| A phase 3 clinical trial ACCELERATE (NCT01687998) |
CETP inhibitor (evacetrapib) |
|
[74] |
| A randomized, double-blind study involving 15,067 patients at high cardiovascular risk |
Torcetrapib plus atorvastatin, or atorvastatin alone |
-
✓
Increase of 72.1% in HDL-C and decrease of 24.9% in LDL-C, as compared with baseline (p < 0.001 for both).
-
✓
Increased risk of CV events (HR, 1.25; 95% CI, 1.09–1.44; p = 0.001) and death from any cause (HR, 1.58; 95% CI, 1.14–2.19; p = 0.006).
|
[75] |
| A randomized study involving 15,871 patients with a recent acute coronary syndrome |
CETP inhibitor (dalcetrapib) at a dose of 600 mg daily, or placebo |
-
✓
Increase in HDL-C levels from baseline by 31–40% in the dalcetrapib group; minimal effect on LDL cholesterol levels.
-
✓
No change in the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; HR, 1.04; 95% Cl, 0.93–1.16; p = 0.52).
-
✓
No significant effect on any component of the primary end point or total mortality.
|
[76] |
| Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) double-blind, placebo-controlled clinical trial involving 30,449 adults with atherosclerotic vascular disease |
100 mg of anacetrapib once daily, or matching placebo |
-
✓
Increase in mean HDL-C level by 1.12 mmol/L vs. placebo (relative difference of 104%), decrease in mean non-HDL-C level by 0.44 mmol/L (relative difference of −18%).
-
✓
Decrease in the incidence of major coronary events, compared with placebo (10.8% vs. 11.8%; RR, 0.91; 95% Cl, 0.85–0.97; p = 0.004).
-
✓
Unknown whether this effect was associated with the rise in HDL-C cholesterol, the decrease in non-HDL-C, or the use of statins.
|
[77] |
| A randomized placebo-controlled trial conducted at 17 centres in Canada. |
4 weekly infusions of placebo (saline), or 40 mg/kg of reconstituted HDL (CSL-111), or 80 mg/kg of CSL-111 |
-
✓
The percentage change in atheroma volume was −3.4% with CSL-111 and −1.6% for placebo (p = 0.48 between groups, p < 0.001 vs. baseline for CSL-111). The nominal change in plaque volume was −5.3 mm3 with CSL-111 and −2.3 mm3 with placebo (p = 0.39 between groups, p < 0.001 vs. baseline for CSL-111).
-
✓
Discontinuation of higher-dosage CSL-111 treatment due to liver function test abnormalities; CSL-111 40 mg/kg resulted in mild, self-limiting transaminase elevation (clinically well-tolerated).
|
[82,83] |
| A randomized, placebo-controlled AIM-HIGH clinical trial (NCT00120289) including 3414 patients |
Extended-release niacin, 1500–2000 mg/day, or matching placebo; all patients received simvastatin, 40–80 mg per day, plus ezetimibe, 10 mg per day, if needed |
-
✓
At 2 years, a significant increase in median HDL-C level from 0.91 mmol/L to 1.08 mmol/L, decrease in TG level from 1.85 mmol/L to 1.38 mmol/L and reduced LDL-C level from 1.91 mmol/L to 1.60 mmol/L.
-
✓
The primary end point occurred in 16.4% of patients in the niacin group and 16.2% in the placebo group (HR, 1.02; 95% Cl, 0.87–1.21; p = 0.79, by the log-rank test).
-
✓
No clinical benefit from niacin + statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.
|
[85] |
