TABLE 1.
Characteristics of included studies.
| No | Year | Author | Trial | Duration, week(s) | Study population | Add-on therapy | Dosage of PCSK9 inhibitor (mg) | Sample size | Age, mean (SD) | Women, % | HP, % | DM, % | LDL-C, mean (SD) | ApoB, mean (SD) | Lp(a), median (SD) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alirocumab | |||||||||||||||
| 1 | 2015 | Bays H | ODYSSEY OPTIONS I | 12/24 | LDL-C ≥ 70 mg/dl with CVD or LDL-C ≥ 100 mg/dl with CVD risk factors | Alirocumab | 75 | 57 | 62.2 (10.0) | 42.1 | 77.2 | 57.9 | 103.9 (34.9) | 90.0 (21.9) | 24.0 (52.6) |
| Ezetimibe | 0 | 55 | 65.7 (9.0) | 43.6 | 81.8 | 52.7 | 100.4 (29.5) | 89.2 (22.6) | 21.0 (27.4) | ||||||
| Alirocumab | 75 | 47 | 64.2 (10.4) | 34 | 76.6 | 53.2 | 116.4 (37.4) | 97.0 (25.5) | 21.0 (44.4) | ||||||
| Ezetimibe | 0 | 47 | 63.9 (10.3) | 23.4 | 78.7 | 34 | 98.9 (29.2) | 83.3 (17.0) | 32.0 (36.3) | ||||||
| 2 | 2015/2017 | Cannon CP/El Shahawy M | ODYSSEY COMBO II | 24/52 | LDL-C ≥ 70 mg/dl with CVD or LDL-C ≥ 100 mg/dl without CVD | Alirocumab | 75 | 479 | 61.7 (9.4) | 24.8 | — | 30.3 | 108.1 (34.7) | 90.0 (20.0) | 28.0 (44.8) |
| Ezetimibe | 0 | 241 | 61.3 (9.2) | 29.5 | — | 31.5 | 104.2 (34.7) | 90.0 (20.0) | 22.4 (36.4) | ||||||
| 3 | 2015 | Kastelein JJP | ODYSSEY FH I, ODYSSEY FH II | 24 | LDL-C ≥ 70 mg/dl and TG ≤ 400 mg/dl with HeFH | Alirocumab | 75 | 323 | 52.1 (12.9) | 44.3 | 43 | 9.9 | 144.7 (52.1) | 114.6 (30.7) | 51.5 (2.8) |
| Placebo | 0 | 163 | 51.7 (12.3) | 42.3 | 43.6 | 15.3 | 144.4 (37.0) | 113.7 (28.4) | 46.9 (4.0) | ||||||
| Alirocumab | 75 | 167 | 53.2 (12.9) | 48.5 | 34.1 | 4.2 | 134.6 (37.5) | 108.0 (27.7) | 49.9 (5.4) | ||||||
| Placebo | 0 | 82 | 53.2 (12.5) | 45.1 | 29.3 | 3.7 | 134.0 (26.3) | 107.7 (23.9) | 50.9 (6.6) | ||||||
| 4 | 2015 | Kereiakes DJ | ODYSSEY COMBO I | 24 | LDL-C ≥ 70 mg/dl with CVD or LDL-C ≥ 100 mg/dl with CHD risk | Alirocumab | 75 | 209 | 63.0 (9.5) | 37.3 | — | 45 | 100.2 (29.5) | 90.8 (21.4) | 31.0 (54.1) |
| Placebo | 0 | 107 | 63.0 (8.8) | 28 | — | 39.3 | 106.0 (35.3) | 91.4 (24.1) | 38.0 (44.4) | ||||||
| 5 | 2015 | Robinson JG | ODYSSEY LONG TERM | 24 | LDL-C ≥ 70 mg/dl with HeFH or CHD | Alirocumab | 150 | 1,530 | 60.4 (10.4) | 36.7 | — | 34.9 | 122.7 (42.6) | 101.9 (27.7) | 22.2 (43.6) |
