American Heart Association Late Breaking Clinical Trial Report: In Patients on Statins, Raising Good Cholesterol with Niacin, but not Reducing Bad Cholesterol with Ezetimibe, Decreases Plaque Build-Up

American Heart Association Late Breaking Clinical Trial Report: In Patients on
Statins, Raising Good Cholesterol with Niacin, but not Reducing Bad
Cholesterol with Ezetimibe, Decreases Plaque Build-Up

Study highlights:

In patients with or at high-risk for coronary artery disease and LDL (bad
cholesterol) treated with statins to < 100mg/dL but low HDL (good
cholesterol), adding medication to raise HDL was compared with lowering LDL
further.

Patients were randomized to the addition of niacin (primarily to raise HDL),
or ezetimibe (to further lower LDL cholesterol). Plaque buildup in the lining
of the neck arteries was significantly reduced only in the niacin group.

DUE TO AN EMBARGO BREAK, THE EMBARGO ON THIS STUDY IS RELEASED

ORLANDO, Fla., Nov. 15 /PRNewswire-USNewswire/ -- In combination with statins,
adding a medication that raises high-density lipoprotein (HDL) cholesterol was
more effective in reversing artery wall plaque buildup and in reducing heart
disease risk than adding a drug that lowers low-density lipoprotein (LDL)
cholesterol, researchers reported today at the American Heart Association
Scientific Sessions 2009.

In the study titled The Effect of Extended-release Niacin or Ezetimibe Added
to Chronic Statin Therapy On Carotid Intima Media Thickness(ARBITER 6-HALTS),
researchers found:

-- Adding the cholesterol drug niacin to a statin improved HDL ("good")
cholesterol levels and significantly reduced arterial plaque buildup
within 8 months, with further improvement seen at the end of the study
(14 months).

-- A second approach, adding ezetimibe to a statin, lowered LDL ("bad")
cholesterol to a greater extent, but did not raise HDL. With it,
there
was no overall effect on arterial build up in the neck arteries.

-- With ezetimibe, greater reductions in LDL cholesterol paradoxically
were
associated with more arterial buildup, a result opposite to that
expected.

-- The incidence of major cardiovascular events such as fatal and
non-fatal
heart attack was higher in the ezetimibe group as compared to the
niacin
group (5 percent vs. 1 percent).

HDL And LDL Treatment Strategies (HALTS) was a prospective, randomized,
parallel group, open-label, blinded endpoint study conducted at Walter Reed
Army Medical Center in Washington, D.C., and Washington Adventist Hospital in
Tacoma Park, Md. It included 363 adults (80 percent male, average age 68
years) with or at high risk for atherosclerotic cardiovascular disease.

All participants were on cholesterol-lowering statin drugs, and their LDL
cholesterol was at the treatment goal of under 100 milligrams per deciliter
(mg/dL) of blood. Their HDL cholesterol was lower than 50 mg/dL for men and
55 mg/dL for women.

The researchers randomly assigned the subjects to receive either niacin or
ezetimibe in addition to their usual statin. The primary endpoint was the
change in the wall thickness of the carotid artery in the neck between the two
groups of patients. In June, researchers halted the trial early because the
primary endpoint was met. Specifically, 14-month follow-up data on 208
patients showed that in the niacin group, average HDL cholesterol rose from 42
mg/dL to 50 mg/dL and there was a significant regression in artery wall
thickness. In the ezetimibe group, average LDL cholesterol levels dropped
from 83 mg/dL to 66 mg/dL; however no overall change was found in average
artery wall thickness.

LDL cholesterol is generally linked to the buildup of plaque in the arteries,
which makes them more likely to become narrowed, and can lead to heart attack
or stroke. HDL cholesterol helps clear LDL cholesterol from the blood in a
process called reverse cholesterol transport.

"These findings for ezetimibe are counter to the prevailing understanding of
LDL cholesterol -- that lowering LDL cholesterol results in slowing of the
atherosclerotic process as has been convincingly shown for other classes of
lipid modifying drugs, such as statins and bile acid resins," said Allen J.
Taylor, M.D. FAHA, principal investigator of the study and director of
Advanced Cardiovascular Imaging and the Lipid/Prevention Clinic in the
Department of Medicine (Cardiology) at Washington Hospital Center in
Washington, D.C.

In earlier studies demonstrating the protective effects of statins,
researchers found strong associations between LDL cholesterol reduction and
the prevention of cardiovascular disease. Consequently, many people now view
LDL cholesterol reduction as a way to measure whether a treatment will be
useful.

But HALTS researchers' findings "challenge the use of LDL reduction as a
guaranteed surrogate for clinical performance, particularly for new clinical
compounds, and in this particular case, ezetimibe," Taylor said. Patients
should know their HDL numbers and, if they are low, ask their doctors if
adding a treatment such as niacin is right for them once their LDL is treated
to goal with a statin drug, he said.

Co-authors are: Todd C. Villines, M.D.; Patrick J. Devine, M.D.; Mark Turco,
M.D.; Len Griffen, M.D.; Michael Miller, M.D.; Eric J Stanek, Pharm. D.; and
Neil J Weissman, M.D.

Study sponsor: Abbott Inc. (initially Kos Pharmaceuticals, Inc., Cranbury,
N.J.) provided an unrestricted, investigator-initiated research grant
administered by the Henry M. Jackson Foundation for the Advancement of
Military Medicine in Rockville, Md. The investigators were solely responsible
for all aspects of the study and the final decisions on manuscript content.

Disclosures: Dr. Taylor reports receiving lecture fees from Abbott. Dr. Turco
reports receiving consulting and lecture fees from Abbott Cardiovascular. Dr.
Miller reports receiving lecture fees and grant support from Merck-Schering
Plough. Dr. Villines reports receiving lecture fees from Novartis
Pharmaceuticals. Dr. Devine reports receiving consulting fees from Medacorp,
MDLinx, and Guidpoint Global, equity ownership in Evergreen solar, Openwave,
Unifi, Novavax, Genaera Pharm, and Generex Biotech. Dr. Stanek is senior
director of research in Personalized Medicine Research and Development at
Medco Health Solutions, Inc. (Franklin Lakes, N.J.), but all work performed on
this trial was independent of this relationship. No other potential conflict
of interest was reported.

Statements and conclusions of study authors that are presented at American
Heart Association scientific meetings are solely those of the study authors
and do not necessarily reflect association policy or position. The
association makes no representation or warranty as to their accuracy or
reliability. The association receives funding primarily from individuals;
foundations and corporations (including pharmaceutical, device manufacturers
and other companies) also make donations and fund specific association
programs and events. The association has strict policies to prevent these
relationships from influencing the science content. Revenues from
pharmaceutical and device corporations are available at
www.americanheart.org/corporatefunding.

NR09 - 1164 (SS09/ARBITER 6-HALTS Taylor)

SOURCE American Heart Association

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