Risks of muscle toxicity by various case definitions
| Outcome definitions | Number of cases with events | Number of eligible persons | Person-years | Incidence * (95% CI) |
|---|---|---|---|---|
| Base-case definition: criterion A (diagnosis of ‘myositis’ or ‘rhabdomyolysis’) or criterion B (CK >10×ULN) | 43 | 18036 | 42193 | 1.02 (0.76 to 1.37) |
| With discontinuation | 10 | 0.24 (0.13 to 0.44) | ||
| With switching | 3 | 0.07 (0.02 to 0.22) | ||
| With renal dysfunction | 17 | 0.40 (0.25 to 0.65) | ||
| With hospitalisation | 17 | 0.40 (0.25 to 0.65) | ||
| Criterion A or CK >5×ULN | 87 | 18036 | 42193 | 2.06 (1.67 to 2.54) |
| With discontinuation | 23 | 0.55 (0.36 to 0.82) | ||
| With switching | 7 | 0.17 (0.08 to 0.35) | ||
| With renal dysfunction | 39 | 0.92 (0.68 to 1.27) | ||
| With hospitalisation | 34 | 0.81 (0.58 to 1.13) | ||
| Criteria A and B | 4 | 18036 | 42193 | 0.09 (0.04 to 0.25) |
| With discontinuation | 3 | 0.07 (0.02 to 0.22) | ||
| With switching | 1 | 0.02 (0.00 to 0.17) | ||
| With renal dysfunction | 3 | 0.07 (0.02 to 0.22) | ||
| With hospitalisation | 4 | 0.09 (0.04 to 0.25) | ||
| Myositis (and criterion B) | 0 | – | ||
| Rhabdomyolysis (and criterion B) | 4 | 0.09 (0.04 to 0.25) | ||
| Criterion A and CK >5×ULN | 8 | 18036 | 42193 | 0.19 (0.09 to 0.38) |
| With discontinuation | 3 | 0.07 (0.02 to 0.22) | ||
| With switching | 1 | 0.02 (0.00 to 0.17) | ||
| With renal dysfunction | 6 | 0.14 (0.06 to 0.32) | ||
| With hospitalisation | 7 | 0.17 (0.08 to 0.35) | ||
| Myositis (and CK >5×ULN) | 0 | – | ||
| Rhabdomyolysis (and CK >5×ULN) | 8 | 0.19 (0.09 to 0.38) | ||
| Criterion A | 27 | 18036 | 42193 | 0.64 (0.44 to 0.93) |
| With discontinuation | 7 | 0.17 (0.08 to 0.35) | ||
| With switching | 3 | 0.07 (0.02 to 0.22) | ||
| With renal dysfunction | 9 | 0.21 (0.11 to 0.41) | ||
| With hospitalisation | 8 | 0.19 (0.09 to 0.38) | ||
| Myositis | 12 | 0.28 (0.16 to 0.50) | ||
| Rhabdomyolysis | 15 | 0.36 (0.21 to 0.59) | ||
| Criterion B | 20 | 18036 | 42193 | 0.47 (0.31 to 0.73) |
| With discontinuation | 6 | 0.14 (0.06 to 0.22) | ||
| With switching | 1 | 0.02 (0.00 to 0.17) | ||
| With renal dysfunction | 11 | 0.26 (0.14 to 0.47) | ||
| With hospitalisation | 13 | 0.31 (0.18 to 0.53) | ||
| CK >5×ULN | 68 | 1.61 (1.27 to 2.04) | ||
| Baseline period | ||||
| Base-case definition: 3 months | 43 | 18036 | 42193 | 1.02 (0.76 to 1.37) |
| 6 months | 40 | 16649 | 38645 | 1.04 (0.76 to 1.41) |
| 12 months | 31 | 13693 | 29387 | 1.05 (0.74 to 1.50) |
| Statin exposure status | ||||
| Base-case definition: continuous exposure | 43 | 18036 | 42193 | 1.02 (0.76 to 1.37) |
| Excluding stopping periods (days of statin supply) | 39 | 18036 | 38027 | 1.03 (0.75 to 1.40) |
*Data shown as per 1000 person-years with 95% CI.
Discontinuation was defined as no use of statin therapy in the 6 months following occurrence of muscle toxicity. Switching was defined as patients who initiated another statin in the following period. Renal dysfunction was defined as serum creatine increased above the upper limit of normal range within 3 days before or 7 days after occurrence of an event.
CK, creatine kinase; ULN, upper limit of the normal range.