| 1. |
- Spronk, H. M. H., et al.
(författare)
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Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
- 2018
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Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
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Forskningsöversikt (refereegranskat)abstract
- Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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| 2. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 3. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Tidskriftsartikel (refereegranskat)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 4. |
- De Ferrari, G. M., et al.
(författare)
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Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure
- 2011
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 32:7, s. 847-855
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. METHODS AND RESULTS: This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 +/- 11 years, LV ejection fraction (LVEF) 23 +/- 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 +/- 76 to 471 +/- 111 m), LVEF (from 22 +/- 7 to 29 +/- 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. CONCLUSIONS: This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
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| 5. |
- Nieuwlaat, R, et al.
(författare)
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Atrial fibrillation management: a prospective survey in ESC Member Countries - The Euro Heart Survey on Atrial Fibrillation
- 2005
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 26:22, s. 2422-2434
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Tidskriftsartikel (refereegranskat)abstract
- Aims To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Methods and results Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. Conclusion This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy.
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| 6. |
- Schnabel, Renate B., et al.
(författare)
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Searching for Atrial Fibrillation Poststroke : A White Paper of the AF-SCREEN International Collaboration
- 2019
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Ingår i: Circulation. - 1524-4539. ; 140:22, s. 1834-1850
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.
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| 7. |
- van Deursen, Caroline J M, et al.
(författare)
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Vectorcardiography for Optimization of Stimulation Intervals in Cardiac Resynchronization Therapy.
- 2015
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Ingår i: Journal of cardiovascular translational research. - : Springer Science and Business Media LLC. - 1937-5395 .- 1937-5387. ; 8:2, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- Current optimization of atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) is time consuming and subject to noise. We aimed to prove the principle that the best hemodynamic effect of CRT is achieved by cancelation of opposing electrical forces, detectable from the QRS morphology in the 3D vectorcardiogram (VCG). Different degrees of left (LV) and right ventricular (RV) pre-excitation were induced, using variation in AV intervals during LV pacing in 20 patients with left bundle branch block (LBBB) and variation in VV intervals during biventricular pacing in 18 patients with complete AV block or atrial fibrillation. The smallest QRS vector area identified stimulation intervals with minimal systolic stretch (median difference [IQR] 20ms [-20, 20ms] and maximal hemodynamic response (10ms [-20, 40ms]). Reliability of VCG measurements was superior to hemodynamic measurements. This study proves the principle that VCG analysis may allow easy and reliable optimization of stimulation intervals in CRT patients.
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| 8. |
- Hendriks, Jeroen, et al.
(författare)
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Integrated specialized atrial fibrillation clinics reduce all-cause mortality: post hoc analysis of a randomized clinical trial
- 2019
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Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 21:12, s. 1785-1792
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Tidskriftsartikel (refereegranskat)abstract
- Aims An integrated chronic care programme in terms of a specialized outpatient clinic for patients with atrial fibrillation (AF), has demonstrated improved clinical outcomes. The aim of this study is to assess all-cause mortality in patients in whom AF management was delivered through a specialized outpatient clinic offering an integrated chronic care programme. Methods and results Post hoc analysis of a Prospective Randomized Open Blinded Endpoint Clinical trial to assess all-cause mortality in AF patients. The study included 712 patients with newly diagnosed AF, who were referred for AF management to the outpatient service of a University hospital. In the specialized outpatient clinic (AF-Clinic), comprehensive, multidisciplinary, and patient-centred AF care was provided, i.e. nurse-driven, physician supervised AF treatment guided by software based on the latest guidelines. The control group received usual care by a cardiologist in the regular outpatient setting. After a mean follow-up of 22months, all-cause mortality amounted 3.7% (13 patients) in the AF-Clinic arm and 8.1% (29 patients) in usual care [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.23-0.85; P = 0.014]. This included cardiovascular mortality in 4 AF-Clinic patients (1.1%) and 14 patients (3.9%) in usual care (HR 0.28; 95% CI 0.09-0.85; P = 0.025). Further, 9 patients (2.5%) died in the AF-Clinic arm due to a non-cardiovascular reason and 15 patients (4.2%) in the usual care arm (HR 0.59; 95% CI 0.26-1.34; P = 0.206). Conclusion An integrated specialized AF-Clinic reduces all-cause mortality compared with usual care. These findings provide compelling evidence that an integrated approach should be widely implemented in AF management.
