Table 5.
Serious adverse events, cardiovascular and thromboembolic disorders, hypertension, and gastrointestinal ulceration and hemorrhage by low-dose aspirin (ASA) at baseline*
| Adverse events | Median time at risk, mo | Events/participants |
Event rate/1000 person-years (95% CI) |
HR (95% CI), P | LRT Pinteraction | ||
|---|---|---|---|---|---|---|---|
| Placebo | Celecoxib | Placebo | Celecoxib | ||||
| Serious adverse events | |||||||
| Intention-to-treat analysis† | |||||||
| Overall (n = 824) | 29.6 | 93/410 | 104/414 | 100.8 (82.3 to 123.5) | 112.8 (93.1 to 136.7) | 1.13 (0.85 to 1.49), .40 | |
| Yes ASA (n = 401) | 29.6 | 52/199 | 53/202 | 113.4 (86.4 to 148.8) | 121.5 (92.8 to 159.0) | 1.06 (0.72 to 1.56), .76 | |
| No ASA (n = 423) | 29.4 | 41/211 | 51/212 | 88.4 (65.1 to 120.1) | 105.0 (79.8 to 138.1) | 1.20 (0.80 to 1.82), .38 | .66 |
| While on intervention‡ | |||||||
| Overall (n = 798) | 13.2 | 41/397 | 53/401 | 86.9 (64.0 to 118.0) | 112.5 (86.0 to 147.3) | 1.29 (0.86 to 1.94), .22 | |
| Yes ASA (n = 393) | 13.4 | 22/196 | 30/197 | 95.5 (62.9 to 145.0) | 131.3 (91.8 to 187.8) | 1.36 (0.78 to 2.37), .27 | |
| No ASA (n = 405) | 13.1 | 19/201 | 23/204 | 78.7 (50.2 to 123.4) | 94.8 (63.0 to 142.7) | 1.20 (0.65 to 2.21), .55 | .77 |
| After intervention cessation§ | |||||||
| Overall (n = 679) | 12.2 | 57/336 | 60/343 | 121.7 (93.9 to 157.7) | 127.8 (99.2 to 164.6) | 1.06 (0.73 to 1.52), .77 | |
| Yes ASA (n = 328) | 12.3 | 31/165 | 28/163 | 131.0 (92.1 to 186.3) | 126.9 (87.6 to 183.8) | 0.96 (0.57 to 1.60), .87 | |
| No ASA (n = 351) | 11.5 | 26/171 | 32/180 | 112.2 (76.4 to 164.7) | 128.6 (90.9 to 181.8) | 1.15 (0.68 to 1.94), .60 | .59 |
| Serious adverse cardiovascular and thromboembolic disorders | |||||||
| Intention-to-treat analysis† | |||||||
| Overall (n = 824) | 31.4 | 38/410 | 35/414 | 37.5 (27.3 to 51.6) | 34.2 (24.5 to 47.6) | 0.93 (0.59 to 1.47), .75 | |
| Yes ASA (n = 401) | 31.5 | 26/199 | 20/202 | 52.3 (35.6 to 76.8) | 41.8 (27.0 to 64.8) | 0.78 (0.43 to 1.40), .40 | |
| No ASA (n = 423) | 31.4 | 12/211 | 15/212 | 23.3 (13.2 to 41.0) | 27.5 (16.6 to 45.6) | 1.17 (0.54 to 2.51), .69 | .35 |
| While on intervention‡ | |||||||
| Overall (n = 798) | 14.6 | 18/397 | 22/401 | 36.8 (23.2 to 58.3) | 44.2 (29.1 to 67.1) | 1.18 (0.63 to 2.20), .60 | |
| Yes ASA (n = 393) | 14.2 | 13/196 | 14/197 | 55.2 (32.0 to 95.0) | 58.5 (34.7 to 98.8) | 1.03 (0.48 to 2.20), .93 | |
| No ASA (n = 405) | 15.0 | 5/201 | 8/204 | 19.7 (8.2 to 47.3) | 30.9 (15.5 to 61.9) | 1.63 (0.53 to 4.99), .40 | .52 |
