Table 1 Baseline characteristics of included randomized trials
From: Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials
Trial/first author | Year | Number | Follow-up, weeks | Age, years | Women, number (%) | LDL-C, mmol/L | Total-C, mmol/L | HDL-C, mmol/L | Free PCSK9, nmol/L | Statin use, number (%) | Ezetimibe use, number (%) | CHD, number (%) | DM, number (%) | Patient profile and background lipid-lowering therapy |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RUTHERFORD | 2012 | 167 | 12 | 50 (13) | 79 (47) | 4.0 (1.1) | 6.1 (1.3) | 1.3 (0.4) | 8.3 (2.4) | 150 (89) | 108 (64) | 35 (21) | NA | HeFH with LDL-C ≥2.6 mmol/L. Statin ± ezetimibe |
LAPLACE-TIMI 57 | 2012 | 629 | 12 | 62 (55, 67) | 320 (51) | 3.2 (0.7) | 5.2 (0.9) | 1.4 (0.4) | 6.2 (1.7) | 627 (99) | 57 (9) | 187 (30) | 103 (16) | LDL-C ≥2.2 mmol/L and triglycerides ≤4.5 mmol/L. Statin ± ezetimibe |
GAUSS | 2012 | 157 | 12 | 62 (8) | 100 (64) | 5.0 (1.3) | 7.3 (1.4) | 1.5 (0.5) | 5.3 (1.4) | 0 | 64 (40) | 21 (13.4) | NA | LDL-C ≥2.6 mmol/L with diagnosed CHD or risk equivalent; ≥3.4 mmol/L without CHD or risk equivalent and 2 or more risk factors, or ≥4.1 mmol/L without CHD or risk equivalent and with 1 or 0 risk factors. No/low-dose statin or statin-intolerance |
MENDEL | 2012 | 406 | 12 | 51 (12) | 267 (66) | 3.7 (0.6) | 5.7 (0.8) | 1.4 (0.4) | 4.8 (1.2) | 0 | 45 (11) | 0 | 1 (0.2) | LDL-C ≥2.6 and <4.9 mmol/L and triglycerides ≤4.5 mmol/L, and a 10 year Framingham risk score for coronary heart disease of up to 10 %. No background anti-lipid therapy |
YUKAWA | 2014 | 307 | 12 | 62 (10) | 114 (37) | 3.7 (0.5) | 5.8 (0.6) | 1.4 (0.3) | 5.6 (1.8) | 307 (100) | NA | 77 (25) | 117 (38) | LDL-C ≥3.0 mmol/L and triglycerides ≤4.5 mmol/L high risk for cardiovascular events. Statin ± ezetimibe |
MENDEL-2 | 2014 | 614 | 12 | 54 (10) | 423 (69) | 3.6 (0.5) | NA | 1.5 (1.1, 2.0) | 3.9 (1.2) | 0 | 154 (25) | 0 | 1 (0.1) | LDL-C ≥2.6 and <4.9 mmol/L, triglycerides ≤4.5 mmol/L, and 10-year Framingham coronary heart disease risk scores ≤ 10 %. No lipid regulating drugs within 3 months |
LAPLACE-2 | 2014 | 1896 | 12 | 60 (10) | 868 (46) | 2.8 (1.0) | 4.9 (1.1) | 1.4 (0.4) | 4.9 (1.6) | 1327 (70) | NA | 427 (23) | 293 (16) | LDL-C ≥3.9 mmol/L (no statin at screening), ≥2.6 mmol/L (nonintensive statin at screening), or ≥2.1 mmol/L (intensive statin at screening) and triglyceride ≤4.5 mmol/L |
GAUSS-2 | 2014 | 307 | 12 | 62 (10) | 141 (46) | 5.0 (1.5) | NA | 1.3 (0.5) | 4.4 (1.7) | 55 (18) | NA | NA | 62 (20) | LDL-C ≥ 2.6 mmol/L and triglycerides ≤4.5 mmol/L. No/low-dose statin or statin-intolerance |
DESCARTES | 2014 | 901 | 52 | 57 (10) | 471 (52) | 2.7 (0.6) | 4.6 (0.7) | 1.4 (0.4) | 6.7 (2.2) | 790 (88) | 189 (21) | 136 (15) | 104 (12) | LDL-C ≥1.9 mmol/L and triglycerides ≤4.5 mmol/L. Statin ± ezetimibe |
OSLER | 2014 | 1104 | 52 | 57 (12) | 610 (55) | 3.7 (1.0) | 5.8 (1.2) | 1.4 (0.4) | 5.8 (2.1) | 691 (63) | NA | 210 (19) | 109 (10) | From parent studies (RUTHERFORD, LAPLACE-TIMI 57, GAUSS, MENDEL) |
TESLA | 2014 | 49 | 12 | 31 (13) | 24 (49) | 9.0 (3.5) | NA | 1.0 (0.3) | 9.0 (2.7) | 49 (100) | 45 (92) | 21 (43) | NA | Homozygous familial hypercholesterolaemia, LDL-C ≥3.4 mmol/L. Statin ± ezetimibe |
