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Ash In the ARBITER 6-HALTS trial (N Engl J Med 2009 Nov 26;361(22):2113 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=19915217> ) which you noted niacin was compared to ezetimibe in patients on long-term statin therapy. In a per-protocol analysis a composite outcome of major cardiovascular events was lower with niacin (1%) than with ezetimibe (5%). I don’t know what that means for the clinical efficacy of ezetimibe (or for niacin because this trial did not have a placebo control), but it suggests that niacin appears better than ezetimibe in terms of comparative efficacy. Thanks for noting the AIM-HIGH trial. We will consider summarizing the NIH news release as the results are not published yet. Looks like it is interpreted as niacin have no clinical benefit in the context of patients with well-controlled LDL cholesterol levels. And a subset of AIM-HIGH trial participants used ezetimibe in addition to the statin. Brian Brian S. Alper, MD, MSPH Editor-in-Chief, DynaMed (www.ebscohost.com/dynamed) From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Ash Paul Sent: Sunday, August 21, 2011 8:24 AM To: [log in to unmask] Subject: Re: Ezetimibe/Simvastatin and clinical outcomes Dear Brian, What about the extended-release Niacin versus Ezetimibe trial published in the NEJM in November 2009? http://www.nejm.org/doi/full/10.1056/NEJMoa0907569 Not that Niacin itself is as white as the driven snow - On Thursday 5/26/11 the National Heart, Lung, and Blood Institute of the National Institutes of Health stopped the AIM HIGH trial of 3414 subjects on Niacin after 32 months, 18 months prematurely. The NIH stated, that in conjunction with statin treatment, high dose niacin to raise HDL (“good cholesterol”) and control triglycerides, “did not reduce the risk of cardiovascular events, including heart attacks and stroke. In fact a slight (1.6%) increase in stroke was seen. Regards, Ash From: Brian Alper MD <[log in to unmask]> To: [log in to unmask] Sent: Sunday, 21 August 2011, 12:57 Subject: Ezetimibe/Simvastatin and clinical outcomes Fascinating dialog regarding ezetimibe and ENHANCE trial. First ezetimibe was released and the only outcomes available to support it were surrogate (lipid levels) so the conclusion for many was no clinical evidence to support its use. Then the ENHANCE trial showed no benefit with a “more important” surrogate outcome. Then the SEAS trial (N Engl J Med 2008 Sep 25;359(13):1343 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list%5Fuids=18765433&> ) came out and found no significant difference in overall rate of cardiovascular events in patients with aortic stenosis. Now the SHARP trial (Lancet 2011 Jun 25;377(9784):2181 <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list%5Fuids=21663949&> ) was published in June and found a significant difference in patients with chronic kidney disease. Challenges with this trial include: 1) Difference within composite outcome appears isolated to ischemic stroke and coronary revascularization outcomes, so not clear how useful the composite outcome conclusion is 2) Change in composite outcome definition used for primary outcome occurred between original protocol and final publication 3) Change in which patients were analyzed occurred between original protocol and final publication (this is because a third arm included simvastatin alone for 1 year then re-randomized to the ezetimibe/simvastatin or placebo groups --- whether or not these patients were analyzed changed) 4) No comparison with simvastatin alone so unable to determine if the ezetimibe component has any clinical relevance Brian S. Alper, MD, MSPH Editor-in-Chief, DynaMed (www.ebscohost.com/dynamed)