November 16th, 2009
ARBITER 6-HALTS: Will you change your practice? Will you halt your use of ezetimibe?
JoAnne M. Foody, MD
ARBITER 6-HALTS provides provocative information and suggests that niacin is the preferred secondary agent once statin therapy is maxed out in high-risk CAD patients with low HDL levels (for the study, go here; for editorials, go here and here; for a summary and analysis of the study, go here; and for a question-and-answer session with the author, go here). For me, however, until outcome studies confirm these findings, we cannot lose focus on the fact that LDL is the primary target of preventive therapy . Nor can we lose focus on all of the other evidence-based approaches that definitively provide benefit including ASA, hypertension control, and smoking cessation.
DISCLOSURE: Dr. Foody is a consultant to and on the advisor’s and speaker’s boards for Merck & Co.
5 Responses to “ARBITER 6-HALTS: Will you change your practice? Will you halt your use of ezetimibe?”
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Absolutely agree – multifactorial approach to risk reduction, LDL reduction emphasis, and await outcomes studies. However, until these outcomes studies are completed, given the totality of the evidence for ezetimibe at this point, it would be very difficult for me to start anyone on this agent. For me, the ARBITER 6-HALTS only adds a small amount of evidence for Niacin – the hard outcomes results are intriguing but the study design and early cessation of the trial temper the strength of it. However, niacin remains a viable alternative for those who have not met LDL goals despite maximum statin therapy (which was not a criterion for ARBITER 6-HALTS). Treating HDL may be reasonable but should be secondary at this point.
I completely agree that outcome studies are a must. However, how do you think these findings will affect recruitment in the ongoing outcome-based IMPROVE-IT study?
Will we ever be able to answer the ezetimibe question with an outcomes study……..
Dr. Lam raises an excellent point. We must, as a scientific community, make a commitment to clinical trials and an evidence-based approach to clinical care..
My hope and belief is that IMPROVE-IT will continue. As a community, we must support this endeavor so as to answer clinically significant questions to the best of our ability with the best tool available, a large-scale, randomized clinical trial.
We have many examples where observational data, small studies with surrogate endpoints have lead us astray.
ARBITER 6 rationale
Thanks for the comments! Agree with Dr. Foody that we need IMPROVE-IT to run to completion, and it would be good for the field to have that trial show meaningful outcomes benefit as LDL treatment alternatives are needed for some patients. Same can be easily said for AIM HIGH testing the niacin/outcomes hypothesis. A little insight into the conception of ARBITER 6- which provides some insight into the difficulty clinicians have in making treatment choices without comparative clinical trials. When ARBITER 2 was presented at AHA in 2004 (comparing niacin to placebo when added to statin monotherapy for IMT change over 12 months) the discussant comments were essentially “interesting, but LDL is primary focus of therapy and this trial doesn’t tell us how a niacin approach would compare to LDL intensification”. That comment was the impetus for ARBITER 6, which provides at least 1 basis for comparison of those strategies within the bourndaries of the trial population and interventions/endpoints tested. Notably although LDL is first for me as well, subjects in the study were at a virtual maximum of simvastatin or atorvastatin. Although a second line target, HDL is a topic of some focus within ATP3. Will be interesting to see if ATP 4 identifies a basis to extend their prior recommendations.
Competing interests pertaining specifically to this post, comment, or both:
I have received honoraria (lecture fees) from Abbott- which are donated to charity.
Am I missing something?
Adding niacin to LDL lowering medications dramatically improved the hard endpoint of myocardial infarction in the HATS and FATS trials. Just because the DATA is old does not mean it is not valid. LDL lowering has severe limits with an aggregate improvement of about 30% reduction in MI incidence. Improving on LDL lowering outcomes is critical. Adding extended release nicotinic acid is a necessity in many cases. Arbiter-6 HALTS gives us another reason to be doing this. In my practice, I have found that subjects taking niacin have a dramatic reduction in plaque progression by EBT calcium imaging compared to subjects taking statins alone. Stability of calcified plaque by EBT imaging is the surrogate that most strongly correlates with reduction in MIs, I have found the calcified plaque stability with the use of niacin to be independent of baseline HDL level.
Competing interests pertaining specifically to this post, comment, or both:
I enjoy preventing heart attacks. I have a financial interest in a facility that can do EBT heart scans and carotid ultrasounds. I have received consulting fees from Pfizer, GSK, and Abbott labs.