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| 9. |
- Kowey, Peter R, et al.
(författare)
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Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death : the ALPHEE study
- 2011
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 124:24, s. 2649-2660
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. METHODS AND RESULTS: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS: Celivarone was not effective for the prevention of ICD interventions or sudden death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00993382.
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| 10. |
- Nieuwlaat, Robby, et al.
(författare)
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Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation
- 2006
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 27:24, s. 3018-3026
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Tidskriftsartikel (refereegranskat)abstract
- Aims To describe guideline adherence and application of different stroke risk strati. cation schemes regarding antithrombotic therapy in real-life atrial. brillation (AF) patients and to assess which factors influence antithrombotic management decisions. Methods and results The Euro Heart Survey enrolled 5333 AF patients in 35 countries, in 2003 and 2004. Prescription of antithrombotic drugs, especially oral anticoagulation (OAC), was hardly tailored to the patient's stroke risk pro. le as indicated by the joint guidelines of the American College of Cardiology, American Heart Association, and the European Society of Cardiology, ACCP guidelines, or CHADS(2) and Framingham risk scores. In multivariable analysis, only a limited number of the well-known stroke risk factors triggered OAC prescription. In contrast, less relevant factors, of which clinical type of AF and availability of an OAC monitoring outpatient clinic were the most marked, played a significant role in OAC prescription. Electrical cardioversions and catheter ablations clearly triggered OAC prescription, whereas pharmacological cardioversions even in the presence of stroke risk factors did not. Conclusion Antithrombotic therapy in AF is hardly tailored to the patient's stroke risk pro. le. Factors other than well-known stroke risk factors were significantly involved in antithrombotic management decisions. To facilitate this tailored treatment, guideline writers and physician educators should focus on providing one uniform and easy to use stroke risk strati. cation scheme.
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| 11. |
- Nieuwlaat, Robby, et al.
(författare)
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Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation
- 2007
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Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 153:6, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- Background The Euro Heart Survey showed that antithrombotic treatment in patients with atrial fibrillation (AF) was moderately tailored to the 2001 American College of Cardiology, American Heart Association, and European Society of Cardiology (ACC/AHA/ESC) guidelines for the management of AF. What consequences does guideline-deviant antithrombotic treatment have in daily practice? Methods In the Euro Heart Survey on AF (2003-2004), an observational study on AF care in European cardiology practices, information was available on baseline stroke risk profile and antithrombotic drug treatment and on cardiovascular events during 1-year follow-up. Antithrombotic guideline adherence is assessed according to the 2001 ACC/AHA/ESC guidelines. Multivariable logistic regression was performed to assess the association of guideline deviance with adverse outcome. Results The effect of antithrombotic guideline deviance was analyzed exclusively in 3634 high-risk patients with AF because these composed the majority (89%) and because few cardiovascular events occurred in low-risk patients. Among high-risk patients, antithrombotic treatment was in agreement with the guidelines in 61% of patients, whereas 28% were undertreated and 11% overtreated. Compared to guideline adherence, undertreatment was associated with a higher chance of thromboembolism (odds ratio [OR], 1.97; 95% CI, 1.29-3.01; P = .004) and the combined end point of cardiovascular death, thromboembolism, or major bleeding (OR, 1.54; 95% CI, 1.14-2.10; P = .024). This increased risk was nonsignificant for the end point of stroke alone (OR, 1.42; 95% CI, 0.82-2.46; P = .170). Overtreatment was nonsignificantly associated with a higher risk for major bleeding (OR, 1.52; 95% CI, 0.76-3.02; P = .405). Conclusions Antithrombotic undertreatment of high-risk patients with AF was associated with a worse cardiovascular prognosis during 1 year, whereas overtreatment was not associated with a higher chance for major bleeding.
