Temporal changes in stroke and heart failure following first-time atrial fibrillation/flutter in patients under 65 years of age: A Danish nationwide study
Authors: Schak Nielsen L , Kofoed Petersen J , Due H , Westergaard L M , Lund Kristensen S , Schou M , Koeber L , Fosboel E , Oestergaard L 
Published: November 2023

Abstract

Background
The incidence of atrial fibrillation/flutter (AF) has increased throughout the past two decades - also for patients under 65 years of age. Whether this increment in patients with AF under 65 years of age also influences the subsequent incidence of ischaemic stroke (stroke) and heart failure (HF) is yet to be elucidated. This patient group are of special interest as this population often is considered at low risk of stroke.

Methods
Using Danish nationwide registries, we identified all patients from 18–65 years with a first-time AF-diagnosis in 2000-2018. The cohort was categorised according to calendar periods into five groups: 2000-200, 2003-2006, 2007-2010, 2011-2014, and 2015-2018. Crude incidence rate (IR) of stroke and HF per 1,000 person years (PY) were calculated. The cumulative incidence (CI) of stroke and HF during one year of follow-up was computed accounting for death as a competing risk. The reverse Kaplan-Meier estimator was used to examine mortality during one year follow-up. Multivariable Cox proportional hazard analysis was used to compare outcomes between calendar periods with 2000-2002 as comparative reference. Hazard ratios (HR) were reported with 95% confidence intervals (95% CI).

Results
In this study 51,137 patients were included; 6,911 (median age 56, 64.5% males, 22.0% on OAC) in 2000-2002, 9,964 (median age 58, 65.5% males, 26.4% on OAC) in 2003-2006, 11,538 (median age 58, 64.7% males, 23.9% on OAC) in 2007-2010, 11,764 (median age 58, 63.6% males, in 29.2% on OAC) in 2011-2014, and 10,960 (median age 56, 65.9% males, 39.5% on OAC) in 2015-2018.
For stroke, crude IR/1,000 PY [95% CI] declined through calendar time as seen in the Figure. The crude IR were 10.4 [8.0;13.5] in 2000-2002 and 6.3 [4.9;8.0] in 2015-2018 with corresponding CIs of 1.0%, 0.9%, 0.9%, 0.8%, and 0.6%, respectively (p-value for difference=0.08).
The corresponding adjusted HRs [95% CI] were 0.94 [0.66;1.35] for calendar period 2003-2006, 0.87 [0.61;1.24] for 2007-2010, 0.86 [0.61;1.23] for 2011-2014, and 0.61 [0.41;0.91] for 2015-2018 as compared with 2000-2002.
As seen in the Figure crude IR [95% CI] for HF were stagnant over time with 37.2 [32.4;42.8] in 2000-2002 and 38.3 [34.7;42.3] in 2015-2018 with corresponding CIs of 3.4%, 3.3%, 3.5%, 3.4%, and 3.3%, respectively (p-value for difference=0.89).
The corresponding adjusted HRs [95% CI] were 0.93 [0.79;1.10] for calendar period 2003-2006, 0.99 [0.84;1.17] for 2007-2010, 0.99 [0.84;1.16] for 2011-2014, and 1.02 [0.86;1.20] for 2015-2018 as compared with 2000-2002.
Mortality with one year of follow-up was 3.8%, 4.4%, 4.4%, 4.5%, and 3.7% in calendar period 1-5 respectively (p-value for difference=0.38).

Conclusion
From nationwide registries in patients with atrial fibrillation/flutter under 65 years of age, we found a stepwise decline in one-year rates of ischaemic stroke with more recent calendar periods. Heart failure and mortality incidence were stable across calendar time.Incidence rates of ischemic stroke