Table 4. Major clinical trials of PSCK9 inhibitors.
| Characteristics | GLAGOV (2016)42 | FOURIER (2017)8 | ODYSSEY LONG TERM (2015)9 | ODYSSEY OUTCOMES (2018)7 |
|---|---|---|---|---|
| Study type | Phase III | Phase III | Phase III | Phase III |
| Drug | Evolocumab | Evolocumab | Alirocumab | Alirocumab |
| Intervention | Statin + evolocumab vs. statin + placebo | Statin + evolocumab vs. statin + placebo | Statin + alirocumab vs. statin + placebo | Statin + alirocumab vs. statin + placebo |
| Study population | - 968 patients with coronary atherosclerosis | 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol ≥70 mg/dL | 2,341 patients at high risk for cardiovascular events who had LDL cholesterol ≥70 mg/dL with maximum tolerated dose of statins | 18,924 patients with ACS 1 to 12 months earlier and LDL cholesterol ≥70 mg/dL, non-HDL cholesterol ≥100 mg/dL, apolipoprotein B ≥80 mg/dL with high intensity/maximum tolerated dose of statins |
| - At least 4 weeks of statin therapy with LDL cholesterol ≥80 mg/dL or 60 mg/dL ≤ LDL cholesterol ≤80 mg/dL with 1 major or 3 minor CV risk factors | ||||
| Median duration of follow-up | 76 wk | 2.2 yr | 80.9 wk | 2.8 yr |
| Primary efficacy endpoint | Nominal change in PAV from baseline to week 78, measured by serial IVUS imaging | Composite of MACE: cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization | Percentage change in calculated LDL cholesterol level from baseline to week 24 | Composite of MACE: coronary heart disease death, MI, ischemic stroke, and unstable angina requiring hospitalization |
| Results | PAV: | - LDL cholesterol: 59% reduction compared to placebo | LDL change at week 24, the difference between the alirocumab and placebo groups −62% (p<0.001); the treatment effect remained consistent over a period of 78 weeks | Composite of MACE: 9.5% in alirocumab group vs. 11.1% in placebo (HR, 0.85; p<0.001) |
| - Increased by 0.05% in placebo group | - Major cardiovascular events: ARR by 1.5% | |||
| - Decreased by 0.95% in evolocumab group |
PSCK9, proprotein convertase subtilisin/kexin type 9; GLAGOV, GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound; FOURIER, Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk; LDL, low-density lipoprotein; CV, cardiovascular; ACS, acute coronary syndrome; HDL, high-density lipoprotein; PAV, percent atheroma volume; IVUS, intravascular ultrasonography; MACE, major adverse cardiovascular events; MI, myocardial infarction; ARR, absolute risk reduction; HR, hazard ratio.