Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data

OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up.Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION ClinicalTrials.gov NCT01090362

Relationship between the Renal Function and Adverse Clinical Events in Patients with Atrial Fibrillation: A Japanese Multicenter Registry Substudy

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, but the real-world data after approval of direct oral anticoagulants (DOACs) are still lacking in Japan. We investigated the association of the baseline renal function and adverse clinical events and risk of adverse clinical events with DOACs compared to warfarin for each renal functional level in Japanese AF patients. Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter observational registry (median follow-up period: 39 months). The creatinine clearance (CrCl) values were estimated by the Cockcroft–Gault formula, and divided into normal renal function, and mild and moderate-severe CKD (CrCl ≥ 80, 50–79, &lt;50 mL/min). Results: In the SAKURA AF Registry, the baseline CrCl data were available for 3242 patients (52% for DOAC and 48% for warfarin user). The relative risk of adverse clinical events was significantly higher in the patients with a CrCl &lt; 50 mL/min as compared to those with a CrCl ≥ 80 mL/min (adjusted HRs: 2.53 for death, 2.53 for cardiovascular [CV] events, 2.13 for strokes, and 1.83 for major bleeding). Risks of all adverse clinical events were statistically even between DOAC and warfarin users for each renal function level. Conclusion: Moderate–severe CKD was associated with a higher mortality, CV events, strokes, and major bleeding than normal renal function. The safety and effectiveness of DOACs over warfarin were similar for each renal function level. By a worsening renal function, the incidence of adverse clinical events increased, especially deaths and CV events as compared to strokes and major bleeding.</jats:p

Current use of direct oral anticoagulants for atrial fibrillation in Japan: Findings from the SAKURA AF Registry

Background: Large-scale investigations on the use of oral anticoagulants including direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) have not included Japanese patients. Methods: We established the multicenter SAKURA AF Registry to support prospective observational research on the status of anticoagulation treatment, especially with DOAC, for AF in Japan. We enrolled 3266 AF patients treated with warfarin (n=1577) or any of 4 DOACs (n=1689) from 63 institutions (2 cardiovascular centers, 13 affiliated hospitals or community hospitals, and 48 private clinics) in the Tokyo area. Results: We conducted our first analysis of the registry data, and although we found equivalent mean age between the DOAC and warfarin users (71.8±9.5 vs. 72.3±9.4 years, p=0.2117), we found a slightly lower risk of stroke (CHADS2 score of 0 or 1 [46.9% vs. 39.4%, p<0.0001]) and significantly better creatinine clearance in DOAC users (70.4±27 vs. 65.6±25.7 mL/min, p<0.0001). Importantly, we documented under-dosing in 32% of warfarin users and inappropriate-low-dosing in 19.7–27.6% of DOAC users. Conclusions: Our initial analysis of the SAKURA AF Registry data clarified the real-world use of anticoagulants, which includes DOACs and warfarin in Japan. The DOAC users were at a lower risk for stroke than the warfarin users. In 20–30% of DOAC users, the dose was inappropriately reduced

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index &lt; 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index &lt; 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p &lt; 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p &lt; 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31–2.25) and all-cause mortality (HR 1.43; 95% CI 1.06–1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p &lt; 0.05), net reclassification improvement (all p &lt; 0.001), and integrated discrimination improvement (all p &lt; 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p &lt; 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.</jats:p

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index &lt; 1.75, n = 1022), second tertile (1.75 &le; FIB4 index &lt; 2.51, n = 1022), and third tertile (FIB4 index &ge; 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p &lt; 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p &lt; 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31&ndash;2.25) and all-cause mortality (HR 1.43; 95% CI 1.06&ndash;1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p &lt; 0.05), net reclassification improvement (all p &lt; 0.001), and integrated discrimination improvement (all p &lt; 0.001). A FIB4 index &ge; 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p &lt; 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients