Treatment-emergent cardiovascular events
| Category (preferred term), n (%) . | ASPEN cohort 1 WM . | ALPINE R/R CLL/SLL . | Pooled ASPEN/ALPINE . | Pooled analysis B-cell malignancies . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zanubrutinib (n = 101) . | Ibrutinib (n = 98) . | Zanubrutinib (n = 324) . | Ibrutinib (n = 324) . | Zanubrutinib (N = 425) . | Ibrutinib (N = 422) . | Zanubrutinib (N = 1550) . | ||||||||
| Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | |
| Any cardiovascular event | 23 (22.8) | 12 (11.9) | 41 (41.8) | 26 (26.5) | 91 (28.1) | 56 (17.3) | 106 (32.7) | 59 (18.2) | 114 (26.8) | 68 (16.0) | 147 (34.8) | 85 (20.1) | 324 (20.9) | 161 (10.4) |
| Atrial fibrillation/ flutter | 9 (8.9) | 2 (2.0) | 23 (23.5) | 8 (8.2) | 17 (5.2) | 8 (2.5) | 43 (13.3) | 13 (4.0) | 26 (6.1) | 10 (2.4) | 66 (15.6) | 21 (5.0) | 75 (4.8) | 31 (2.0) |
| Atrial fibrillation | 8 (7.9) | 2 (2.0) | 21 (21.4) | 6 (6.1) | 15 (4.6) | 6 (1.9) | 40 (12.3) | 12 (3.7) | 23 (5.4) | 8 (1.9) | 61 (14.5) | 18 (4.3) | 69 (4.5) | 27 (1.7) |
| Atrial flutter | 1 (1.0) | 0 | 4 (4.1) | 2 (2.0) | 2 (0.6) | 2 (0.6) | 3 (0.9) | 1 (0.3) | 3 (0.7) | 2 (0.5) | 7 (1.7) | 3 (0.7) | 7 (0.5) | 5 (0.3) |
| Symptomatic ventricular arrhythmia∗ | 0 | 0 | 1 (1.0) | 0 | 3 (0.9) | 0 | 6 (1.9)† | 4 (1.2) | 3 (0.7) | 0 | 7 (1.7)† | 4 (0.9) | 11 (0.7) | 6 (0.4) |
| Ventricular arrhythmia | 0 | 0 | 1 (1.0) | 0 | 2 (0.6) | 0 | 1 (0.3) | 0 | 2 (0.5) | 0 | 2 (0.5) | 0 | 4 (0.3) | 1 (0.1) |
| Ventricular extrasystoles | 0 | 0 | 0 | 0 | 1 (0.3) | 0 | 1 (0.3) | 0 | 1 (0.2) | 0 | 1 (0.2) | 0 | 3 (0.2) | 1 (0.1) |
| Cardiac arrest | 0 | 0 | 0 | 0 | 0 | 0 | 3 (0.9) | 3 (0.9)‡ | 0 | 0 | 3 (0.7) | 3 (0.7)‡ | 2 (0.1) | 2 (0.1) |
| Pulseless electrical activity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |
| Ventricular tachycardia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |
| Ventricular fibrillation | 0 | 0 | 0 | 0 | 0 | 0 | 2 (0.6) | 2 (0.6) | 0 | 0 | 2 (0.5) | 2 (0.5) | 0 | 0 |
| Hypertension | 17 (16.8) | 10 (9.9) | 25 (25.5) | 20 (20.4) | 76 (23.5) | 49 (15.1) | 74 (22.8) | 44 (13.6) | 93 (21.9) | 59 (13.9) | 99 (23.5) | 64 (15.2) | 259 (16.7) | 129 (8.3) |
| Hypertension | 17 (16.8) | 10 (9.9) | 24 (24.5) | 19 (19.4) | 71 (21.9) | 48 (14.8) | 64 (19.8) | 36 (11.1) | 88 (20.7) | 58 (13.6) | 88 (20.9) | 55 (13.0) | 242 (15.6) | 125 (8.1) |
| Blood pressure increased | 0 | 0 | 1 (1.0) | 1 (1.0) | 7 (2.2) | 4 (1.2) | 14 (4.3) | 10 (3.1) | 7 (1.6) | 4 (0.9) | 15 (3.6) | 11 (2.6) | 16 (1.0) | 6 (0.4) |
| Hypertensive crisis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 (0.3) | 1 (0.1) |
| Essential hypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 0 |
| Prehypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 0 |
| Systolic hypertension | 0 | 0 | 0 | 0 | 1 (0.3) | 0 | 0 | 0 | 1 (0.2) | 0 | 0 | 0 | 1 (0.1) | 0 |
| Hypertensive heart disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |
| Category (preferred term), n (%) . | ASPEN cohort 1 WM . | ALPINE R/R CLL/SLL . | Pooled ASPEN/ALPINE . | Pooled analysis B-cell malignancies . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zanubrutinib (n = 101) . | Ibrutinib (n = 98) . | Zanubrutinib (n = 324) . | Ibrutinib (n = 324) . | Zanubrutinib (N = 425) . | Ibrutinib (N = 422) . | Zanubrutinib (N = 1550) . | ||||||||
| Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | Any grade . | Grade ≥3 . | |
| Any cardiovascular event | 23 (22.8) | 12 (11.9) | 41 (41.8) | 26 (26.5) | 91 (28.1) | 56 (17.3) | 106 (32.7) | 59 (18.2) | 114 (26.8) | 68 (16.0) | 147 (34.8) | 85 (20.1) | 324 (20.9) | 161 (10.4) |
| Atrial fibrillation/ flutter | 9 (8.9) | 2 (2.0) | 23 (23.5) | 8 (8.2) | 17 (5.2) | 8 (2.5) | 43 (13.3) | 13 (4.0) | 26 (6.1) | 10 (2.4) | 66 (15.6) | 21 (5.0) | 75 (4.8) | 31 (2.0) |
| Atrial fibrillation | 8 (7.9) | 2 (2.0) | 21 (21.4) | 6 (6.1) | 15 (4.6) | 6 (1.9) | 40 (12.3) | 12 (3.7) | 23 (5.4) | 8 (1.9) | 61 (14.5) | 18 (4.3) | 69 (4.5) | 27 (1.7) |
| Atrial flutter | 1 (1.0) | 0 | 4 (4.1) | 2 (2.0) | 2 (0.6) | 2 (0.6) | 3 (0.9) | 1 (0.3) | 3 (0.7) | 2 (0.5) | 7 (1.7) | 3 (0.7) | 7 (0.5) | 5 (0.3) |
| Symptomatic ventricular arrhythmia∗ | 0 | 0 | 1 (1.0) | 0 | 3 (0.9) | 0 | 6 (1.9)† | 4 (1.2) | 3 (0.7) | 0 | 7 (1.7)† | 4 (0.9) | 11 (0.7) | 6 (0.4) |
| Ventricular arrhythmia | 0 | 0 | 1 (1.0) | 0 | 2 (0.6) | 0 | 1 (0.3) | 0 | 2 (0.5) | 0 | 2 (0.5) | 0 | 4 (0.3) | 1 (0.1) |
| Ventricular extrasystoles | 0 | 0 | 0 | 0 | 1 (0.3) | 0 | 1 (0.3) | 0 | 1 (0.2) | 0 | 1 (0.2) | 0 | 3 (0.2) | 1 (0.1) |
| Cardiac arrest | 0 | 0 | 0 | 0 | 0 | 0 | 3 (0.9) | 3 (0.9)‡ | 0 | 0 | 3 (0.7) | 3 (0.7)‡ | 2 (0.1) | 2 (0.1) |
| Pulseless electrical activity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |
| Ventricular tachycardia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |
| Ventricular fibrillation | 0 | 0 | 0 | 0 | 0 | 0 | 2 (0.6) | 2 (0.6) | 0 | 0 | 2 (0.5) | 2 (0.5) | 0 | 0 |
| Hypertension | 17 (16.8) | 10 (9.9) | 25 (25.5) | 20 (20.4) | 76 (23.5) | 49 (15.1) | 74 (22.8) | 44 (13.6) | 93 (21.9) | 59 (13.9) | 99 (23.5) | 64 (15.2) | 259 (16.7) | 129 (8.3) |
| Hypertension | 17 (16.8) | 10 (9.9) | 24 (24.5) | 19 (19.4) | 71 (21.9) | 48 (14.8) | 64 (19.8) | 36 (11.1) | 88 (20.7) | 58 (13.6) | 88 (20.9) | 55 (13.0) | 242 (15.6) | 125 (8.1) |
| Blood pressure increased | 0 | 0 | 1 (1.0) | 1 (1.0) | 7 (2.2) | 4 (1.2) | 14 (4.3) | 10 (3.1) | 7 (1.6) | 4 (0.9) | 15 (3.6) | 11 (2.6) | 16 (1.0) | 6 (0.4) |
| Hypertensive crisis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 (0.3) | 1 (0.1) |
| Essential hypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 0 |
| Prehypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 0 |
| Systolic hypertension | 0 | 0 | 0 | 0 | 1 (0.3) | 0 | 0 | 0 | 1 (0.2) | 0 | 0 | 0 | 1 (0.1) | 0 |
| Hypertensive heart disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.1) | 1 (0.1) |