Age-Related Clinical Outcomes of Patients with Non-Valvular Atrial Fibrillation: Insights from the COOL-AF Registry

Figures & data

Table 1 Baseline Characteristics of All Patients, and Compared Between Patients Aged <65, 65–74 and ≥75 Years

Variables	All (N=3402)	Age <65 (n=1329)	Age 65–74 (n=1094)	Age ≥75 (n=979)	p-value
Age (years)	67.4±11.3	56.10±7.14	69.49±2.89	80.32±4.24	<0.001^a,b,c
Female gender	1422 (41.8%)	463 (34.8%)	469 (42.9%)	490 (50.1%)	<0.001^a,b,c
Time after diagnosis of AF (years)	3.36±4.325	2.79±3.43	3.74±4.81	3.70±4.75	<0.001^a,b
Atrial fibrillation					0.001^b
– Paroxysmal	1148 (33.7%)	490 (36.9%)	371 (33.9%)	287 (29.3%)
– Persistent	643 (18.9%)	257 (19.3%)	205 (18.7%)	181 (18.5%)
– Permanent	1611 (47.4%)	582 (43.8%)	518 (47.3%)	511 (52.2%)
Symptomatic AF	2618 (77.0%)	1065(80.1%)	824 (75.3%)	729 (74.5%)	0.002^a,b
History of heart failure	912 (26.8%)	378 (28.4%)	278 (25.4%)	256 (26.1%)	0.211
History of coronary artery disease	547 (16.1%)	161 (12.1%)	205 (18.7%)	181 (18.5%)	<0.001^a,b
Cardiac implantable electronic device	341 (10.0%)	76 (5.7%)	120 (11.0%)	145 (14.8%)	<0.001^a,b,c
History of ischemic stroke/TIA	592 (17.4%)	189 (14.2%)	187 (17.1%)	216 (22.1%)	<0.001^a,c
Hypertension	2328 (68.4%)	759 (57.1%)	792 (72.4%)	777 (79.4%)	<0.001^a,b,c
Diabetes mellitus	839 (24.7%)	316 (23.8%)	298 (27.2%)	225 (23.0%)	0.051
Smoking	678 (19.9%)	298 (22.4%)	220 (20.1%)	160 (16.3%)	0.001^b
Dyslipidemia	1915 (56.3%)	661 (49.7%)	679 (62.1%)	575 (58.7%)	<0.001^a,b
Renal replacement therapy	40 (1.2%)	14 (1.1%)	17 (1.6%)	9 (0.9%)	0.355
Dementia	29 (0.9%)	6 (0.5%)	8 (0.7%)	15 (1.5%)	0.018^b
CKD	2051 (60.3%)	510 (38.4%)	726 (66.4%)	815 (83.2%)	<0.001^a,b,c
History of bleeding	323 (9.5%)	90 (6.8%)	113 (10.3%)	120 (12.3%)	<0.001^a,b
CHA2DS2-VASc score					<0.001^a
– 0	196 (5.8%)	196 (14.7%)	0 (0.0%)	0 (0.0%)
– 1	422 (12.4%)	371 (27.9%)	51 (4.7%)	0 (0.0%)
– ≥2	2784 (81.8%)	762 (57.3%)	1043(95.3%)	979 (100.0%)
HAS-BLED score					<0.001^a
– 0	490 (14.4%)	484 (36.4%)	6 (0.5%)	0 (0.0%)
– 1–2	2373 (69.8%)	798 (60.0%)	839 (76.7%)	736 (75.2%)
– ≥3	539 (15.8%)	47 (3.5%)	249 (22.8%)	243 (24.8%)
Antiplatelet	890 (26.2%)	366 (27.5%)	293 (26.8%)	231 (23.6%)	0.088
Anticoagulant	2566 (75.4%)	880 (66.2%)	887 (81.1%)	799 (81.6%)	<0.001^a,b
– Warfarin	2338 (68.7%)	795 (59.8%)	811 (74.1%)	732 (74.8%)	<0.001^a,b
– NOACs	228 (6.7%)	85 (6.4%)	76 (6.9%)	67 (6.8%)	0.845

Notes: ^aStatistical significant (p <0.05) age <65 vs age 65–74. ^bStatistical significant (p <0.05) age <65 vs age ≥75. ^cStatistical significant (p <0.05) age 65–74 vs age ≥75. Data presented as mean ± standard deviation or number and percentage.

Abbreviations: AF, atrial fibrillation; TIA, transient ischemic attack; NOACs, non-vitamin K antagonist oral anticoagulants.

A p-value <0.05 indicates statistical significance (bold).

Table 2 Incidence Rate of Clinical Outcomes According to Age Group

Age Group	Number of Patients	Number of Events	Follow-Up Time (×100 Person-Years)	Incidence Rate per 100 Person-Years (95% CI)
Ischemic stroke/TIA
Age <65 y	1329	19	28.39	0.67 (0.40–1.04)
Age 65–74 y	1094	33	23.61	1.40 (0.96–1.96)
Age ≥75 y	979	51	19.93	2.56 (1.91–3.37)
Major bleeding
Age <65 y	1329	26	28.39	0.92 (0.60–1.34)
Age 65–74 y	1094	57	23.61	2.41 (1.83–3.13)
Age ≥75 y	979	69	19.93	3.46 (2.70–4.39)
ICH
Age <65 y	1329	7	28.39	0.25 (0.10–0.51)
Age 65–74 y	1094	18	23.61	0.76 (0.45–1.21)
Age ≥75 y	979	25	19.93	1.25 (0.81–1.85)
Heart failure
Age <65 y	1329	58	28.39	2.04 (1.55–2.64)
Age 65–74 y	1094	76	23.61	3.22 (2.54–4.03)
Age ≥75 y	979	84	19.93	4.22 (3.37–5.23)
Death
Age <65 y	1329	52	28.39	1.83 (1.37–2.40)
Age 65–74 y	1094	79	23.61	3.35 (2.65–4.17)
Age ≥75 y	979	140	19.93	7.03 (5.92–8.30)

Abbreviations: CI, confidence interval; TIA, transient ischemic attack; ICH, intracerebral hemorrhage.

Table 3 Incidence Rate of Ischemic Stroke/TIA According to Age Group and CHA₂DS₂-VASc Score

Age Group	Number of Patients	Number of Events	Follow-Up Time (×100 Person-Years)	Incidence Rate per 100 Person-Years (95% CI)
All patients
All	3402	103	71.93	1.43
CHA2DS2-VASc 0	196	3	4.04	0.74
CHA2DS2-VASc 1	422	5	8.90	0.56
CHA2DS2-VASc ≥2	2784	95	58.99	1.61
Age <65
All	1329	19	28.39	0.67
CHA2DS2-VASc 0	196	3	4.04	0.74
CHA2DS2-VASc 1	371	4	7.83	0.51
CHA2DS2-VASc ≥2	762	12	16.52	0.73
Age 65–74
All	1094	33	23.61	1.40
CHA2DS2-VASc 0	0	0	0.00	–
CHA2DS2-VASc 1	51	1	1.07	0.94
CHA2DS2-VASc ≥2	1043	32	22.54	1.42
Age ≥75
All	979	51	19.93	2.56
CHA2DS2-VASc 0	0	0	0.00	–
CHA2DS2-VASc 1	0	0	0.00	–
CHA2DS2-VASc ≥2	979	51	19.93	2.56

Figure 1 Incidence rate of ischemic stroke (IS)/transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death compared between patients aged <65, 65–74, and ≥75 years.

Figure 2 Forest plot of unadjusted and adjusted hazard ratios and their 95% confidence intervals for ischemic stroke/transient ischemic attack (TIA), major bleeding, intracerebral hemorrhage (ICH), heart failure, and death in patients aged 65–74, and ≥75 years as compared to those aged <65 years (<65 years was used as a reference).

Figure 3 Cumulative event rate for ischemic stroke/transient ischemic attack (TIA), major bleeding, intracerebral hemorrhage (ICH), and death over time compared between patients aged <65, 65–74, and ≥75 years.  A-C: unadjusted analysis. D-F: analysis adjusted for confounders.

Figure 4 Cubic spline graph of adjusted hazard ratio (blue line) and 95% confidence interval (purple shaded area) (Y-axis) relative to age (X-axis) for (A) ischemic stroke/transient ischemic attack (TIA), (B) major bleeding, (C) intracerebral hemorrhage (ICH), and (D) death.

Figure 5 Rate of ischemic stroke (IS)/transient ischemic attack (TIA), major bleeding, and intracerebral hemorrhage (ICH) according to age and oral anticoagulant (OAC) status (A), and according to age compared between warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) (B). Net clinical benefit (NCB) and 95% confidence interval (CI) according to age compared between OAC and no OAC, and between NOAC and warfarin (C).