Table 3.
Fractions of Drug Trials That Resulted in Muscle-Related Adverse Effects Correlated with Drug Potency
| Drug | No. of Trials Involving the Drug | No. (%) of Trials That Resulted in Muscle-Related Adverse Effectsa, b | Rank Order Potencyc, d |
|---|---|---|---|
| Current statins | |||
| Atorvastatin | 255 | 240 (94) | 1, 2e |
| Rosuvastatin | 40 | 32 (80) | 1, 2e |
| Simvastatin | 148 | 114 (77) | 3 |
| Pravastatin | 78 | 52 (67) | 4 |
| Lovastatin | 62 | 38 (61) | 4 |
| Fluvastatin | 11 | 9 (82)f | 5 |
| Other lipid-lowering agents | |||
| Cerivastating | 23 | 17 (74)f | — |
| Ezetimibe | 29 | 13 (45)f | — |
| Simvastatin-ezetimibe | 16 | 15 (94)f | — |
| Niacin | 14 | 3 (21)f | — |
| Gemfibrozil | 10 | 5 (50)f | — |
| Fenofibrate | 4 | 4 (100)f | — |
If the patient switched to a new drug without time off between drugs, the second drug is reported here as a new trial if the patient reported a change in severity of the muscle-related symptoms. Only the drug that was used during the onset of muscle-related symptoms is reported here if subsequent drugs used did not result in a change of symptoms because it is not possible to determine if persistent symptoms reflected lack of resolution (index drug) versus reproduction of symptoms (new drug[s]).
The percentages represent trials by those who experienced muscle-related symptoms and are not indicative of trials of general statin users.
The p values for potency are as follows: atorvastatin vs lovastatin, p<0.0000001; atorvastatin vs lovastatin + pravastatin, p<0.0000001; atorvastatin + rosuvastatin vs lovastatin + pravastatin, p<0.0000001; atorvastatin vs simvastatin, p<0.0000002; atorvastatin + rosuvastatin vs simvastatin, p=0.000003; simvastatin vs lovastatin + pravastatin, p=0.01.
The test of trend p values are as follows: atorvastatin + rosuvastatin vs simvastatin vs lovastatin + pravastatin p<0.0000001; atorvastatin vs rosuvastatin + simvastatin vs lovastatin + pravastatin p<0.0000001; atorvastatin vs simvastatin vs lovastatin + pravastatin p<0.0000001.
Although rosuvastatin is more potent than atorvastatin per milligram, it is not as commonly prescribed or used at high doses. Whereas an 80-mg dose of atorvastatin is commonly used and widely advocated, a 40-mg dose of rosuvastatin has been discouraged by the U.S. Food and Drug Administration.28
These percentages are based on a small number of trials.
Cerivastatin was withdrawn from the U.S. market.