PCSK9 shows benefit in cholesterol lowering

Despite the potency of high dose statins, many patients fail to reach targets for low-density lipoprotein (LDL) cholesterol reduction. Whilst the addition of a second agent such as niacin or ezetemibe results in an additional 10–20% reduction in cholesterol, there remains an unmet need for more potent therapies. Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing their degradation and reducing the rate at which LDL cholesterol is removed from the circulation. The injectable fully human monoclonal antibody SAR236553 binds PCSK9, resulting in increases in LDL receptor recycling and reductions in LDL cholesterol. In this phase 2, multicenter, double-blind, placebo-controlled trial 92 patients who had LDL cholesterol levels of 2.6 mmol/l or higher despite statin therapy were randomised to 8 weeks treatment with atorvastatin 80 mg plus SAR236553 fortnightly, atorvastatin 10 mg plus SAR236553, or atorvastatin 80 mg plus placebo injections. The primary end-point was the change in LDL at 8 weeks. The least-squares mean (±SE) percent reduction in LDL was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (p<0.001) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553 (p<0.001). All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of less than 2.6 mmol/l and at least 90% of patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of less than 1.8 mmol/l. There were no significant differences in adverse events seen between SAR236553 and placebo.

Fish oils don't decrease post-pp atrial fibrillation

Both clinical and experimental evidence have suggested an anti-arrhythmic effect of long-chain n-3 polyunsaturated fatty acids (n-3-PUFAs) in fish oil. However, the effect of n-3-PUFAs on atrial arrhythmias such as postoperative atrial fibrillation (AF) remain uncertain. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) trial was designed to test whether perioperative n-3-PUFA supplementation could reduce postoperative AF.

One thousand and five hundred and sixteen patients scheduled for cardiac surgery in 28 centres in the USA, Italy, and Argentina were enrolled between August 2012 and June 2012. Patients were randomised to receive fish oil or placebo, with preoperative loading of 10 g over 3–5 days, followed postoperatively by 2 g per day until hospital discharge or postoperative day first, whichever was sooner. Patients not in sinus rhythm at the outset were excluded. The main outcome measure was the occurrence of postoperative AF lasting longer than 30 s.

233 (30.7%) of patients assigned to placebo developed postoperative AF compared to 227 (30.0%) assigned to n-3 PUFAs (p=0.74). The number of postoperative AF episodes also did not differ between the placebo and PUFA groups, nor did the incidence of AF that was sustained, symptomatic, or treated (p=0.70). However, supplementation with n-3 PUFAs was generally well tolerated, and there was no suggestion of increased bleeding or serious adverse events.

Catheter ablation for paroxysmal AF

AF is the commonest cardiac arrhythmia. While a number of established drug therapies are often successful in achieving satisfactory control, more recently radio frequency catheter ablation has emerged as an effective therapy for patients with paroxysmal AF. However, the place of catheter ablation remains unclear with limited data comparing ablation with antiarrhythmic drug therapy as first-line treatment in patients.

In the MANTRA-PAF trial 294 patients (mean age 55) with new onset paroxysmal AF and no history of antiarrhythmic drug use were randomly assigned to an initial strategy of either catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up was by 7-day Holter-monitoring at 3, 6, 12, 18, and 24 months. The primary end points were the cumulative and per-visit burden of AF (ie, percentage of time in AF). During follow-up there was no significant difference between ablation and drug-therapy in cumulative AF burden (90th percentile of arrhythmia burden, 13% and 19%, respectively; p=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of AF was significantly lower in the ablation group (90th percentile, 9% vs 18%; p=0.007), and more patients in the ablation group were free from any AF (85% vs 71%, p=0.004) and from symptomatic AF (93% vs 84%, p=0.01). However, this slight improvement came at the price of one death in the ablation group due to a procedure-related stroke and there were also three cases of cardiac tamponade.