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AimHigh-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo.ObjectiveTo investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA).Design and settingA 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.PatientsFive hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively.InterventionPatients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001.Main outcome measuresThe 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.ResultsThe nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 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.ConclusionCER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;Trial registration numberNCT01201837.

Background Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment.Methods In a randomized, placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset (<48h) we compared the effects of treatment with continuous intravenous amiodarone 125mg per hour (total 3g) and intravenous placebo. Patients in the placebo group who did not convert to normal sinus rhythm within 24h were started on amiodarone therapy.Results Conversion to normal sinus rhythm occurred within 24h in 32 of 50 patients (64%) in the placebo group, most of whom converted within 8h. Lower conversion rates were observed in patients with hypertension, ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45mm, ejection fraction below 45% or significant mitral regurgitation. However, in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present. In such patients the spontaneous conversion rate was approximately 90%. The conversion rate during 24h of treatment in the amiodarone group was 92% (P=0·0017, compared to the placebo group). In this group, the conversion rate was largely unaffected by baseline characteristics. Of the 18 patients who did not convert with placebo, 15 (85%) converted after being crossed over to amiodarone. All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month. In patients still in atrial fibrillation after 8h of treatment, the pulse rate decreased significantly more in the amiodarone as compared to the placebo group (83±15 vs 114±20 beats.min−1,P =0·0014).Conclusion The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90% in specific clinical and echocardiographically defined subgroups. Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation. However, such treatment should be reserved for patients with unfavourable risk factor profiles, not converting during 8h of observation or requiring rate control. [ABSTRACT FROM PUBLISHER]