| Placebo | 0 | 780 | 60.6 (10.4) | 39.8 | — | 33.9 | 121.9 (41.4) | 101.1 (27.3) | 20.9 (44.7) | ||||||
| 6 | 2016 | Farnier M | ODYSSEY OPTIONS II | 12/24 | LDL-C ≥ 70 mg/dl with CVD or LDL-C ≥ 100 mg/dl with CVD risk factors | Alirocumab | 75 | 49 | 62.2 (11.1) | 36.7 | 73.5 | 38.8 | 106.0 (29.1) | 93.4 (22.6) | 22.0 (48.9) |
| Ezetimibe | 0 | 48 | 60.4 (10.4) | 45.8 | 68.8 | 47.9 | 94.7 (33.6) | 89.0 (25.9) | 38.5 (68.1) | ||||||
| Alirocumab | 75 | 54 | 57.9 (8.9) | 48.1 | 74.1 | 33.3 | 114.1 (30.0) | 92.7 (25.2) | 49.5 (65.9) | ||||||
| Ezetimibe | 0 | 53 | 63.1 (10.2) | 41.5 | 67.9 | 39.6 | 115.2 (48.4) | 97.8 (20.4) | 35.5 (45.2) | ||||||
| 7 | 2016 | Ginsberg HN | ODYSSEY HIGH FH | 24 | LDL-C ≥ 160 mg/dl with HeFH | Alirocumab | 150 | 72 | 49.8 (14.2) | 51.4 | 55.6 | 12.5 | 196.3 (57.9) | 138.2 (32.0) | 22.0 (31.1) |
| Placebo | 0 | 35 | 52.1 (11.2) | 37.1 | 60 | 17.1 | 201.0 (43.4) | 146.6 (28.3) | 30.0 (23.0) | ||||||
| 8 | 2016 | Roth EM | ODYSSEY CHOICE I | 24 | LDL-C ≥70 mg/dl with moderate-to-very-high CVD risk or LDL-C ≥ 100 mg/d with moderate CVD risk | Alirocumab | 75 | 78 | 60.7 (9.1) | 34.6 | — | 28.2 | 118.0 (35.1) | 99.6 (25.0) | 28.0 (35.9) |
| Alirocumab | 300 | 312 | 61.6 (10.0) | 39.1 | — | 30.8 | 115.4 (30.6) | 96.6 (21.3) | 27.0 (43.0) | ||||||
| Placebo | 0 | 157 | 61.6 (9.7) | 35.7 | — | 31.8 | 115.8 (37.2) | 96.0 (24.3) | 25.5 (48.9) | ||||||
| 9 | 2016 | Teramoto T | ODYSSEY JAPAN | 24 | LDL-C ≥100 mg/dl with HeFH or Non-FH with high CAD risk or LDL-C ≥ 120 mg/dl | Alirocumab | 75 | 144 | 60.3 (9.7) | 41.7 | — | 72.9 | 142.9 (27.0) | 110.0 (20.0) | 16.8 (19.1) |
| Placebo | 0 | 72 | 61.8 (9.0) | 34.7 | — | 59.7 | 142.9 (27.0) | 110.0 (20.0) | 14.7 (18.7) | ||||||
| 10 | 2017 | Leiter LA | ODYSSEY DM-INSULIN | 24 | LDL-C levels ≥70 mg/dl | Alirocumab | 75 | 294 | 63.9 (8.9) | 45.2 | — | 100 | 112.1 (34.3) | 97.0 (24.7) | 16.0 (37.0) |
| Placebo | 0 | 147 | 64.0 (9.4) | 46.9 | — | 100 | 110.5 (37.4) | 96.2 (26.8) | 14.0 (24.4) | ||||||
| Alirocumab | 75 | 51 | 54.9 (10.1) | 43.1 | — | 100 | 127.7 (58.1) | 99.7 (35.6) | 17.0 (16.3) | ||||||
| Placebo | 0 | 25 | 58.5 (7.8) | 32 | — | 100 | 109.8 (31.4) | 87.0 (21.0) | 12.0 (24.4) | ||||||