| After intervention cessation§ | |||||||
| Overall (n = 679) | 13.6 | 20/336 | 16/343 | 39.1 (25.2 to 60.6) | 31.0 (19.0 to 50.6) | 0.78 (0.40 to 1.51), .46 | |
| Yes ASA (n = 328) | 13.6 | 13/165 | 8/163 | 50.3 (29.2 to 86.7) | 33.2 (16.6 to 66.4) | 0.62 (0.26 to 1.49), .28 | |
| No ASA (n = 351) | 13.5 | 7/171 | 8/180 | 27.6 (13.2 to 57.9) | 29.1 (14.5 to 58.1) | 0.98 (0.34 to 2.79), .97 | .47 |
| Cardiovascular and thromboembolic disorders∥ | |||||||
| Intention-to-treat analysis† | |||||||
| Overall (n = 824) | 30.7 | 71/410 | 65/414 | 73.0 (57.7 to 92.5) | 67.1 (52.7 to 85.6) | 0.91 (0.65 to 1.28), .58 | |
| Yes ASA (n = 401) | 30.9 | 46/199 | 38/202 | 100.5 (75.3 to 134.2) | 85.1 (61.9 to 116.9) | 0.85 (0.55 to 1.31), .46 | |
| No ASA (n = 423) | 30.4 | 25/211 | 27/212 | 47.2 (31.4 to 71.0) | 51.8 (35.5 to 75.5) | 1.03 (0.60 to 1.78), .91 | .57 |
| While on intervention‡ | |||||||
| Overall (n = 798) | 13.8 | 39/397 | 40/401 | 81.4 (59.5 to 111.4) | 83.2 (61.0 to 113.4) | 1.01 (0.65 to 1.57), .96 | |
| Yes ASA (n = 393) | 13.4 | 30/196 | 25/197 | 132.1 (92.3 to 188.9) | 109.4 (73.9 to 161.9) | 0.81 (0.47 to 1.37), .43 | |
| No ASA (n = 405) | 14.5 | 9/201 | 15/204 | 35.7 (18.6 to 68.6) | 59.5 (35.9 to 98.7) | 1.68 (0.73 to 3.83), .22 | .15 |
| After intervention cessation§ | |||||||
| Overall (n = 679) | 12.6 | 35/336 | 31/343 | 71.8 (51.6 to 100.0) | 61.6 (43.3 to 87.6) | 0.86 (0.53 to 1.39), .53 | |
| Yes ASA (n = 328) | 12.5 | 20/165 | 16/163 | 80.5 (51.9 to 124.8) | 68.7 (42.1 to 112.1) | 0.85 (0.43 to 1.65), .62 | |
| No ASA (n = 351) | 12.7 | 15/171 | 15/180 | 62.8 (37.8 to 104.1) | 55.5 (33.5 to 92.1) | 0.84 (0.40 to 1.74), .63 | .96 |
| Hypertension | |||||||
| Intention-to-treat analysis† | |||||||
| Overall (n = 824) | 31.0 | 43/410 | 55/414 | 43.3 (32.1 to 58.3) | 57.8 (44.4 to 75.3) | 1.34 (0.90 to 1.99), .16 | |
| Yes ASA (n = 401) | 31.2 | 21/199 | 29/202 | 42.2 (27.5 to 64.7) | 64.9 (45.1 to 93.3) | 1.49 (0.85 to 2.62), .17 | |
| No ASA (n = 423) | 30.8 | 22/211 | 26/212 | 44.4 (29.2 to 67.4) | 51.6 (35.1 to 75.8) | 1.16 (0.66 to 2.05), .61 | .51 |
| While on intervention‡ | |||||||
| Overall (n = 798) | 13.3 | 20/397 | 34/401 | 41.7 (26.9 to 64.7) | 71.3 (51.0 to 99.8) | 1.72 (0.99 to 2.98), .06 | |
| Yes ASA (n = 393) | 13.5 | 8/196 | 18/197 | 33.7 (16.9 to 67.4) | 78.1 (49.2 to 123.9) | 2.33 (1.01 to 5.37), .05 | |
