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. 2021 Mar 19;28(5):417–434. doi: 10.5551/jat.56762

Table 6. A summary of clinical trials and meta-analyses of PCSK9 inhibitors 83 - 87) .

PCSK9 Inhibitor Study design and subjects Summary of findings References
Alirocumab

  • • A meta-analysis of 25 RCTs encompassing 12,200 patients with both familial and non-familial hypercholesterolemia

  • • Biweekly 50 to 150 mg alirocumab:

→ Reduced LDL cholesterol by -52.6% (95% CI: -58.2 to -47.0%) versus placebo and by -29.9% (95% CI: -32.9 to -26.9%) versus ezetimibe

→ Increased high-density lipoprotein (HDL) cholesterol by 8.0% (95% CI: 4.2 to 11.7%) versus placebo

 83)
Alirocumab

  • • ODYSSEY Open-Label Extension (OLE) study

  • • 167 patients with HeFH who had completed an earlier double-blind, RCT parent study

  • • Patients were initiated on 75 mg biweekly alirocumab unless baseline LDL-C was ＞ 8.9 mmol/l, in which case they received biweekly 150 mg alirocumab

  • • Biweekly 75 to 150 mg alirocumab:

→ At week 144, the mean LDL cholesterol level was reduced by 48.7% compared to the mean level at baseline (3.65±1.9 mmol/L [standard deviation, SD])

→ Injection site reactions reported for eight patients, with one treatment discontinuation

→ Treatment emergent anti-drug antibodies were identified in five patients but did not affect efficacy

 84)
Alirocumab

  • • ODYSSEY OUTCOMES study

  • • 18,924 patients:

→ Who had an ACS within the previous 12 months

→ With LDL cholesterol ≥ 70 mg/dL (1.8 mmol/L), non-HDL cholesterol level ≥ 100 mg/dL (2.6 mmol/L), or an apolipoprotein B level ≥ 80 mg/dL

→ Receiving high-intensity dose or maximum tolerated dose of statin

  • • Biweekly 50 to 150 mg alirocumab:

→ Significantly reduced the risk of the primary efficacy end point a (903 patients [9.5%] vs. 1052

patients [11.1%]; HR, 0.85; 95% CI 0.78 to 0.93; p ＜0.001)

→ Significantly reduced the risk of the major secondary efficacy end point b (1199 patients [12.7%] vs. 1349 patients [14.3%]; HR, 0.88; 95% CI 0.81-0.95; p = 0.001)

85)
Evolocumab

  • • A meta-analysis of 25 RCTs encompassing 12,200 patients with both familial and non-familial hypercholesterolemia

  • • Monthly 420 mg evolocumab:

→ Reduced LDL cholesterol by -54.6% (95% CI: -58.7 to -50.5%) versus placebo and by -36.3% (95% CI: -38.8 to -33.9%) versus ezetimibe

→ Increased HDL cholesterol by 7.6% (95% CI: 5.7 to 9.5%) versus placebo

 83)
Evolocumab

  • • TAUSSIG open-label study final report

  • • 300 patients with HoFH ( n = 106) and severe HeFH ( n = 194)

  • • Patients undergoing apheresis at enrollment received biweekly 420 mg evolocumab immediately after apheresis

  • • Patients not undergoing apheresis at baseline received monthly 420 mg evolocumab

  • • Dose regimen could be changed at the clinician’s discretion

  • • Biweekly or Monthly 420 mg evolocumab:

→ In HoFH patients, mean percentage changes (±SD) in LDL cholesterol relative to baseline were -21.2±25.0% at week 12 and -24.0±41.3% at week 216

→ In HeFH, mean percentage changes (±SD) in LDL cholesterol relative to baseline were -54.9± 17.4% at week 12 and -47.2±27.9% at week 216

→ Potential injection site reactions were reported for 14 and 22 patients with HoFH and HeFH, respectively

→ No neutralizing antievolocumab antibodies were detected

 86)
Evolocumab

  • • FOURIER OUTCOMES study

  • • 27,564 patients:

→ Had clinically evident ASCVD

→ With LDL cholesterol ≥ 70 mg/dL (1.8 mmol/L), non-HDL cholesterol level ≥ 100 mg/dL (2.6 mmol/L)

→ Taking an optimized regimen of lipid-lowering therapy

  • • Biweekly 140 mg or Monthly 420 mg evolocumab:

→ Significantly reduced the risk of the primary efficacy end point c (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio [HR], 0.85; 95% CI: 0.79 to 0.92; p ＜0.001)

→ Significantly reduced the risk of key secondary efficacy end point d (816 patients [5.9%] vs. 1013 patients [7.4%]; HR, 0.80; 95% CI, 0.73 to 0.88; p ＜0.001)

87)

a. The composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalisation

b. Any coronary heart disease event defined as death from coronary heart disease, nonfatal myocardial infarction, unstable angina requiring hospitalisation, and an ischemia-driven coronary revascularization procedure

c. The composite of cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina, or coronary revascularization

d. The composite of cardiovascular death, myocardial infarction, or stroke