| 11 | 2018 | Koh KK | ODYSSEY KT | 24 | LDL-C ≥ 70 mg/dl with a history of documented CVD, or LDL-C ≥ 100 mg/dl without such history | Placebo | 0 | 102 | 60.1 (9.1) | 20.6 | — | 37.3 | 99.3 (25.2) | 85.6 (17.7) | 24.5 (33.3) |
| Alirocumab | 75 | 97 | 61.2 (10.4) | 14.4 | — | 33 | 97.0 (27.8) | 81.7 (17.2) | 23.0 (31.1) | ||||||
| 12 | 2019 | Han Y | ODYSSEY EAST | 24 | LDL-C ≥ 70 mg/dl with CVD or LDL-C ≥ 100 mg/dl without CVD | Alirocumab | 75 | 407 | 58.8 (10.7) | 22.6 | 63.4 | 29.7 | 110.7 (48.5) | 94.7 (28.6) | 28.0 (47.0) |
| Ezetimibe | 0 | 208 | 58.3 (11.2) | 29.8 | 53.4 | 23.1 | 111.2 (49.8) | 95.5 (30.5) | 31.0 (50.0) | ||||||
| Evolocumab | |||||||||||||||
| 13 | 2014 | Blom DJ | DESCARTES | 52 | LDL-C ≥ 75 mg/dl and TG ≤ 400 mg/dl | Placebo | 0 | 129 | 57.0 (10.6) | 21.3 | 39.5 | 7.8 | 98.4 (14.5) | 82.6 (11.0) | 12.1 (28.7) |
| Evolocumab | 420 | 254 | 57.2 (10.3) | 57.1 | 42.9 | 6.7 | 101.3 (15.1) | 84.0 (12.6) | 12.1 (21.3) | ||||||
| Placebo | 0 | 73 | 58.4 (8.7) | 54.8 | 56.2 | 19.2 | 96.2 (13.3) | 83.3 (12.4) | 21.7 (49.1) | ||||||
| Evolocumab | 420 | 145 | 57.8 (9.4) | 47.6 | 57.9 | 13.1 | 94.6 (12.9) | 83.3 (12.5) | 30.8 (52.8) | ||||||
| Placebo | 0 | 63 | 55.9 (9.0) | 47.6 | 60.3 | 25.4 | 119.8 (32.4) | 100.3 (22.1) | 26.3 (65.4) | ||||||
| Evolocumab | 420 | 126 | 54.2 (11.5) | 44.4 | 54 | 19.8 | 116.8 (35.3) | 95.5 (23.6) | 27.9 (48.2) | ||||||
| 14 | 2014 | Robinson JG | LAPLACE-2 | 12 | LDL-C ≥ 80 mg/dl with intensive statin and TG ≤ 400 mg/dl | Placebo | 0 | 56 | 58.3 (10.5) | 42.9 | — | 16.1 | 123.0 (46.6) | 95.3 (26.0) | 13.1 (23.0) |
| Placebo | 0 | 55 | 62.2 (10.4) | 50.9 | — | 12.7 | 123.7 (47.9) | 95.3 (29.6) | 17.1 (28.1) | ||||||
| Ezetimibe | 0 | 56 | 61.0 (9.0) | 51.8 | — | 10.7 | 126.8 (49.6) | 101.3 (31.2) | 15.4 (55.7) | ||||||
| Ezetimibe | 0 | 55 | 60.6 (9.2) | 50.9 | — | 20 | 119.3 (28.1) | 94.6 (20.4) | 13.8 (47.8) | ||||||
| Evolocumab | 140 | 110 | 58.3 (8.4) | 50.9 | — | 20.9 | 124.2 (43.4) | 99.7 (26.4) | 11.3 (34.6) | ||||||
| Evolocumab | 420 | 110 | 59.6 (11.1) | 40 | — | 13.6 | 126.1 (50.4) | 97.3 (28.9) | 20.4 (48.8) | ||||||
| Placebo | 0 | 55 | 57.1 (9.9) | 40 | — | 12.7 | 100.3 (36.2) | 81.1 (22.1) | 24.6 (50.0) | ||||||
| Placebo | 0 | 55 | 58.8 (11.5) | 43.6 | — | 18.2 | 94.7 (31.9) | 80.1 (21.4) | 20.8 (42.9) | ||||||
