Impact of dronedarone in atrial fibrillation and flutter on stroke reduction

Christine Benn Christiansen1, Christian Torp-Pedersen1, Lars Køber21Department of Cardiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; 2Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Dronedarone has been developed for treatment of atrial fibrillation (AF) or atrial flutter (AFL). It is an amiodarone analogue but noniodinized and without the same adverse effects as amiodarone.Objective and methods: This is a review of 7 studies (DAFNE, ADONIS, EURIDIS, ATHENA, ANDROMEDA, ERATO and DIONYSOS) on dronedarone focusing on efficacy, safety and prevention of stroke. There was a dose-finding study (DAFNE), 3 studies focusing on maintenance of sinus rhythm (ADONIS, EURIDIS and DIONYSOS), 1 study focusing on rate control (ERATO) and 2 studies investigating mortality and morbidity (ANDROMEDA and ATHENA).Results: The target dose for dronedarone was established in the DAFNE study to be 400 mg twice daily. Both EURIDIS and ADONIS studies demonstrated that dronedarone was superior to placebo for maintaining sinus rhythm. However, DIONYSOS found that dronedarone is less efficient at maintaining sinus rhythm than amiodarone. ERATO concluded that dronedarone reduces ventricular rate in patients with chronic AF. The ANDROMEDA study in patients with severe heart failure was discontinued because of increased mortality in dronedarone group. Dronedarone reduced cardiovascular hospitalizations and mortality in patients with AF or AFL in the ATHENA trial. Secondly, according to a post hoc analysis a significant reduction in stroke was observed (annual rate 1.2% on dronedarone vs 1.8% on placebo, respectively [hazard ratio 0.66, confidence interval 0.46 to 0.96, P = 0.027]). In total, 54 cases of stroke occurred in 3439 patients (crude rate 1.6%) receiving dronedarone compared to 76 strokes in 3048 patients on placebo (crude rate 2.5%), respectively.Conclusion: Dronedarone can be used for maintenance of sinus rhythm and can reduce stroke in patients with AF who receive usual care, which includes antithrombotic therapy and heart rate control.Keywords: atrial fibrillation, stroke, dronedaron

Oral tranexamic acid and thrombosis risk in women

BACKGROUND: Oral tranexamic acid is effective for heavy menstrual bleeding, but the thrombosis risk with this treatment is largely not studied. METHODS: Using nationwide registries, we assessed associations between use of oral tranexamic acid and risk of deep-vein thrombosis or pulmonary embolism and arterial thrombosis in heart or brain in a nationwide historical prospective cohort of Danish women aged 15 to 49 years in the period 1996–2017. Exclusion criteria included potential confounding factors such as history of thromboembolism, anticoagulation therapy, thrombophilia, and cancer. FINDINGS: Among 2·0 million women followed for 13·8 million person-years, 3,392 venous thromboembolisms and 4,198 arterial thromboses occurred. A total of 63,896 women (3·2%) filled 146,729 prescriptions of oral tranexamic acid during follow-up with median filled prescription per user being one of 15 g. The age-standardised incidence rate of venous thromboembolism was 11·8 (95% CI 4·6 to 30·2) per 10,000 person-years in oral tranexamic acid use compared to 2·5 (2·4 to 2·6) per 10,000 person-years in non-use. For arterial thrombosis, the age-standardised incidence rate per 10,000 person-years was 3·4 (1·1 to 10·7) among exposed compared to 3·0 (2·9 to 3·1) in non-exposed. Comparing oral tranexamic acid use with non-use, the adjusted incidence rate ratio was 4·0 (1·8 to 8·8) for venous thromboembolism and 1·3 (0·4 to 4·2) for arterial thrombosis. Number needed to harm per five days of treatment was 78,549 women for venous thromboembolism. INTERPRETATION: We found use of oral tranexamic acid to be positively associated with venous thromboembolism. However, number needed to harm per five days of treatment was high

Risk of stroke, myocardial infarction, and death among patients with retinal artery occlusion and the effect of antithrombotic treatment

PURPOSE: To evaluate the risk of future stroke, myocardial infarction (MI), and death of patients with retinal artery occlusion (RAO) and the effect of various antithrombotic treatments as secondary prevention. METHODS: This cohort study was based on nationwide health registries and included the entire Danish population from 2000 to 2018. All patients with RAO were identified and their adjusted risks of stroke, MI, or death in time periods since RAO were compared with those of the Danish population. Furthermore, antithrombotic treatment of patients with RAO was determined by prescription claims, and the association with the risk of stroke, MI, or death was assessed using multivariate Poisson regression models and expressed as rate ratios (RR) with 95% confidence intervals (95% CIs). RESULTS: After inclusion, 6628 individuals experienced a first-time RAO, of whom 391 had a stroke, 66 had a MI, and 402 died within the first year after RAO. RAO was associated with an increased risk of stroke, MI, or death which persisted for more than 1 year for all three outcomes but was highest on days 3 to 14 after RAO for stroke, with an adjusted RR of 50.71 (95% CI, 41.55–61.87), and on days 14 to 90 after RAO for MI and death, with adjusted RRs of 1.98 (95% CI, 1.25–3.15) and 1.64 (95% CI, 1.28–189), respectively. Overall, antithrombotic treatment was not associated with any protective effect the first year. CONCLUSIONS: Patients with RAO had an increased risk of stroke, MI, or death. No protective effect of antithrombotic treatment was shown. TRANSLATIONAL RELEVANCE: These findings are relevant to the management of patients with RAO

