Thursday, November 17, 2011

AIM-HIGH Hits Low & Misses Target Part 2

6 months ago, I noted that the NHLBI had prematurely brought a halt to the AIM-HIGH study which sought to demonstrate the benefit of high dose extended-release niacin in addition to intensive lipid lowering w/high dose simvastatin +/- ezetimibe.  Unfortunately, the study did not turn out as expected, such that, despite a statistically significant increase in HDL, there was no decrease in cardiac events.  However, we were all left to speculate since the only available information at that time was from a press release.

Well, just 2 days ago, the results of AIM-HIGH were release early online by the NEJM.  In this randomized, double-blind, placebo-controlled trial, the participants were given either 2,000mg/d of extended release niacin, eg Niaspan, or a matching placebo, in addition to high dose simvastatin 40-80mg/d +/- ezetimibe 10mg/d to achieve an LDL <80mg/dL in patients w/known coronary artery disease.  After 3 years, there was no difference in cardiac event rates despite niacin increasing HDL from 35mg/dL up to 42mg/dL, dropping TG from 164mg/dL down to 122mg/dL and LDL from 74mg/dL down to 62mg/dL.

So is this the end for extended-release niacin?  The editorialist would argue differently.  Certainly, there is no evidence to support the use of niacin in someone w/known heart disease.  But perhaps niacin might provide benefit in statin-intolerant patients?  And let's not forget that we're still waiting on the larger HPS2-THRIVE study due out in 2013.  However, I would argue for two other alternative theories.  

First, perhaps we didn't raise HDL adequately.  Sure, 42mg/dL is into the "normal" reference range (40-60mg/dL) but it only cleared the lower limit of normal by 2mg/dL.  Observationally, it's not until patients have HDL >60mg/dL that we notice a decrease in group event rates.  But as I mentioned yesterday, this is akin to tutoring someone from an F grade (35mg/dL) to D- grade (42mg/dL) but not bothering to push into the A range (>60mg/dL).  

Second, while I agree that niacin no longer has a role in secondary prevention, that says nothing of a possible role in primary prevention.  Which brings to mind the American Academy of Pediatrics' recent recommendation to screen for dyslipidemia in children as young as 9-11yo.  Controversial?  Sure!  But the idea is not so much to start our kids on a lifetime of statins but rather to look at heart disease as a lifelong condition that requires decades to manifest and thus could conceivably be delayed/improved if lifestyle changes were given adequate time to take effect.  Something to consider while we wait for HPS2-THRIVE.

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