An Updated Meta-Analysis for Safety Evaluation of Alirocumab and Evolocumab as PCSK9 Inhibitors

Table 1

General characteristics of included studies.

Study	Phase	Participants	Duration, (weeks)	Intervention, N	Control, N	Background LMT	Statin	Risk of bias
Evolocumab
LAPLACE-TIMI 57 (2012) [22]	2	HC	12	70/104/140 mg Q2W, 236; 280/350/420 mg Q4W, 238	Placebo Q2W,78; Placebo Q4W, 77	Statin with or w/o EZE	Both	Low risk
MENDEL (2012) [23]	2	HC	12	70/104/140 mg Q2W, 136; 280/350/420 mg Q4W, 135	Placebo Q2W, 45; Placebo Q4W, 45; EZE, 45	No LMT	None	Low risk
RUTHERFORD (2012) [24]	2	He FH	12	350/420 mg Q4W, 111	Placebo, 56	Stable LMT	Both	Some concerns
GAUSS (2012) [25]	2	HC	12	280/350/420 mg Q4W, 95	Placebo/EZE, 32	Stable LMT	Both	Low risk
DESCARTES (2014) [26]	3	HC	52	420 mg Q4W, 599	Placebo, 302	Stable LMT	Both/none	Some concerns
YUKAWA-1 (2014) [27]	2	HC	12	70/140 mg Q2W, 101; 280/420 mg QM, 104	Placebo Q2W. 52; Placebo QM, 50	Stable statin	Both	Some concerns
MENDEL-2 (2014) [28]	3	HC	12	140 mg Q2W, 153; 420 mg Q4W, 153	Placebo Q2W, 76; Placebo Q4W, 78; EZE, 77	Stable LMT	NA	Some concerns
LAPACE-2 (2014) [29]	3	HC	12	140 mg Q2W or 420 mg Q4W, 1117	Placebo, 558; EZE, 221	Stable statin	Both	Some concerns
GAUSS-2 (2014) [30]	3	HC	12	140 mg Q2W, 103; 420 mg Q4W, 102	EZE, 51	Stable LMT	NA	Some concerns
OSLER (2015) [16]	2/3	HC; He FH	48-56	140 mg Q2W or 420 mg Q4W, 2976	Standard therapy, 1489	NA	NA	Some concerns
TESLA part B (2015) [31]	3	He FH	12	420 mg Q4W, 33	Placebo, 16	Stable LMT	Both	Low risk
RUTHERFORD-2 (2015) [32]	3	He FH	12	140 mg Q2W, 110; 420 mg Q4W, 110	Placebo Q2W, 54; Placebo Q4W, 55	Stable LMT	NA	Low risk
GALGOV (2016) [33]	3		76	420 mg Q4W, 484	Placebo, 484	Stable LMT	Both	Low risk
YUKAWA-2 (2016) [34]	3	HC	12	140 mg Q2W or 420 mg Q4W, 202	Placebo, 202	Stable statin	Both	Some concerns
FOURIER (2017) [4]	3	HC	113	140 mg Q2W or 420 mg Q4W, 13769	Placebo, 13756	NA	Both	Low risk
TAUSSIG (2017) [35]	3	Homozygous FH	48	420 mg Q4W, 106	None	NA	NA	Some concerns
Stiekema et al. [36]	3b	HC	16	420 mg Q4W, 65	Placebo, 64	Stable LMT	Both	Some concerns
GAUSS-4 (2020) [37]	3	HC	12+52	140 mg Q2W, 19; 420 mg Q4W, 21	EZE, 21	Stable statin	Both	Some concerns
BERSON (2019) [38]	3		12	140 mg Q2W or 420 mg Q4W, 657	Placebo, 324	ATO 20 mg	Both	Low risk
BANTING (2019) [39]	3		12	420 mg Q4W, 280	Placebo, 141	NA	NA	Low risk
BEIJERINCK (2020) [40]	3		24	420 mg Q4W, 307	Placebo, 157	Stable LMT	Both	Some concerns
HAUSER-RCT (2020) [41]	3	Pediatric FH	24	420 mg Q4W, 104	Placebo, 53	Stable LMT	Both	Some concerns
Alirocumab
McKenney et al. [42]	2	HC	12	50/100/150 mg Q2W or 200/300 mg Q4W, 151	Placebo, 31	ATO 10/20/40 mg	Both	Low risk
Roth et al. [43]	2	HC	8	150 mg Q2W, 61	Placebo, 31	Stable statin	Both	Low risk
