VRN

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2–5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCAmeasurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was 22.71, 23.13, 21.50, and 23.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P ¼ 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, 20.02, 0.01, and 0.19%; nominal P ¼ 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was 20.022, 20.036, 20.022, and 20.015 mm (nominal P ¼ 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis scorewas 20.51, 2.65, 0.71, and 20.77% (compared with placebo, nominal P ¼ 0.85 for 12 mg/kg and nominal P ¼ 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCAwhen compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study.