Table 2.
Changes from baseline in cholesterol content of LDL subfractions
| Study 565 | Study 566a | Study 1003 | |||||
|---|---|---|---|---|---|---|---|
| Placebo | Alirocumab 150 mg Q2W | Placebo + ATV 80 mg | Alirocumab 150 mg Q2W + ATV 10 mg | Alirocumab 150 mg Q2W + ATV 80 mg | Placebo | Alirocumab 150 mg Q2W | |
| n = 31 | n = 29 | n = 26 | n = 26 | n = 29 | n = 14 | n = 16 | |
| Total LDL-C | |||||||
| Baseline | 115.2 (27.3) | 109.6 (24.8) | 120.1 (24.4) | 123.0 (24.0) | 122.1 (33.4) | 141.4 (34.1) | 135.7 (28.2) |
| Post-treatmentb | 111.1 (25.1) | 34.5 (14.9) | 97.7 (37.7) | 43.5 (15.3) | 44.6 (25.5) | 130.4 (32.0) | 53.4 (34.2) |
| % change from baseline | −1.1 (21.3) | −67.5 (13.6)** | −17.3 (29.9) | −64.6 (11.9)** | −62.2 (22.5)** | −6.9 (13.7) | −60.3 (25.8)** |
| LDLr-C | |||||||
| Baseline | 90.5 (25.0) | 85.6 (22.5) | 95.0 (22.3) | 96.9 (21.7) | 96.0 (29.2) | 110.3 (28.9) | 103.6 (24.1) |
| Post-treatmentb | 87.2 (21.6) | 21.5 (12.5) | 75.9 (32.4) | 27.7 (12.6) | 29.6 (22.5) | 100.6 (24.4) | 36.8 (29.9) |
| % change from baseline | 0.1 (24.6) | −74.9 (14.4)** | −18.6 (32.5) | −71.6 (11.5)** | −68.7 (22.9)** | −7.1 (15.5) | −64.7 (28.6)** |
| LDL1-C | |||||||
| Baseline | 18.7 (6.3) | 16.2 (5.6) | 19.8 (7.0) | 19.2 (7.7) | 19.7 (9.2) | 23.3 (10.2) | 25.9 (9.9) |
| Post-treatmentb | 17.0 (6.9) | 3.6 (2.8) | 14.7 (9.2) | 5.3 (3.5) | 4.9 (4.9) | 21.9 (10.8) | 6.8 (6.2) |
| % change from baseline | −7.5 (24.4) | −76.9 (20.8)** | −18.4 (59.4) | −72.5 (16.4) | −40.7 (201.0) | 1.0 (39.1) | −68.9 (41.3)** |
| LDL2-C | |||||||
| Baseline | 22.3 (11.7) | 20.3 (10.9) | 29.4 (13.8) | 24.5 (12.3) | 27.6 (15.6) | 30.7 (17.5) | 31.5 (17.1) |
| Post-treatmentb | 17.8 (12.5) | 3.0 (4.4) | 21.5 (16.1) | 4.5 (4.9) | 5.5 (8.4) | 27.5 (13.7) | 7.8 (11.9) |
| % change from baseline | 2.9 (140.9) | −84.2 (26.2)* | −24.7 (48.5) | −83.7 (13.0)** | −83.4 (20.0)** | −2.6 (39.1) | −77.9 (26.1)** |
| LDL3-C | |||||||
| Baseline | 39.1 (15.2) | 37.1 (13.5) | 37.6 (14.8) | 40.6 (14.0) | 37.2 (16.4) | 43.7 (13.2) | 36.6 (12.5) |
| Post-treatmentb | 38.2 (12.2) | 9.1 (6.6) | 30.5 (13.2) | 11.0 (6.3) | 11.7 (10.1) | 39.9 (12.0) | 15.2 (12.8) |
| % change from baseline | 4.7 (31.6) | −74.8 (20.4)** | −5.5 (63.5) | −71.5 (18.0)** | −64.9 (29.7)** | −5.0 (25.9) | −58.1 (33.9)** |
| LDL4-C | |||||||
| Baseline | 10.4 (7.1) | 12.1 (9.0) | 8.3 (6.4) | 12.7 (8.5) | 11.6 (11.6) | 12.7 (9.7) | 9.7 (11.4) |
| Post-treatmentb | 14.2 (9.2) | 5.8 (2.5) | 9.2 (5.0) | 7.0 (3.1) | 7.5 (4.0) | 11.2 (6.7) | 7.1 (3.5) |
| Absolute change from baseline | 3.9 (8.5) | −6.2 (8.4)** | 0.9 (4.7) | −5.7 (6.5)* | −4.1 (9.3)* | −1.4 (7.5) | −2.6 (9.7)* |
| % change from baseline | 84.7 (164.0) | −28.6 (56.4)* | 106.2 (236.9) | −5.6 (133.5) | 51.3 (352.1) | 12.8 (67.4) | 53.7 (156.8) |
| LDL1+2-C | |||||||
| Baseline | 40.9 (16.6) | 36.5 (13.9) | 49.1 (17.5) | 43.6 (17.9) | 47.2 (21.5) | 54.0 (25.2) | 57.4 (24.9) |
| Post-treatmentb | 34.8 (17.8) | 6.6 (6.2) | 36.2 (24.2) | 9.8 (7.9) | 10.4 (12.0) | 49.4 (21.5) | 14.7 (17.6) |
| % change from baseline | −10.3 (41.2) | −81.0 (18.9)** | −22.6 (51.5) | −78.8 (13.1) | −22.4 (312.6) | −1.8 (28.9) | −74.2 (30.6)** |
| LDL3+4-C | |||||||
| Baseline | 49.5 (18.1) | 49.2 (19.6) | 45.9 (18.0) | 53.2 (18.0) | 48.8 (26.1) | 56.4 (19.9) | 46.3 (22.7) |
| Post-treatmentb | 52.4 (15.8) | 14.9 (8.1) | 39.7 (14.1) | 18.0 (7.8) | 19.2 (13.4) | 51.1 (16.1) | 22.3 (14.5) |
| % change from baseline | 15.0 (41.4) | −68.5 (18.0)** | −0.9 (57.9) | −64.1 (18.8)** | −55.2 (30.8)** | −4.5 (27.3) | −48.8 (31.2)** |
Values are mean (SD). Units are mg/dL. *p < 0.05; **p < 0.0001. aPatients in study 566 were randomised to one of three arms and received either (1) placebo with increase in ATV dose from 10 mg to 80 mg at start of randomised treatment period, (2) alirocumab plus ATV 10 mg, or (3) alirocumab with increase in ATV dose from 10 mg to 80 mg at start of randomised treatment period. bMeasurements occurred on Week 12 in Study 565, Week 8 in study 566 and Week 6 in study 1003. Q2W every 2 weeks, ATV atorvastatin, IDL intermediate-density lipoprotein, LDL-C low density lipoprotein cholesterol, LDLr “LDL real” [i.e. total LDL fraction minus Lp(a) and IDL], Lp(a) lipoprotein (a), SD, standard deviation