Clinical trials of PCSK9 Inhibitors - TrialResults-center.org

pathology

treatment

patient

Demonstrated benefit and harm

cardiovascular prevention

alirocumab

not classified

versus

alirocumab superior to placebo (on top statins) in terms of CHD events in ODYSSEY OUTCOMES, 2018

alirocumab superior to placebo (on top statins) in terms of major CHD event in ODYSSEY OUTCOMES, 2018

alirocumab superior to placebo (on top statins) in terms of cardiovascular events in ODYSSEY OUTCOMES, 2018

alirocumab inferior to placebo (on top statins) in terms of death from all causes as adverse event in ODYSSEY Long-Term, 2015

meta-analysis

Trial	control	p<0.05	harm	NS
ODYSSEY Long-Term, 2015	alirocumab vs placebo (on top statins)	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]
ODYSSEY Alternative	alirocumab vs placebo (on top statins)			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]
ODYSSEY OUTCOMES, 2018	alirocumab vs placebo (on top statins)	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]
ODYSSEY MONO	alirocumab vs ezetimibe alone			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]
ODYSSEY FH 1	alirocumab vs placebo (on top statins)
ODYSSEY FH 2	alirocumab vs placebo (on top statins)
ODYSSEY HIGH FH	alirocumab vs placebo (on top statins)			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]
ODYSSEY OPTIONS I	alirocumab vs ezetimibe (on top statin)			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]
ODYSSEY OPTIONS II	alirocumab vs ezetimibe (on top statin)			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]
ODYSSEY COMBO	alirocumab vs placebo (on top statins)			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]
ODYSSEY COMBO II	alirocumab vs placebo (on top statins)			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]

Trial	Treatments	Patients	Method
ODYSSEY Long-Term, 2015	alirocumab 150 mg as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. (n=1553) vs. placebo (n=788)	patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy	Sample size: 1553/788 Primary endpoint: change in LDL at week 24 FU duration: 78 wk
ODYSSEY Alternative	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Ezetimibe 10 mg (n=-9)	statin-intolerant patients	double-blind Sample size: -9/-9 Primary endpoint: percent change in LDL-C from baseline to week 24 FU duration: 24 wk
ODYSSEY OUTCOMES, 2018	Alirocumab (on top intensive or maximum-tolerated statin therapy) (n=9462) vs. placebo (n=9462)	Post-ACS patients (1 to 12 months)with elevated levels of atherogenic lipoproteins despite intensive or maximum-tolerated statin therapy	double-blind Parallel groups Sample size: 9462/9462 Primary endpoint: FU duration: 2.8 yr (median)
ODYSSEY MONO	Alirocumab 75 mg Q2W (n=-9) vs. Ezetimibe 10 mg (n=-9)	hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy	double-blind Sample size: -9/-9 Primary endpoint: FU duration: 24 wk
ODYSSEY FH 1	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Placebo (n=-9)	patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy	double-blind Sample size: -9/-9 Primary endpoint: FU duration: 78 wk
ODYSSEY FH 2	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Placebo (n=-9)	patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy	double blind Sample size: -9/-9 Primary endpoint: FU duration: 78 wk
ODYSSEY HIGH FH	Alirocumab 150 mg Q2W (n=-9) vs. Placebo (n=-9)	patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy	Sample size: -9/-9 Primary endpoint: FU duration: 52–78 wk
ODYSSEY OPTIONS I	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Ezetimibe 10 mg (n=-9)	high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg)	Sample size: -9/-9 Primary endpoint: FU duration: 24 wk
ODYSSEY OPTIONS II	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Ezetimibe 10 mg (n=-9)	high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg)	Sample size: -9/-9 Primary endpoint: FU duration: 24 wk
ODYSSEY COMBO	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Placebo (n=-9)	high cardiovascular risk patients on maximally tolerated statin therapy	double-blind Sample size: -9/-9 Primary endpoint: FU duration: 52 wk
ODYSSEY COMBO II	Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9) vs. Ezetimibe 10 mg (n=-9)	high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins	double-blind Sample size: -9/-9 Primary endpoint: FU duration: 104 wk

cardiovascular prevention

evolocumab

not classified

versus

evolocumab superior to placebo (on top statins) in terms of cardiovascular events in FOURIER, 2017

evolocumab inferior to ezetimibe alone in terms of Muscle-related adverse events in GAUSS 2

meta-analysis

Trial	control	p<0.05	harm	NS
MENDEl 2	evolocumab vs
DESCARTES, 2014	evolocumab vs placebo (on top statins)			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]
Mendel 1, 2012	evolocumab vs
LAPLACE-TIMI 57	evolocumab vs placebo (on top statins)
GAUSS 1, 2012	evolocumab vs placebo			serious adverse events ∞ [NaN; ∞] death from all causes as adverse event NaN [NaN; NaN] Muscle-related adverse events 0.81 [0.31; 2.12]
RUTHERFORD-1	evolocumab vs placebo (on top statins)			serious adverse events ∞ [NaN; ∞] death from all causes as adverse event NaN [NaN; NaN]
YUKAWA-1, 2014	evolocumab vs
LAPLACE 2, 2014	evolocumab vs placebo (on top statins)			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; ∞]
GAUSS 2	evolocumab vs ezetimibe alone		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]
RUTHERFORD-2, 2015	evolocumab vs placebo (on top statins)			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]
FOURIER, 2017	evolocumab vs placebo (on top statins)	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]

Trial	Treatments	Patients	Method
MENDEl 2	(n=-9) vs. (n=-9)		Sample size: -9/-9 Primary endpoint: FU duration:
DESCARTES, 2014	evolocumab (420 mg) every 4 weeks (n=599) vs. placebo (n=302)		Sample size: 599/302 Primary endpoint: FU duration: 52 weeks
Mendel 1, 2012	(n=-9) vs. (n=-9)		Sample size: -9/-9 Primary endpoint: FU duration:
LAPLACE-TIMI 57	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:
GAUSS 1, 2012	(n=95) vs. (n=32) placebo- and ezetimibe-controlled	statin-intolerant patients	Sample size: 95/32 Primary endpoint: FU duration:
RUTHERFORD-1	AMG 145 350 mg, AMG 145 420 mg (n=111) vs. placebo (n=56)	heterozygous familial hypercholesterolemia patients	Sample size: 111/56 Primary endpoint: FU duration:
YUKAWA-1, 2014	(n=-9) vs. (n=-9)		Sample size: -9/-9 Primary endpoint: FU duration:
LAPLACE 2, 2014	evolucumab + statin (n=1117) vs. placebo + statin (n=558)		Sample size: 1117/558 Primary endpoint: FU duration:
GAUSS 2	evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) (n=102) vs. ezetimibe 10 mg (n=205)	patients with statin intolerance	Sample size: 102/205 Primary endpoint: FU duration:
RUTHERFORD-2, 2015	subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly (n=220) vs. placebo (n=109)	heterozygous familial hypercholesterolaemia	Sample size: 220/109 Primary endpoint: FU duration:
FOURIER, 2017	evolocumab (either 140 mg every 2 weeks or 420 mg monthly) (n=-9) vs. placebo (n=-9) 3 arms	patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy	double-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 2.2 years

PCSK9 Inhibitors Description Results NMA

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