PCSK9 inhibitor trials
| Triala | PCSK9 inhibitor | Definition of statin intolerance | Statin rechallenge | LDL-C reduction with PCSK9 inhibitor | LDL-C reduction with ezetimibea | Patients with muscle events during trial |
|---|---|---|---|---|---|---|
| GAUSS-2, 201432 | Evolocumab | Intolerable muscle-related side effects to ≥ 2 statins; most participants unable to tolerate ≥ 3 statins | No | 56.1% (140 mg every 2 weeks) 55.3% (420 mg per month) | 19.2% | 12% (evolocumab) 23% (ezetimibe) |
| GAUSS-3, 201618 | Evolocumab | Intolerance to atorvastatin 10 mg and another statin at any dose; or 3 or more statins, with 1 at the lowest daily dose and 2 others at any dose | Yes | 52.8% (420 mg per month) | 16.7% | 20.7% (evolocumab) 28.8% (ezetimibe) HR 0.68; 95% CI 0.39-1.19 |
| ODYSSEY ALTERNATIVE, 201519 | Alirocumab | Inability to tolerate 2 or more statins because of unexplained skeletal muscle-related symptoms with one of the 2 statins at the lowest-approved daily starting dose. | Yes | 45.0% (75 mg every 2 weeks) | 14.6% | 32.5% (alirocumab) 41.1% (ezetimibe) HR 0.71; 95% CI 0.47 to 1.06 |
↵a All trials used ezetimibe 10 mg daily as the nonstatin comparator.
CI = confidence interval; HR = hazard ratio; LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9