Carvedilol in the treatment of chronic heart failure: Lessons from The Carvedilol Or Metoprolol European Trial

Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both metoprolol and carvedilol have demonstrated beneficial effects in placebo-controlled trials. In The Carvedilol Or Metoprolol European Trial (COMET) two beta blockers were compared in a double-blind randomized matter. This is the first direct comparison between metoprolol and carvedilol of long-term effect on survival in patients with chronic heart failure. The all-cause mortality was signif icantly reduced in the favour of carvedilol. The dose and formulation of metoprolol used in this trial has caused debate, and it has been questioned whether a similar beta1-blockade is obtained in the two intervention groups. At this time there is an unresolved debate as to whether carvedilol is a superior beta-blocker or whether differences in beta1-blockade explained the results of COMET

Consequences of overutilization and underutilization of thrombolytic therapy in clinical practice

AbstractOBJECTIVESThe aim of this study was to evaluate the consequences, measured as mortality and in-hospital stroke, of the use of thrombolytic therapy among patients with acute myocardial infarction (AMI), who do not fulfill accepted criteria or who have contraindications to thrombolytic therapy (i.e., overutilization) and among patients who are withheld thrombolytic treatment despite fulfilling indications and having no contraindications (i.e., underutilization).BACKGROUNDThe implementation of treatment with thrombolysis in clinical practice is not in accordance with the accepted criteria from randomized studies. The consequence has been over- and underutilization of thrombolytic therapy among patients with AMI in clinical practice. The outcome of overutilization of thrombolytic therapy has not been described previously.METHODSWe examined 6,676 consecutive patients admitted to the hospital with an AMI and recorded characteristics, in-hospital complications and long-term mortality.RESULTSOverall, 41% of the patients received thrombolytic therapy. Thrombolytic therapy was underutilized in 14.3% and overutilized in 12.9% of the patients. The use of thrombolytic therapy was associated with reduced mortality in every subgroup examined, including patients without an accepted indication, with an accepted indication and in patients with prior stroke. The risk ratio of in-hospital stroke was not increased in connection with thrombolytic therapy, not even in patients with prior stroke (relative risk = 0.237, 95% confidence interval: 0.031 to 1.810, p = 0.17).CONCLUSIONSWith the large benefit known to be associated with thrombolytic therapy and the favorable result of thrombolytic therapy in patients with contraindications observed in this study, we conclude that a formal evaluation of thrombolytic therapy in wider patient categories is warranted

Diabetes is an independent predictor of survival 17 years after myocardial infarction: follow-up of the TRACE registry

<p>Abstract</p> <p>Background</p> <p>In patients hospitalized for myocardial infarction, there are limited data examining the long-term prognostic effect of diabetes.</p> <p>The aim of this study was to systematically evaluate the development of diabetes as an independent long-term prognostic factor after myocardial infarction.</p> <p>Methods</p> <p>Prospective follow-up of 6676 consecutive MI patients screened for entry in the Trandolapril Cardiac Evaluation (TRACE) study. The patients were analysed by Kaplan-Meier survival analysis, landmark analysis and Cox proportional hazard models and outcome measure was all-cause mortality.</p> <p>Results</p> <p>The mortality in patients with diabetes was 82,7% at 10 years of follow-up and 91,1% at 15 years of follow-up, while patients without diabetes had a mortality of 60,2% at 10 years of follow-up and 72,9% at 15 years of follow-up (p < 0.0001). Landmark analysis continued to show prognostic significance of diabetes throughout the duration of follow-up. Multivariable Cox proportional-hazards model showed that the hazard ratio for death in patients with diabetes overall was 1.47 (95% confidence intervals (CI) 1.35-1.61) and varied between 1.19 (CI 1.04-1.37) and 2.13 (CI 1.33-3.42) in the 2-year periods of follow-up.</p> <p>Conclusions</p> <p>Diabetes is an important independent long-term prognostic factor after MI and continues to predict mortality even 17 years after index MI.</p> <p>This underscores the importance of aggressive diagnostic and therapeutic approach in diabetes patients with MI.</p