Effects of apixaban compared with warfarin as gain in event-free time – a novel assessment of the results of the ARISTOTLE trial

Background A novel approach to determine the effect of a treatment is to calculate the delay of event, which estimates the gain of event-free time. The aim of this study was to estimate gains in event-free time for stroke or systemic embolism, death, bleeding events, and the composite of these events, in patients with atrial fibrillation randomized to either warfarin or apixaban in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE). Design The ARISTOTLE study was a randomized double-blind trial comparing apixaban with warfarin. Methods Laplace regression was used to estimate the delay in time to the outcomes between the apixaban and the warfarin group in 6, 12, 18 and 22 months of follow-up. Results The gain in event-free time for apixaban versus warfarin was 181 (95% confidence interval 76 to 287) days for stroke or systemic embolism and 55 (–4 to 114) days for death after 22 months of follow-up. The corresponding gains in event-free times for major and intracranial bleeding were 206 (130 to 281) and 392 (249 to 535) days, respectively. The overall gain for the composite of all these events was a gain of 116 (60 to 171) days. Conclusions In patients with atrial fibrillation, 22 months of treatment with apixaban, as compared with warfarin, provided gains of approximately 6 months in event-free time for stroke or systemic embolism, 7 months for major bleeding and 13 months for intracranial bleeding.

Reflexões sobre o estudo CABANA (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial)

A fibrilação atrial se consolidou nas últimas décadas como um grave problema de saúde pública, considerando o seu notório aumento de prevalência com o envelhecimento aliado ao aumento da sobrevida da população. Dados do Framingham Heart Study indicam que, mesmo em um cenário ótimo de ausência dos clássicos fatores de risco para sua ocorrência, como tabagismo, consumo abusivo de álcool, obesidade, hipertensão, diabetes e cardiopatia, cerca de 10% dos indivíduos com idade igual ou superior a 80 anos e algo em torno de 25% daqueles com idade igual ou superior a 90 anos terão fibrilação atrial1. Essas taxas aumentam substancialmente quando se agregam a fatores de risco isolados ou combinados. A despeito da sua já bem conhecida relação com a ocorrência do acidente vascular encefálico trombo-embólico2, a presença de fibrilação atrial tem sido identificada como um fator de risco de mortalidade independente em grandes estudos populacionais3.

Reflections on CABANA Trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial)

Atrial fibrillation has been consolidated in recent decades as a serious public health problem, considering its notorious increase in prevalence with aging combined with increased population survival. Data from the Framingham Heart Study indicate that, even in an optimal scenario of absence of classic risk factors for its occurrences, such as smoking, alcohol abuse, obesity, hypertension, diabetes, and heart disease, about 10% of individuals aged 80 or over and about 25% of those aged 90 or over will have atrial fibrillation. These rates substantially increase when added to single or combined risk factors. Despite its already well-known association with the occurrence of thromboembolic stroke, the presence of atrial fibrillation has been identified as an independent mortality risk factor in large population studies.

Incidence of atrial fibrillation among patients with an embolic stroke of undetermined source: Insights from insertable cardiac monitors

Background Prophylactic use of direct oral anticoagulants for recurrent stroke prevention in patients with embolic strokes of undetermined source is currently being investigated. It is uncertain whether the bleeding risks associated with prophylactic direct oral anticoagulants use will outweigh any stroke prevention benefit in embolic strokes of undetermined source patients who lack underlying atrial fibrillation. Methods We determined the proportion of cryptogenic stroke patients in the CRYSTAL atrial fibrillation trial who met inclusion criteria for the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials and their atrial fibrillation incidence. Both embolic strokes of undetermined source trials impose requirements on age, modified Rankin Score, antiplatelet use, and type of infarction. Insertable cardiac monitors were used to determine the atrial fibrillation detection rates at 30 days and 3 years using Kaplan–Meier’s estimates. Results Among 441 patients enrolled in the CRYSTAL atrial fibrillation trial, 189 (42.9%) and 236 (53.5%) met the inclusion criteria of the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials, respectively. Atrial fibrillation detection rates at 3 years among insertable cardiac monitors patients eligible for the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials were 35.8% and 33.6% while detection rates at 30 days were 5.6% and 3.5%, respectively. Conclusion Only half of cryptogenic stroke patients in CRYSTAL atrial fibrillation met the inclusion criteria for the ongoing embolic strokes of undetermined source trials. Approximately, two-thirds of patients with embolic strokes of undetermined source do not have any atrial fibrillation despite continuous rhythm monitoring for up to three years. The benefits of prophylactic use of direct oral anticoagulants in the absence of atrial fibrillation is unknown and therefore embolic strokes of undetermined source patients could benefit from prolonged atrial fibrillation monitoring until more robust data are available. ClinicalTrials.gov Registration NCT00924638. https://clinicaltrials.gov/ct2/show/NCT00924638 .