| Ezetimibe | 0 | 56 | 60.5 (10.2) | 42.9 | — | 17.9 | 98.7 (34.0) | 85.3 (23.1) | 10.4 (29.6) | ||||||
| Ezetimibe | 0 | 54 | 61.1 (8.9) | 51.9 | — | 31.5 | 92.3 (19.3) | 78.7 (16.7) | 25.6 (55.5) | ||||||
| Evolocumab | 140 | 109 | 59.7 (10.2) | 39.4 | — | 14.7 | 94.2 (34.8) | 79.9 (25.1) | 13.3 (38.3) | ||||||
| Evolocumab | 420 | 110 | 60.1 (10.2) | 43.6 | — | 16.4 | 93.8 (32.3) | 77.9 (21.5) | 10.2 (26.3) | ||||||
| Placebo | 0 | 56 | 61.9 (9.7) | 57.1 | — | 17.9 | 110.3 (28.0) | 91.6 (18.4) | 14.2 (46.3) | ||||||
| Placebo | 0 | 55 | 61.5 (10.3) | 50.9 | — | 20 | 108.6 (30.9) | 89.8 (20.7) | 14.6 (44.0) | ||||||
| Evolocumab | 140 | 112 | 59.7 (9.2) | 40.2 | — | 17.9 | 114.9 (34.9) | 94.2 (24.0) | 15.8 (47.5) | ||||||
| Evolocumab | 420 | 115 | 61.5 (9.6) | 51.3 | — | 13 | 123.7 (48.5) | 96.5 (27.5) | 13.3 (50.3) | ||||||
| Placebo | 0 | 58 | 61.2 (9.1) | 60.3 | — | 5.2 | 115.6 (39.8) | 93.1 (27.3) | 14.2 (46.3) | ||||||
| Placebo | 0 | 57 | 59.6 (9.2) | 47.4 | — | 15.8 | 119.9 (39.1) | 95.9 (25.2) | 14.6 (44.0) | ||||||
| Evolocumab | 140 | 113 | 58.9 (11.2) | 45.1 | — | 23 | 118.7 (40.9) | 95.4 (27.0) | 15.8 (47.5) | ||||||
| Evolocumab | 420 | 115 | 59.3 (10.5) | 44.3 | — | 10.4 | 122.9 (42.0) | 97.2 (26.9) | 13.3 (50.3) | ||||||
| Placebo | 0 | 56 | 60.2 (8.7) | 37.5 | — | 3.6 | 77.4 (20.9) | 71.0 (16.6) | 11.9 (50.6) | ||||||
| Placebo | 0 | 55 | 58.1 (11.4) | 47.3 | — | 10.9 | 102.9 (49.3) | 84.8 (29.7) | 13.8 (42.3) | ||||||
| Evolocumab | 140 | 111 | 59.5 (9.2) | 38.7 | — | 16.2 | 88.5 (31.5) | 77.4 (22.3) | 17.1 (53.4) | ||||||
| Evolocumab | 420 | 112 | 59.6 (9.0) | 46.4 | — | 10.7 | 88.5 (31.3) | 78.7 (23.1) | 20.6 (53.5) | ||||||
| 15 | 2015 | Raal FJ | TESLA Part B | 12 | HoFH | Placebo | 0 | 16 | 32 (14) | 50 | — | — | 335.9 (146.7) | 210.0 (80.0) | 53.3 (37.3) |
| Evolocumab | 420 | 33 | 30 (12) | 48 | — | — | 355.2 (135.1) | 210.0 (70.0) | 31.7 (36.7) | ||||||
| 16 | 2015 | Raal FJ | RUTHERFORD-2 | 12 | HeFH | Placebo | 0 | 54 | 51.1 (14.2) | 46 | — | — | 150.6 (34.7) | 110.0 (30.0) | 18.3 (25.0) |
| Evolocumab | 140 | 110 | 52.6 (12.3) | 40 | — | — | 154.4 (50.2) | 120.0 (30.0) | 32.3 (54.5) | ||||||
| Placebo | 0 | 55 | 46.8 (12.1) | 44 | -— | — | 150.6 (42.5) | 110.0 (20.0) | 36.3 (56.5) | ||||||
| Evolocumab | 420 | 110 | 51.9 (12.0) | 42 | — | — | 154.4 (42.5) | 110.0 (30.0) | 25.4 (54.6) | ||||||
