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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
  1. Data are mean (SD), mean (SE), number (%), or median (IQR); lipid profiles are mean (SE) if not indicated; age is mean (SD). DESCARTES, the Durable Effect of PCSK9 Antibody Compared with Placebo Study trial; GAUSS, the Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects trial; LAPLACE-TIMI 57, the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial; MENDEL, Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels trial; OSLER, the Open Label Study of Long Term Evaluation Against LDL-C trial; RUTHERFORD, The Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder trial; TESLA, The Trial Evaluating PCSK9 Antibody in Subjects with LDL Receptor Abnormalities; YUKAWA, the StudY of LDL-Cholesterol Reduction Using a Monoclonal PCSK9 Antibody in Japanese Patients With Advanced Cardiovascular Risk trial
  2. CHD, coronary heart disease; CVD, cardiovascular disease; DM, diabetes mellitus; HDL-C, high-density lipoprotein (HDL) cholesterol; HeFH, heterozygous familial hypercholesterolemia IQR, interquartile range; LDL-C, low-density lipoprotein (LDL) cholesterol; LLT, lipid-lowering therapy; NA, not applicable; PCSK9, proprotein convertase subtilisin/kexin type 9; SD, standard deviation; SE, standard error; Total-C, total cholesterol