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| 12. |
- Fabritz, Larissa, et al.
(författare)
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Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
- 2021
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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| 13. |
- Hohnloser, Stefan H., et al.
(författare)
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Effect of dronedarone on cardiovascular events in atrial fibrillation
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 360:7, s. 668-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation. METHODS: We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death. Patients were randomly assigned to receive dronedarone, 400 mg twice a day, or placebo. The primary outcome was the first hospitalization due to cardiovascular events or death. Secondary outcomes were death from any cause, death from cardiovascular causes, and hospitalization due to cardiovascular events. RESULTS: The mean follow-up period was 21+/-5 months, with the study drug discontinued prematurely in 696 of the 2301 patients (30.2%) receiving dronedarone and in 716 of the 2327 patients (30.8%) receiving placebo, mostly because of adverse events. The primary outcome occurred in 734 patients (31.9%) in the dronedarone group and in 917 patients (39.4%) in the placebo group, with a hazard ratio for dronedarone of 0.76 (95% confidence interval [CI], 0.69 to 0.84; P<0.001). There were 116 deaths (5.0%) in the dronedarone group and 139 (6.0%) in the placebo group (hazard ratio, 0.84; 95% CI, 0.66 to 1.08; P=0.18). There were 63 deaths from cardiovascular causes (2.7%) in the dronedarone group and 90 (3.9%) in the placebo group (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P=0.03), largely due to a reduction in the rate of death from arrhythmia with dronedarone. The dronedarone group had higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash, and an increased serum creatinine level than the placebo group. Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups. CONCLUSIONS: Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation. (ClinicalTrials.gov number, NCT00174785.)
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| 14. |
- Nieuwlaat, Robby, et al.
(författare)
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Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 29:7, s. 915-922
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Tidskriftsartikel (refereegranskat)abstract
- Aims To assess the relation between the atrial fibrillation (AF) subtype and thrombo-embolic events. Methods and results The observational Euro Heart Survey on AF (2003-04) enrolled 1509 paroxysmal, 1109 persistent, and 1515 permanent AF patients, according to the 2001 American College of Cardiology, American Heart Association, and the European Society of Cardiology guidelines definitions. A 1 year follow-up was performed. Permanent AF patients had at baseline a worse stroke risk profile than paroxysmal and persistent AF patients. In paroxysmal AF, the risk for stroke, any thrombo-embolism, major bleeding and the combined endpoint of cardiovascular mortality, any thrombo-embolism, and major bleeding was comparable with persistent and permanent AF, in both univariable and multivariable analyses. Compared with AF patients without stroke, patients suffering from a stroke had a comparable frequency and duration of AF attacks, but tended to have a worse stroke risk profile at baseline. During 1 year following cardioversion, paroxysmal AF patients had a higher risk for stroke (P = 0.029) and any thrombo-embolism (P = 0.001) than persistent AF patients. Conclusion In the Euro Heart Survey, paroxysmal AF had a comparable risk for thrombo-embolic events as persistent and permanent AF. This observation strengthens the guideline recommendation not to consider the clinical AF subtype when deciding on anticoagulation.
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| 15. |
- Vaduganathan, Muthiah, et al.
(författare)
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Dronedarone for the treatment of atrial fibrillation with concomitant heart failure with preserved and mildly reduced ejection fraction : a post-hoc analysis of the ATHENA trial
- 2022
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:6, s. 1094-1101
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Limited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF. Methods and results: ATHENA was an international, multicentre trial that randomized 4628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with (i) symptomatic HFpEF and HFmrEF (defined as left ventricular ejection fraction [LVEF] >40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), (ii) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF ≤40%), and (iii) those without HF. We assessed effects of dronedarone versus placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or left ventricular dysfunction, and 3672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73 ± 9 years, 37% were women, and had a mean LVEF of 57 ± 9%. Over a mean follow-up of 21 ± 5 months, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69–0.84) without heterogeneity based on HF status (pinteraction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity (pinteraction = 0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favoured dronedarone versus placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant in this subgroup. Conclusions: Dronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.
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