RUTHERFORD-2 | 2014 | 329 | 12 | 51 (14) | 139 (42) | 3.9 (1.0) | NA | 1.4 (0.4) | 6.0 (1.7) | 329 (100) | 204 (62) | 103 (31) | NA | HeFH patients ≥2.6 mmol/L. Statin ± ezetimibe |
McKenney | 2012 | 183 | 12 | 57 (10) | 96 (53) | 3.4 (0.7) | 5.4 (0.7) | 1.3 (0.3) | NA | NA | NA | 10 (6) | 22 (12) | LDL-C ≥2.6 mmol/L on stable-dose atorvastatin for ≥6 weeks |
Stein | 2012 | 77 | 12 | 53 (10) | 30 (39) | 3.9 (0.9) | 6.1 (1.0) | 1.4 (0.3) | NA | 77 (100) | 55 (71) | 32 (42) | 3 (4) | HeFH and LDL-C ≥2.6 mmol/L. Statin ± ezetimibe |
Roth | 2012 | 92 | 8 | 57 (10) | 55 (60) | 3.2 (0.5) | 5.2 (0.7) | 1.4 (0.4) | NA | 92 (100) | NA | 3 (3) | 14 (15) | LDL-C ≥2.6 mmol/L on stable-dose atorvastatin for ≥7 weeks |
ODYSSEY COMBO II | 2014 | 720 | 24 | 61 (9) | 530 (74) | 2.7 (0.9) | NA | NA | NA | 719 (99.9) | NA | 580 (81) | 221 (31) | LDL-C ≥1.8 mmol/L (history of CVD) or ≥2.6 mmol/L (no history of CVD) High CV-risk patients on max-tolerated statin |
ODYSSEY FH I | 2014 | 486 | 24 | 52 (12) | 212 (55) | 3.7 (1.2) | NA | NA | NA | 486 (100) | 277 (57) | 225 (46) | 56 (12) | HeFH, inadequately controlled on maximally tolerated stable statin therapy with or without other LLT |
ODYSSEY FH II | 2014 | 249 | 24 | 53 (13) | 118 (47) | 3.5 (1.1) | NA | NA | NA | 249 (100) | 165 (66) | 88 (35) | 10 (4) | HeFH, inadequately controlled on maximally tolerated stable statin therapy with or without other LLT |
ODYSSEY LONG TERM | 2014 | 2341 | 24 | 61 (10) | 884 (38) | 3.2 (1.1) | NA | NA | NA | 2339 (99.9) | 334 (14) | 1607 (69) | 809 (35) | HeFH or High-CV risk patients LDL-C ≥1.8 mmol/L on max-tolerated statin therapy with or without other LLT |
ODYSSEY MONO | 2014 | 103 | 24 | 60 (5) | 48 (47) | 3.6 (0.6) | 5.8 (0.8) | 1.6 (0.5) | NA | 0 | 0 | NA | 4 (4) | LDL-C ≥2.6 and <4.9 mmol/L, 10-year risk of fatal cardiovascular events ≥1 % and ≤5 % |
ODYSSEY ALTERNATIVE | 2014 | 251 | 24 | 63 (10) | 114 (45) | 5.0 (1.8) | NA | 1.3 (0.4) | NA | NA | NA | 118 (47) | 60 (24) | Statin intolerant patients (by medical history) with LDL-C ≥70 mg/dl (very-high CV risk) or ≥ 100 mg/dl (moderate/high risk) |
ODYSSEY COMBO I | 2014 | 316 | 24 | 63 (9) | 108 (34) | 2.7 (0.9) | NA | 1.3 (0.3) | NA | 315 (100) | 26 (8) | 247 (78) | 136 (43) | High CV risk on maximally tolerated statin with or without other LLT (LDL-C ≥70 mg/dl manifest CVD; or LDL-C ≥100 mg/dl with DM and other risk factors or CKD) |
ODYSSEY HIGH FH | 2014 | 107 | 24 | 52 (11) | 50 (47) | 5.2 (1.1) | NA | NA | NA | 107 (100) | 26 (24) | 53 (50) | 15 (14) | HeFH inadequately controlled on maximally tolerated stable statin therapy with or without other LLT (LDL-C ≥160 mg/dl) |
ODYSSEY OPTION I | 2014 | 205 | 24 | 66 (9) | 75 (36) | 2.6 (0.8) | NA | NA | NA | 182 (100) | NA | NA | NA | Patients with prior CVD + LDL-C ≥70 mg/dl, or CV risk factors + LDL-C ≥100 mg/dl |
ODYSSEY OPTION II | 2014 | 204 | 24 | 60 (10) | 88 (43) | 2.7 (1.1) | NA | NA | NA | 175 (100) | NA | NA | NA | Patients with prior CVD + LDL-C ≥70 mg/dl, or CV risk factors + LDL-C ≥100 mg/dl |