| No ASA (n = 405) | 13.0 | 12/201 | 16/204 | 49.6 (28.2 to 87.3) | 65.0 (39.8 to 106.1) | 1.28 (0.61 to 2.71), .51 | .28 |
| After intervention cessation∥ | |||||||
| Overall (n = 679) | 12.8 | 20/336 | 21/343 | 39.4 (25.4 to 61.1) | 42.6 (27.8 to 65.4) | 1.09 (0.59 to 2.00), .79 | |
| Yes ASA (n = 328) | 12.8 | 10/165 | 11/163 | 38.6 (20.8 to 71.8) | 47.7 (26.4 to 86.1) | 1.19 (0.50 to 2.83), .69 | |
| No ASA (n = 351) | 12.8 | 10/171 | 10/180 | 40.3 (21.7 to 74.8) | 38.2 (20.6 to 71.0) | 0.94 (0.39 to 2.26), .89 | .72 |
| Gastrointestinal ulceration and hemorrhage | |||||||
| Intention-to-treat analysis† | |||||||
| Overall (n = 824) | 31.6 | 16/410 | 20/414 | 15.5 (9.5 to 25.4) | 19.6 (12.6 to 30.4) | 1.26 (0.65 to 2.43), .50 | |
| Yes ASA (n = 401) | 31.8 | 7/199 | 14/202 | 13.5 (6.4 to 28.4) | 29.0 (17.2 to 49.0) | 2.08 (0.84 to 5.17), .11 | |
| No ASA (n = 423) | 31.4 | 9/211 | 6/212 | 17.6 (9.2 to 33.8) | 11.1 (5.0 to 24.8) | 0.61 (0.22 to 1.74), .36 | .09 |
| While on intervention‡ | |||||||
| Overall (n = 798) | 14.5 | 8/397 | 13/401 | 16.2 (8.1 to 32.4) | 26.3 (15.3 to 45.3) | 1.59 (0.66 to 3.84), .30 | |
| Yes ASA (n = 393) | 14.5 | 4/196 | 10/197 | 16.7 (6.3 to 44.4) | 41.6 (22.4 to 77.3) | 2.48 (0.78 to 7.95), .13 | |
| No ASA (n = 405) | 14.7 | 4/201 | 3/204 | 15.8 (5.9 to 42.0) | 11.8 (3.8 to 36.6) | 0.73 (0.16 to 3.28), .69 | .21 |
| After intervention cessation§ | |||||||
| Overall (n = 679) | 13.6 | 7/336 | 6/343 | 13.4 (6.4 to 28.0) | 11.6 (5.2 to 25.9) | 0.87 (0.29 to 2.61), .81 | |
| Yes ASA (n = 328) | 14.4 | 3/165 | 3/163 | 11.2 (3.6 to 34.7) | 12.3 (4.0 to 38.1) | 1.17 (0.23 to 5.87), .85 | |
| No ASA (n = 351) | 13.4 | 4/171 | 3/180 | 15.6 (5.9 to 41.7) | 11.0 (3.6 to 34.2) | 0.69 (0.15 to 3.14), .64 | .68 |
*Two-sided Cox regression model adjusted for random assignment to selenium, aspirin use (unless stratified), and clinic. ASA = aspirin; CI = confidence interval; HR = hazard ratio; LRT = two-sided likelihood ratio test.
†Time at risk from random assignment to study withdrawal.
‡Time at risk from the second day after participant received the intervention until 14 days after intervention cessation.
§Time at risk from 15 days after intervention cessation until study withdrawal.
∥Two participants, both randomized to placebo, experienced a cardiovascular/thromboembolic event on the date of random assignment (time = 0). These two participants are included in the event counts but not included in the rate calculations or the Cox models because they had no time-at-risk to contribute.