PCSK9 Inhibitors

Description Results NMA

myocardial infarction as adverse event 0.39 [0.20; 0.79]

death from all causes as adverse event 0.29 [0.09; 0.99]

General allergic reaction 1.06 [0.81; 1.37]

serious adverse events 0.96 [0.80; 1.14]

cardiovascular events as adverse events 0.91 [0.63; 1.33]

Neurocognitive disorder 2.28 [0.78; 6.72]

neurological SAE 0.94 [0.63; 1.41]

cardiovascular death as adverse event 0.41 [0.16; 1.02]

serious adverse events 1.19 [0.53; 2.65]

death from all causes as adverse event NaN [NaN; NaN]

myocardial infarction as adverse event ∞ [NaN; ∞]

cardiovascular death as adverse event NaN [NaN; NaN]

CHD events 0.85 [0.78; 0.93] Demonstrated

major CHD event 0.88 [0.80; 0.96] Demonstrated

cardiovascular events 0.87 [0.81; 0.94] Demonstrated

all causes deaths 0.85 [0.73; 0.98]

cardiovascular death 0.88 [0.74; 1.05]

CHD death 0.92 [0.76; 1.11]

cardiovascular death 0.88 [0.74; 1.05]

serious adverse events 0.98 [0.06; 15.26]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular death as adverse event NaN [NaN; NaN]

serious adverse events 0.97 [0.31; 3.01]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular death as adverse event NaN [NaN; NaN]

serious adverse events 0.56 [0.17; 1.86]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular death as adverse event 0.00 [0.00; NaN]

serious adverse events 0.74 [0.26; 2.04]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular death as adverse event 0.00 [0.00; NaN]

serious adverse events 0.95 [0.52; 1.74]

death from all causes as adverse event 0.51 [0.03; 8.11]

myocardial infarction as adverse event 0.51 [0.03; 8.11]

cardiovascular death as adverse event 0.34 [0.06; 2.01]

serious adverse events 1.05 [0.76; 1.46]

death from all causes as adverse event 0.50 [0.07; 3.55]

cardiovascular death as adverse event 0.25 [0.05; 1.36]

alirocumab 150 mg as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. (n=1553)

vs.

placebo (n=788)

Sample size: 1553/788

Primary endpoint: change in LDL at week 24

FU duration: 78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: percent change in LDL-C from baseline to week 24

FU duration: 24 wk

Alirocumab (on top intensive or maximum-tolerated statin therapy) (n=9462)

vs.

placebo (n=9462)

double-blind

Parallel groups

Sample size: 9462/9462

Primary endpoint:

FU duration: 2.8 yr (median)

Alirocumab 75 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double blind

Sample size: -9/-9

Primary endpoint:

FU duration: 78 wk

Alirocumab 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 52–78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 52 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 104 wk

serious adverse events 1.28 [0.68; 2.40]

death from all causes as adverse event ∞ [NaN; ∞]

cardiovascular events as adverse events 1.51 [0.31; 7.45]

serious adverse events ∞ [NaN; ∞]

death from all causes as adverse event NaN [NaN; NaN]

Muscle-related adverse events 0.81 [0.31; 2.12]

serious adverse events ∞ [NaN; ∞]

death from all causes as adverse event NaN [NaN; NaN]

serious adverse events 0.88 [0.45; 1.73]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular events as adverse events 1.25 [0.24; 6.42]

Neurocognitive disorder ∞ [NaN; ∞]

Muscle-related adverse events 1.85 [1.11; 3.09]

serious adverse events 3.01 [0.87; 10.45]

death from all causes as adverse event NaN [NaN; NaN]

serious adverse events 0.69 [0.23; 2.14]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular events as adverse events ∞ [NaN; ∞]

Muscle-related adverse events 4.95 [0.64; 38.21]

Neurocognitive disorder NaN [NaN; NaN]

cardiovascular events 0.80 [0.73; 0.88] Demonstrated

stroke (fatal and non fatal) 0.79 [0.66; 0.95]

MI ( (fatal and non fatal) 0.73 [0.65; 0.82]

cardiovascular death 1.05 [0.88; 1.25]

all causes deaths 1.04 [0.91; 1.19]

cardiovascular death 1.05 [0.88; 1.25]

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

evolocumab (420 mg) every 4 weeks (n=599)

vs.

placebo (n=302)

Sample size: 599/302

Primary endpoint:

FU duration: 52 weeks

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, (n=-9)

vs.

placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=95)

vs.

(n=32)

placebo- and ezetimibe-controlled

Sample size: 95/32

Primary endpoint:

FU duration:

AMG 145 350 mg, AMG 145 420 mg (n=111)

vs.

placebo (n=56)

Sample size: 111/56

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

evolucumab + statin (n=1117)

vs.

placebo + statin (n=558)

Sample size: 1117/558

Primary endpoint:

FU duration:

evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) (n=102)

vs.

ezetimibe 10 mg (n=205)

Sample size: 102/205

Primary endpoint:

FU duration:

subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly (n=220)

vs.

placebo (n=109)

Sample size: 220/109

Primary endpoint:

FU duration:

evolocumab (either 140 mg every 2 weeks or 420 mg monthly) (n=-9)

vs.

placebo (n=-9)

3 arms

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 2.2 years