CLINICAL
NEWS
American College of Cardiology Extended Learning
ACCEL interviews and topical summaries of cardiology’s
most interesting research areas
Niacin, Fibrates, and the Highly ‘Difficult’ Lipoprotein
Is add-on therapy on its way out?
F
rom the beginning, it just sounded too good
to be a true: a vitamin that reduced “bad cholesterol” while simultaneously raising – often
dramatically – the level of “good cholesterol.” Indeed,
when niacin was first popularized in the late 1980s,
criticism from the medical community was harsh.
As papers began to be presented at major meetings,
the discussions generally devolved to something
dangerously close to playground name-calling.
Part of the problem: niacin was first popularized in the general press and, only then, did the
data back-fill begin to establish clinically what the
public already believed. Over time, the data did
indeed establish the effectiveness of niacin; as long
as the irritating flush was acceptable, it performed
as promised.
At the same time niacin was being promoted as
“a cholesterol cure,” the first statin (lovastatin) was
approved by the US Food and Drug Administration
(FDA). For most people, statins proved easier to
tolerate than high-dose niacin, producing comparable (and eventually superior) LDL-C lowering than
niacin. Given the residual risk of patients on statin
therapy, niacin became a second-line agent.
Early trials evaluating the combination of statin
and niacin therapy enrolled a relatively modest
number of patients over a relatively short treatment
period. Therefore, a randomized clinical trial (RCT)
powered for clinical endpoints was required to
determine whether combined niacin/statin therapy
was more effective than statin monotherapy alone.
NIACIN FALLS SHORT IN AIM-HIGH
AIM-HIGH (the Atherothrombosis Intervention in
Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes trial)
compared therapy with niacin/simvastatin to simvastatin alone, but failed to demonstrate an incremental
benefit of niacin among patients with ASCVD and
on-treatment LDL-C values < 70 mg/dl.1
More than a failure of niacin, the results suggested a general failure of the HDL-C hypothesis. Soon
thereafter, Michos and colleagues (including Roger
S. Blumenthal, MD) reviewed the epidemiologic
evidence s \ ܝ[