Table 2.
Adverse event rates at 12- and 52-week follow-up following evolocumab, placebo or ezetimibe treatments
| Safety endpoints | Evolocumab (12 Week) | Placebo (12 Week) | Evolocumab versus Placebo (12 Week) | Ezetimibe (12 Week) | Evolocumab versus Ezetimibe (12 Week) | Evolocumab (52 Week) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pooled event rate (95 % CI) | Event/Total | Pooled event rate (95 % CI) | Event/Total | RR (95 % CI) | P value | Pooled event rate (95 % CI) | Event/Total | RR (95 % CI) | P value | Event/Total | |
| TEAE (Any) | 52.2 (44.8, 59.7) | 1472/3068 | 45.2 (40.6, 49.8) | 534/1240 | 1.07 (0.95, 1.21) | 0.260 | 54.7 (41.3, 68.0) | 278/554 | 0.92 (0.84, 1.01) | 0.074 | 78.4 (1047/1335) |
| TEAE (Serious) | 1.9 (1.4, 2.4) | 64/3068 | 1.2 (0.5, 1.9) | 23/1240 | 0.96 (0.60, 1.55) | 0.876 | 0.9 ( 0.3, 1.6) | 7/554 | 1.35 (0.61, 3.00) | 0.458 | 6.4 (85/1335) |
| Leading to discontinuation | 1.6 (0.9, 2.4) | 56/3068 | 1.1 (0.4, 1.8) | 21/1240 | 0.78 (0.46, 1.32) | 0.354 | 3.5 (1.0, 6.0) | 24/554 | 0.68 (0.42, 1.11) | 0.127 | 3.0 (40/1335) |
| Death | NA | 1/3068 | NA | 1/1240 | NA | NA | NA | 0/554 | NA | NA | 0.2 (3/1335) |
| CK >5 ULN | 0.5 (0.1, 0.8) | 16/2797 | 0.5 (0.2, 0.8) | 8/1150 | 0.57 (0.21, 1.51) | 0.258 | 0.5 (0, 0.8) | 4/509 | 0.55 (0.17, 1.81) | 0.325 | 1.0 (14/1335) |
| ALT or AST > 3 ULN | 0.2 (0.1, 0.4) | 12/2797 | 0.8 (0.3, 1.2) | 13/1150 | 0.43 (0.20, 0.93) | 0.033 | 0.7 (0.1, 1.3) | 4/509 | 0.43 (0.14, 1.34) | 0.147 | 1.3 (18/1335) |
| Adjudicated cardiovascular events | 0.6 (0.2, 1.1) | 20/2287 | 0.5 (0.1, 0.9) | 7/1014 | 1.07 (0.41, 2.76) | 0.892 | 0.9 (0, 1.9) | 2/266 | 0.50 (0.12, 2.13) | 0.346 | 1.1 (15/1335) |
| Musculoskeletal and connective-tissue disorders | 9.8 (4.1, 15.4) | 144/1397 | 7.1 (1.6, 12.6) | 39/508 | 1.08 (0.70, 1.67) | 0.738 | 6.1 (0.7, 11.5) | 13/231 | 1.10 (0.61, 2.00) | 0.751 | 9.2 (68/736) |
| Back pain | 2.6 (1.7, 3.4) | 56/2208 | 1.8 (0.7, 2.8) | 21/912 | 1.05 (0.53, 2.11) | 0.883 | 2.5 (0.9, 4.1) | 8/298 | 0.72 (0.34, 1.54) | 0.4 | 6.4 (85/1335) |
| Arthralgia | 1.7 (1.0, 2.5) | 35/1862 | 1.7 (0.9, 2.6) | 14/803 | 1.04 (0.56, 1.93) | 0.912 | 1.5 (0.2, 2.9) | 4/266 | 0.97 (0.35, 2.64) | 0.945 | 5.7 (76/1335) |
| Muscle spasms | 1.9 (0.7, 3.2) | 45/2193 | 1.3 (0.5, 2.0) | 11/803 | 1.02 (0.42, 2.49) | 0.963 | 2.5 (0.7, 4.3) | 13/400 | 0.67 (0.30, 1.50) | 0.335 | 2.3 (14/599) |
| Myalgia | 3.5 (1.5, 5.6) | 48/1382 | 1.0 (0.2, 1.8) | 5/399 | 1.13 (0.37, 3.43) | 0.833 | 5.0 (0.6, 9.4) | 23/333 | 0.68 (0.30, 1.56) | 0.364 | 4.0 (24/599) |
| Headache | 3.4 (2.2, 4.6) | 86/2830 | 2.6 (1.5, 3.7) | 34/1122 | 0.81 (0.53, 1.24) | 0.331 | 2.8 (1.2, 4.4) | 20/554 | 0.94 (0.57, 1.55) | 0.798 | 4.0 (24/599) |
| Injection-site reactions | 2.2 (1.3, 3.1) | 64/2831 | 1.7 (0.9, 2.5) | 26/1184 | 1.06 (0.67, 1.67) | 0.816 | 2.0 (0.4, 3.6) | 13/522 | 1.02 (0.54, 1.93) | 0.955 | 5.4 (72/1335) |
| Gastrointestinal disorders | 5.6 (2.7, 8.4) | 118/1620 | 5.3 (1.9, 8.7) | 33/580 | 1.09 (0.68, 1.75) | 0.73 | 6.8 (0.1, 13.4) | 18/301 | 0.81 (0.47, 1.39) | 0.441 | 6.3 (38/599) |
| Nasopharyngitis | 6.2 (3.6, 8.8) | 115/1746 | 4.2 (2.1, 6.3) | 28/580 | 1.39 (0.93, 2.08) | 0.11 | 4.8 (1.6, 8.0) | 18/333 | 0.54 (0.30, 1.15) | 0.113 | 11.5 (153/1335) |
| Influenza | 1.7 (0.5, 2.8) | 27/1220 | 2.0 (0, 4.3) | 9/317 | 0.89 (0.38, 2.07) | 0.792 | 2.1 (0.1, 4.0) | 5/179 | 0.34 (0.10, 1.18) | 0.090 | 7.3 (97/1335) |
| Upper respiratory tract infection | 4.2 (2.5, 5.9) | 43/1015 | 2.9 (0.3, 5.6) | 12/317 | 1.01 (0.54, 1.90) | 0.964 | 5.3 (0, 14.4) | 5/77 | 0.74 (0.22, 2.50) | 0.624 | 8.5 (113/1335) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; CK, creatine kinase; NA, not applicable; TEAE, treatment emergent adverse event; ULN, upper limit of normal