| 17 | 2016 | Kiyosue A | YUKAWA-2 | 12 | LDL-C ≥ 100 mg/dl and TG ≤ 400 mg/dl | Placebo | 0 | 202 | 61.0 (10.0) | 39 | 72 | 51 | 103.0 (28.0) | 92.0 (20.0) | 12.9 (11.7) |
| Evolocumab | 140/420 | 202 | 62.0 (11.0) | 40 | 75 | 47 | 109.0 (35.0) | 96.0 (25.0) | 14.2 (14.5) | ||||||
| 18 | 2017 | Sabatine MS | FOURIER | 12 | LDL-C ≥ 70 mg/dl with atherosclerotic vascular disease or LDL-C ≥ 100 mg/dl without atherosclerotic vascular disease | Evolocumab | 140/420 | 13,784 | 32.5 (9.1) | 24.6 | 80.1 | 36.7 | 92 (21.5) | — | 15.4 (47.2) |
| Placebo | 0 | 13,780 | 62.5 (8.9) | 24.5 | 80.1 | 36.5 | 92 (21.5) | — | 15.4 (46.6) | ||||||
| 19 | 2019 | Lorenzatti AJ | BERSON | 12 | LDL-C ≥100 mg/dl with DM | Evolocumab | 140/420 | 657 | 62 (34.8) | 55.9 | 72.8 | 100 | 92.8 (34.8) | — | 28.9 (39.3) |
| Placebo | 0 | 324 | 62 (33.3) | 60.2 | 73.8 | 100 | 92.8 (30.9) | — | 28.9 (39.0) | ||||||
| 20 | 2019 | Rosenson RS | BANTING | 12 | LDL-C ≥70 mg/dl and non-HDL-C ≥100 mg/dl with DM and CVD, or LDL-C ≥100 mg/dl and non-HDL-C ≥130 mg/dl with DM and without CVD | Evolocumab | 420 | 280 | 62.5 (8.5) | 42.9 | 88.2 | 100 | 108.7 (30.9) | 97.0 (23.0) | 36.7 (46.5) |
| Placebo | 0 | 141 | 62.2 (8.4) | 46.1 | 84.4 | 100 | 110.6 (32.9) | 98.0 (22.0) | 41.4 (51.2) | ||||||
| Inclisiran | |||||||||||||||
| 21 | 2020 | Raal FJ | ORION-9 | 78 | LDL-C ≥100 mg/dL with FH | Inclisiran | 300 | 242 | 56 (11.9) | 53.7 | 42.1 | 8.3 | 151.4 (50.4) | 123.8 (33.2) | 23.8 (65.8) |
| Placebo | 0 | 240 | 56 (13.3) | 52.1 | 42.1 | 11.7 | 154.7 (58.0) | 124.5 (34.8) | 22.5 (68.8) | ||||||
| 22 | 2020 | Raal KK | ORION-10 | 78 | LDL-C ≥70 mg/dl with ASCVD | Inclisiran | 300 | 781 | 66.4 (8.9) | 31.5 | 91.4 | 47.5 | 104.5 (39.6) | 94.1 (25.6) | 23.8 (72.1) |
| Placebo | 0 | 780 | 65.7 (8.9) | 29.7 | 89.9 | 42.4 | 104.8 (37.0) | 94.6 (25.1) | 23.3 (70.4) | ||||||
| ORION-11 | LDL-C ≥70 mg/dl with ASCVD factors | Inclisiran | 300 | 810 | 64.8 (8.3) | 28.5 | 79 | 36.5 | 107.2 (41.8) | 97.1 (28.0) | 17.5 (66.7) | ||||
| Placebo | 0 | 807 | 84.8 (8.7) | 28 | 81.9 | 33.7 | 103.7 (36.4) | 95.1 (5.2) | 14.6 (67.9) | ||||||
HP: hypertension; DM: type 2 diabetes mellitus; LDL-C: low-density lipoprotein cholesterol; ApoB: apolipoprotein B; Lp(a): lipoprotein(a).