used to pool data into a fixed-effect meta-analysis. A total of 7400 patients undergoing catheter ablation were included in 15 observational and 1 randomized studies of which 1994 were receiving rivaroxaban and 5406 VKA. The risk of thromboembolism trended to be lower in the rivaroxaban group [4/1954 vs. 19/5219, POR 0.40, 95% confidence interval (CI), 0.16–1.01, P = 0.052]. Major bleeding events occurred in 23 of 1994 cases (1.15%) in the rivaroxaban and 90 of 5406 (1.66%) in the VKA group (POR 0.74, 95% CI, 0.46–1.21, P = 0.23). A total of 87 minor bleeding events were reported in 1753 patients (4.96%) in the rivaroxaban group and in 165 of 4009 patients (4.12%) in the VKA group (POR 0.84, 95% CI 0.63-1.11, p = 0.22). In patients undergoing AF ablation, rivaroxaban appears to be an effective and safe alternative to VKA.
    Article · Jan 2016 · Europace
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    Full-text Article · Dec 2015 · Journal of the American College of Cardiology
  • S.H. Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: Non-vitamin K oral anticoagulants (NOAC) have now become established for stroke prevention in atrial fibrillation. The efficacy is at least as good if not better than that of vitamin K antagonists (VKA). The risk for major bleeding is less for NOAC than for VKA, with a particular superiority concerning the avoidance of intracerebral hemorrhage. The outcome after major bleeding is more favorable in patients receiving NOAC compared to those treated with VKA. Specific reversal agents for NOAC are currently being tested which neutralize the effects of NOAC within minutes and the clinical introduction of the first one for the thrombin inhibitor dabigatran is imminent. Such specific antidotes will further improve the safety profile of NAOC.
    Article · Dec 2015 · Herz
  • Mate Vamos · Jeff S Healey · Jia Wang · [...] · Stefan H Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: Background: SIMPLE randomized 2,500 patients receiving a first ICD/CRT-D device to defibrillation testing (DT) or not. It demonstrated that DT did not improve shock efficacy or reduce mortality. Objective: This prospective sub-study evaluated the effect of DT on postoperative troponin concentrations and their predictive value for total and arrhythmic mortality. Methods: Troponin was measured between 6 and 24 hours following ICD implantation in 2200/2500 patients. Results: A postoperative serum troponin level above the upper limit of normal (ULN) was more common in patients undergoing DT (N=509, 46.4%) than in those not having DT (N=456, 41.3%; p=0.02). After excluding patients with known preoperative troponin > ULN, consistent findings were observed (42.1% vs. 37.5%, p=0.04). During a mean follow-up of 3.1 ± 1.0 years, the annual mortality rate was increased in patients with a postoperative troponin > ULN (adjusted HR 1.43, 95% CI, 1.15-1.76, p=0.001) irrespective of DT or not. Likewise, patients with elevated troponin levels had a significantly higher risk of arrhythmic death (adjusted HR 1.80, 95% CI, 1.23-2.63, p=0.002). The rate of first appropriate ICD shock (adjusted HR 0.89, 95% CI, 0.71-1.12, p=0.32) or failed appropriate shock (adjusted HR 1.02, 95% CI, 0.59-1.76, p= 0.95) were similar in patients with or without troponin elevation. Conclusion: DT at time of ICD implantation is associated with increased troponin levels indicating subclinical myocardial injury caused by the procedure. Elevated troponin levels but not defibrillation testing, seem to predict clinical outcomes in ICD recipients.
    Article · Nov 2015 · Heart rhythm: the official journal of the Heart Rhythm Society
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    Stefan H. Hohnloser · Riccardo Cappato · Michael D. Ezekowitz · [...] · Martin van Eickels
    [Show abstract] [Hide abstract] ABSTRACT: Aims We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. Methods and results The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of A 421 pound and (sic)360 per patient in UK and Italian settings, respectively. Conclusion The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA.
    Full-text Article · Oct 2015 · Europace
  • Julia Erath · Máté Vámos · Stefan H. Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: Bei Patienten mit Vorhofflimmern wird die Mortalität und Morbidität in erster Linie durch thromboembolische Komplikationen erhöht. Das Risiko für ischämische Schlaganfälle ist bei Vorhofflimmern 4- bis 5-fach höher als bei sinusrhythmischen Patienten. Für die Schlaganfallprävention wird Aspirin nicht mehr empfohlen und die Antikoagulation mit Vitamin-K-Antagonisten weist in der Therapie zahlreiche Limitierungen auf. Die direkten oralen Antikoagulanzien sind sehr viel einfacher anzuwenden und haben weitere Vorteile wie eine kurze Halbwertszeit oder fehlende bzw. einzelne Wechselwirkungen mit Nahrungsmitteln bzw. anderen Medikamenten. Vor allem ist ein regelmäßiges Monitoring der blutverdünnenden Wirkung nicht nötig.
    Article · Sep 2015
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. Methods and results: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Conclusion: Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.
    Full-text Article · Aug 2015 · European Heart Journal
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    [Show abstract] [Hide abstract] ABSTRACT: Vitamin K-dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR). This study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial. Of the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated. GFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (-3.68 ± 0.24 ml/min) compared with DE 110 mg (-2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (-2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range <65%) exhibited a faster decline in GFR. A more pronounced decline in GFR was associated with previous warfarin use and with the presence of diabetes. Patients with atrial fibrillation receiving oral anticoagulation exhibited a decline in renal function that was greater in those taking warfarin versus DE, and it was amplified by diabetes and previous vitamin K antagonist use. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Full-text Article · Jun 2015 · Journal of the American College of Cardiology
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    Riccardo Cappato · Francis E Marchlinski · Stefan H Hohnloser · [...] · Andrea Natale
    [Show abstract] [Hide abstract] ABSTRACT: VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA). Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar. In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy. trial registration number is NCT01729871. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
    Full-text Article · May 2015 · European Heart Journal
  • Mate Vamos · Julia W Erath · Stefan H Hohnloser
    [Show abstract] [Hide abstract] ABSTRACT: There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the subgroup of publications comprising 235 047 AF patients. Among 91.379 heart failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14, 95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email:
    Article · May 2015 · European Heart Journal
  • Stefan H Hohnloser · Máté Vámos · Hans-Christoph Diener
    [Show abstract] [Hide abstract] ABSTRACT: The development of the direct oral anticoagulants (DOACs) represents one of the major breakthroughs in modern medicine over the last decade. Compared to vitamin K antagonists, all DOACs (dabigatran as a thrombin-Inhibitor, rivaroxaban, apixaban and edoxaban as factor Xa inhibitors) are much easier to handle due to their pharmacological properties. All DOACS are more efficacious and safer as vitamin K antagonists as demonstrated in the pivotal studies in more than 71 000 patients. Particularly the much lower risk of intracerebral bleeding complications is the reason why the DOACs should be preferred over vitamin K antagonists in patients with non-valvular atrial fibrillation. © Georg Thieme Verlag KG Stuttgart · New York.
    Article · May 2015 · DMW - Deutsche Medizinische Wochenschrift

Publication Stats

23k Citations


  • 2007
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2006
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
    • The University of Calgary
      Calgary, Alberta, Canada
    • University of Toronto
      Toronto, Ontario, Canada
  • 2003
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany