Article Figures & Data
- Figure 1
Kaplan-Meier curves of the efficacy and safety outcomes in patients with different ages.
- Table 1
Baseline characteristics of the patients stratified by age
Characteristics <65
(N=3251)65–80
(N=2755)≥80
(N=406)P value Median age—year 56.2±6.1 71.2±4.2 83.9±3.2 <0.0001 Female sex—no (%) 901 (27.7) 1072 (38.9) 197 (48.5) <0.0001 Han ethnicity—no (%) 3181 (97.9) 2702 (98.1) 399 (98.3) 0.74 Medical history—no (%) Hypertension 2338 (71.9) 2089 (75.8) 303 (74.6) 0.003 Diabetes mellitus 1046 (32.2) 889 (32.3) 107 (26.4) 0.049 Dyslipidaemia 1025 (31.5) 682 (24.8) 76 (18.7) <0.0001 Previous ischaemic stroke 590 (18.2) 673 (24.4) 87 (21.4) <0.0001 Previous TIA 48 (1.5) 36 (1.3) 4 (1.0) 0.67 Myocardial infarction 32 (1.0) 53 (1.9) 11 (2.7) 0.001 Current smoking—no (%) 1266 (38.9) 675 (24.5) 40 (9.9) <0.0001 Current drinking—no (%) 857 (26.4) 462 (16.8) 48 (11.8) <0.0001 CYP2C19 LOF allele carriers—no (%) 0.69 Intermediate metabolisers 2528 (77.8) 2161 (78.4) 312 (76.9) Poor metabolisers 723 (22.2) 594 (21.6) 94 (23.2) Median time to randomisation (IQR)—hour 14.3 (9.2–20.7) 13.6 (8.8–20.4) 12.8 (8.3–19.8) 0.007 Qualifying event—no (%) 0.87 Ischaemic stroke 2622 (80.7) 2208 (80.2) 328 (80.8) TIA 629 (19.4) 547 (19.9) 78 (19.2) Median NIHSS score in patients with qualifying ischaemic stroke (IQR) 2 (1–3) 2 (1–3) 2 (1–3) 0.46 Median ABCD2 score in patients with qualifying TIA (IQR) 4 (4–5) 4 (4–5) 4 (4–5) <0.0001 Previous antiplatelet therapy—no (%) 318 (9.8) 376 (13.7) 54 (13.3) <0.0001 Previous lipid-lowering therapy—no (%) 209 (6.4) 249 (9.0) 41 (10.1) 0.0002 Symptomatic intracranial artery stenosis 737 (24.6) 759 (29.7) 143 (38.8) <0.0001 Symptomatic extracranial artery stenosis 104 (3.5) 142 (5.6) 25 (6.8) 0.0001 LOF, loss-of-function; NIHSS, National Institutes of Health Stroke Scale; TIA, transient ischaemic attack.
- Table 2
Baseline characteristics of the patients stratified by age and ticagrelor-aspirin versus clopidogrel-aspirin
Characteristics <65 (N=3251) 65–80
(N=2755)≥80 (N=406) T-A group
(n=1602)C-A group
(n=1649)P value T-A group
(n=1396)C-A group
(n=1359)P value T-A group
(n=207)C-A group
(n=199)P value Median age—year 56.1±6.1 56.2±6.1 0.77 71.3±4.3 71.1±4.1 0.31 83.8±3.4 83.9±2.9 0.25 Female sex—no (%) 453 (28.3) 448 (27.2) 0.48 539 (38.6) 533 (39.2) 0.74 98 (47.3) 99 (49.8) 0.63 Han ethnicity—no (%) 1569 (97.9) 1612 (97.8) 0.72 1372 (98.3) 1330 (97.9) 0.43 203 (98.1) 196 (98.5) 0.74 Medical history—no (%) Hypertension 1145 (71.5) 1193 (72.4) 0.58 1056 (75.6) 1033 (76.0) 0.82 155 (74.9) 148 (74.4) 0.91 Diabetes mellitus 526 (32.8) 520 (31.5) 0.43 443 (31.7) 446 (32.8) 0.54 64 (30.9) 43 (21.6) 0.03 Dyslipidaemia 513 (32.0) 512 (31.1) 0.55 335 (24.0) 347 (25.5) 0.35 40 (19.3) 36 (18.1) 0.75 Previous ischaemic stroke 289 (18.0) 301 (18.3) 0.87 342 (24.5) 331 (24.4) 0.93 38 (18.4) 49 (24.6) 0.12 Previous TIA 25 (1.6) 23 (1.4) 0.70 21 (1.5) 15 (1.1) 0.35 0 (0.0) 4 (2.0) 0.04 Myocardial infarction 21 (1.3) 11 (0.7) 0.06 28 (2.0) 25 (1.8) 0.75 5 (2.4) 6 (3.0) 0.71 Current smoking—no (%) 627 (39.1) 639 (38.8) 0.82 348 (24.9) 327 (24.1) 0.60 20 (9.7) 20 (10.1) 0.90 Current drinking—no (%) 417 (26.0) 440 (26.7) 0.67 238 (17.1) 224 (16.5) 0.69 33 (15.9) 15 (7.5) 0.009 CYP2C19 LOF allele carriers—no (%) 0.11 0.93 0.36 Intermediate metabolisers 1227 (76.6) 1301 (78.9) 1096 (78.5) 1065 (78.4) 163 (78.7) 149 (74.9) Poor metabolisers 375 (23.4) 348 (21.1) 300 (21.5) 294 (21.6) 44 (21.3) 50 (25.1) Median time to randomisation (IQR)—hour 14.0 (9.1–20.5) 14.6 (9.2–21.0) 0.26 13.4 (8.8–20.2) 14.0 (8.6–20.5) 0.66 12.2 (7.8–19.8) 13.1 (8.5–19.9) 0.24 Qualifying event—no (%) 0.53 0.62 0.85 Ischaemic stroke 1285 (80.2) 1337 (81.1) 1124 (80.5) 1084 (79.8) 168 (81.2) 160 (80.4) TIA 317 (19.8) 312 (18.9) 272 (19.5) 275 (20.2) 39 (18.8) 39 (19.6) Median NIHSS score in patients with qualifying ischaemic stroke (IQR) 2 (1–3) 2 (1–3) 0.45 2 (1–3) 2 (1–3) 0.70 2 (1–3) 2 (1–3) 0.88 Median ABCD2 score in patients with qualifying TIA (IQR) 4 (4–5) 4 (4–5) 0.45 4 (4–5) 4 (4–5) 0.35 4 (4–6) 4 (4–5) 0.29 Previous antiplatelet therapy—no (%) 158 (9.9) 160 (9.7) 0.88 206 (14.8) 170 (12.5) 0.09 21 (10.1) 33 (16.6) 0.06 Previous lipid-lowering therapy—no (%) 98 (6.1) 111 (6.7) 0.48 143 (10.2) 106 (7.8) 0.03 17 (8.2) 24 (12.1) 0.20 Symptomatic intracranial artery stenosis 374 (25.2) 363 (24.0) 0.45 387 (29.8) 372 (29.6) 0.92 80 (43.0) 63 (34.4) 0.09 Symptomatic extracranial artery stenosis 53 (3.6) 51 (3.4) 0.77 78 (6.0) 64 (5.1) 0.32 12 (6.5) 13 (7.1) 0.80 LOF, loss-of-function; NIHSS, National Institutes of Health Stroke Scale; TIA, transient ischaemic attack.
- Table 3
Efficacy and safety outcomes stratified by age
Outcomes Age n/N (%) HR/OR (95% CI)* Log-rank p value Efficacy outcomes Stroke <65 207/3251 (6.4) --- --- 65–80 188/2755 (6.8) 0.98 (0.79 to 1.20) 0.82 ≥80 39/406 (9.6) 1.39 (0.96 to 2.02) 0.08 Stroke within 30 days <65 172/3251 (5.3) --- --- 65–80 156/2755 (5.7) 1.01 (0.80 to 1.26) 0.96 ≥80 33/406 (8.1) 1.45 (0.97 to 2.18) 0.07 Ischaemic stroke <65 203/3251 (6.2) --- --- 65–80 186/2755 (6.8) 0.98 (0.80 to 1.21) 0.85 ≥80 38/406 (9.4) 1.37 (0.94 to 1.99) 0.10 Composite vascular events† <65 246/3251 (7.6) --- --- 65–80 229/2755 (8.3) 1.00 (0.83 to 1.21) 0.97 ≥80 47/406 (11.6) 1.41 (1.00 to 1.98) 0.048 Disabling stroke‡ <65 82/3251 (2.5) --- --- 65–80 78/2755 (2.8) 1.05 (0.76 to 1.46) 0.75 ≥80 29/406 (7.1) 2.43 (1.52 to 3.88) 0.0002 Safety outcomes Severe or moderate bleeding <65 7/3251 (0.2) --- --- 65–80 9/2755 (0.3) 1.78 (0.63 to 5.05) 0.28 ≥80 4/406 (1.0) 8.40 (1.95 to 36.21) 0.004 Any bleeding <65 138/3251 (4.2) --- --- 65–80 94/2755 (3.4) 0.81 (0.62 to 1.07) 0.14 ≥80 18/406 (4.4) 0.99 (0.59 to 1.68) 0.98 Intracranial haemorrhage <65 5/3251 (0.2) --- --- 65–80 2/2755 (0.1) 0.47 (0.08 to 2.72) 0.45 ≥80 2/406 (0.5) 2.86 (0.41 to 20.17) 0.29 Mortality <65 9/3251 (0.3) --- --- 65–80 12/2755 (0.4) 1.39 (0.55 to 3.50) 0.49 ≥80 6/406 (1.5) 7.56 (2.23 to 25.70) 0.001 *Adjusted for sex, medical history (hypertension, diabetes mellitus, dyslipidaemia, previous ischaemic stroke), current smoking and drinking, median time to randomisation, and previous antiplatelet therapy and lipid-lowering therapy.
†Composite vascular events included ischaemic stroke, haemorrhagic stroke, transient ischaemic stroke, myocardial infarction or death from vascular causes.
‡A stroke was defined as disabling if the patient had a modified Rankin scale score of >1.
- Table 4
Association of ticagrelor-aspirin versus clopidogrel-aspirin with efficacy and safety outcomes stratified by age
Outcomes Age Ticagrelor-aspirin group n/N (%) Clopidogrel-aspirin group n/N (%) HR/OR (95% CI)* Log-rank p value P interaction Efficacy outcomes Stroke <65 82/1602 (5.1) 125/1649 (7.6) 0.68 (0.51 to 0.91) 0.008 0.23 65–80 87/1396 (6.2) 101/1359 (7.4) 0.81 (0.60 to 1.09) 0.17 ≥80 22/207 (10.6) 17/199 (8.5) 1.00 (0.49 to 2.06) 0.99 Stroke within 30 days <65 68/1602 (4.2) 104/1649 (6.3) 0.67 (0.49 to 0.92) 0.01 0.33 65–80 69/1396 (4.9) 87/1359 (6.4) 0.75 (0.54 to 1.04) 0.09 ≥80 19/207 (9.2) 14/199 (7.0) 1.11 (0.50 to 2.48) 0.80 Ischaemic stroke <65 82/1602 (5.1) 121/1649 (7.3) 0.71 (0.53 to 0.94) 0.02 0.37 65–80 86/1396 (6.2) 100/1359 (7.4) 0.81 (0.60 to 1.09) 0.16 ≥80 21/207 (10.1) 17/199 (8.5) 0.94 (0.45 to 1.95) 0.86 Composite vascular events† <65 100/1602 (5.2) 146/1649 (8.9) 0.71 (0.55 to 0.92) 0.01 0.26 65–80 103/1396 (7.4) 126/1359 (9.3) 0.75 (0.58 to 0.99) 0.04 ≥80 26/207 (12.6) 21/199 (10.6) 0.93 (0.47 to 1.83) 0.83 Disabling stroke‡ <65 34/1602 (2.1) 48/1649 (2.9) 0.70 (0.45 to 1.10) 0.12 0.07 65–80 46/1396 (3.3) 32/1359 (2.4) 1.33 (0.83 to 2.12) 0.23 ≥80 17/207 (8.2) 12/199 (6.0) 1.00 (0.44 to 2.27) 0.99 Safety outcomes
0.65Severe or moderate bleeding <65 2/1602 (0.1) 5/1649 (0.3) 0.64 (0.10 to 4.03) 0.64 65–80 5/1396 (0.4) 4/1359 (0.3) 1.28 (0.30 to 5.48) 0.74 ≥80 2/207 (1.0) 2/199 (1.0) 0.80 (0.06 to 11.35) 0.87 Any bleeding <65 99/1602 (6.2) 39/1649 (2.4) 2.98 (2.02 to 4.40) <0.0001 0.04 65–80 63/1396 (4.5) 31/1359 (2.3) 1.95 (1.24 to 3.05) 0.004 ≥80 8/207 (3.9) 10/199 (5.0) 1.78 (0.48 to 6.66) 0.39 Intracranial haemorrhage <65 1/1602 (0.1) 4/1649 (0.2) 0.31 (0.03 to 2.96) 0.31 --- 65–80 1/1396 (0.1) 1/1359 (0.1) --- --- ≥80 1/207 (0.5) 1/199 (0.5) --- --- Mortality <65 3/1602 (0.2) 6/1649 (0.4) 0.27 (0.05 to 1.41) 0.12 0.98 65–80 4/1396 (0.3) 8/1359 (0.6) 0.79 (0.20 to 3.16) 0.73 ≥80 2/207 (1.0) 4/199 (2.0) 0.08 (0.01 to 1.37) 0.08 *Adjusted for sex, medical history (hypertension, diabetes mellitus, dyslipidaemia, previous ischaemic stroke), current smoking and drinking, median time to randomisation, and previous antiplatelet therapy and lipid-lowering therapy.
†Composite vascular events included ischaemic stroke, haemorrhagic stroke, transient ischaemic attack, myocardial infarction or death from vascular causes.
‡A stroke was defined as disabling if the patient had a modified Rankin scale score of >1.
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