Stein et al. [44]	2	He FH	12	150 mg Q2W or 150/200/300 Q4W, 62	Placebo, 15	Stable statin	Both	Low risk
Roth et al. [45]	3	HC	24	75/150 mg Q2W, 52	EZE, 51	No LMT	None	Low risk
ODYSSEY ALTERNATIVE (2015) [46]	3	Statin-intolerant HC	24	75/150 mg Q2W, 126	EZE, 124	Stable statin	Both	Low risk
ODYSSEY OPTIONS I (2015) [47]	3	HC	24	75/150 mg Q2W, 104	EZE, 101	Stable statin	Both	Low risk
ODYSSEY COMBO I (2015) [48]	3	HC	52	75/150 mg Q2W, 207	Placebo, 107	Stable LMT	Both	Low risk
ODYSSEY FH I & FH II (2015) [49]	3	He FH	78	75/150 mg Q2W, 167	Placebo, 81	Stable LMT	Both	Some concerns
ODYSSEY LONG TERM (2015) [50]	3	HC	78	150 mg Q2W, 1550	Placebo, 788	Stable LMT	Both	Low risk
ODYSSEY MONO (2015) [17]	3	HC	32	75/150 mg Q2W, 52	EZE, 51	No LMT	None	Some concerns
ODYSSEY OPTIONS II (2016) [51]	3	HC	2	75/150 mg Q2W, 103	EZE, 101	Rosuvastatin	Both	Low risk
ODYSSEY ESCAPE (2016) [52]	3	HC	18	150 mg Q2W, 41	Placebo, 21	NA	NA	Some concerns
ODYSSEY CHOICE I (2016) [53]	3	HC	48	75/150 mg Q2W,	Placebo/EZE	Stable LMT	Both/none	Low risk
ODYSSEY CHOICE II (2016) [54]	3	HC	24	75/150 mg Q2W or 300 mg Q4W, 573	Placebo, 229	Fenofibrate, EZE or diet	None	Some concerns
ODYSSEY JAPAN (2016) [55]	3	He FH	52	75/150 mg Q2W, 143	Placebo, 72	Stable LMT	Both	Low risk
Teramoto et al. [56]	2	HC	12	75/150 mg Q2W, 107	Placebo, 56	Stable LMT	Both	Some concerns
ODYSSEY COMBO II (2017) [57]	3		104	75/150 mg Q2W, 411	EZE, 209	Stable LMT	Both/none	Low risk
ODYSSEY HIGH FH (2016) [58]	3	He FH	78	150 mg Q2W, 72	Placebo, 35	Stable LMT	Both	Some concerns
ODYSSEY DM INSULIN (2017) [59]	3		24	75/150 mg Q2W, 344	Placebo, 170	Stable LMT	Both	Some concerns
ODYSSEY KT (2018) [60]	3	HC	24	75/150 mg Q2W, 97	Placebo, 102	Stable LMT	Both	Some concerns
ODYSSEY DM-DYSLIPIDEMIA (2018) [61]	3b/4		24	75/150 mg Q2W, 275	Usual care, 137	Maximally tolerated dose of stain	Both	Some concerns
ODYSSEY OUTCOMES (2018) [3]	3		257	75/150 mg Q2W, 9451	Placebo, 9443	Stable LMT	Both	Low risk
ODYSSEY J-IVUS (2019) [62]	4		36	75/150 mg Q2W, 103	Standard therapy,	Stable LMT	Both	Some concerns
ODYSSEY NIPPON (2019) [63]	3	He FH; Non FH	64	150 mg Q2W, 158	None	ATO 5 mg or nonstatin	Both	Some concerns
ODYSSEY HoFH (2020) [64]	3	Homozygous FH	24	150 mg Q2W, 45	Placebo, 24	Statin with or w/o EZE	Both	Some concerns
ODYSSEY EAST(2020) [65]	3	HC	24	75/150 mg Q2W, 406	EZE, 206	Maximally tolerated dose of stain	Both	Some concerns
Janik et al. [66]	4	He FH; Non FH	96	75/150 mg Q2W, 1087	Placebo, 1084	Stable LMT	Both	Some concerns

Abbreviations: ATO: atorvastatin; ACS: acute coronary syndrome; ASCVD: atherosclerotic cardiovascular disease; CAD: coronary artery disease; DM: diabetes mellitus; EZE: ezetimibe; He FH: heterozygous familial hyperlipidemia; LMT: lipid modifying therapy; NA: not reported.