Media Reports May Have Distorted Risk of Niacin in
Halt of Clinical Trial
Government agencies advise seniors to not stop
taking niacin until they have talked to their doctor
By Tucker Sutherland, editor, SeniorJournal.com
June 1, 2011 – Many senior citizens are concerned
and confused by news reports about the decision of the National Heart,
Lung, and Blood Institute (NHLBI) to halt a clinical trial involving
niacin (vitamin B3). An impression left by many media reports was that
this vitamin may be dangerous, because one of the reasons the trial was
halted was “a small and unexplained increase in ischemic stroke rates”
among those taking the niacin. What too many reports failed to emphasize
was the “significant” risk of a cardiovascular event to those in the
test group and that this was a very high dose of niacin, in addition to a
statin drug.
As the news release about the NHLBI action said,
“Niacin, also known as Vitamin B3, has long been known to raise HDL and
lower triglycerides.” This is why doctors frequently recommend it to
many senior citizens.
But many media reports indicated niacin alone was
the villain. The headline by U.S. News and World Report said, for
example, "Trial Stopped After Niacin Brings No Benefit to Heart
Patients." ShortNews.com said, "Niacin Trial Too Risky to Go On."
Medical News Today's headline said, "Niacin Does Not Reduce
Stroke of Heart Attack Risk..."
Those in this trial were given a “high dose,
extended-release niacin (brand name, Niaspan) in gradually increasing
doses up to 2,000 mg per day.”
This trial, however, involved a very special group,
more than half had already experienced a heart attack. About half were
senior citizens – age 65 or older.
After the trial was stopped, the Food and Drug
Administration issued a statement, which included the following:
“Nine of the ischemic strokes in the simvastatin
plus extended-release niacin group occurred in participants who had
stopped taking their niacin for at least 2 months and up to 4 years
before their stroke. Therefore, it is unclear what role, if any, niacin
contributed to this imbalance in ischemic stroke.
“At this time, FDA has made no new conclusions
or recommendations regarding the use of extended-release niacin alone or
in combination with simvastatin or other statins. The Agency will
conduct a comprehensive review of the AIM-HIGH trial data as soon as
they become available to determine their impact on the approved
indications for extended-release niacin.
“High-dose niacin is a prescription drug that is
used along with diet and exercise to manage cholesterol and fat
(triglyceride) levels in the blood. It is also indicated as a
monotherapy to lower the risk of heart attacks in patients who have had
a heart attack and have high cholesterol. High-dose niacin is available
as an extended-release tablet under the brand-name Niaspan, and is also
available in combination with simvastatin under the brand-name Simcor,
and in combination with lovastatin under the brand-name Advicor.
“Healthcare professionals should consider the
available clinical information on high-dose extended-release niacin and
statin drugs when deciding what cholesterol-lowering medication to
prescribe.
“Patients should not stop taking their current
medications without talking to their healthcare professional.”
The news release by the NHLBI points out that
several other trials testing the same topic as this trial - the impact
of raising HDL on the risk of cardiovascular events while maintaining
excellent LDL control - including a large international trial of high
dose, extended-release niacin, are still ongoing.
Below is the complete news release by the NLBI,
which gives a more balanced report that has been too frequently
reported.
NIH stops
clinical trial on combination cholesterol treatment
Lack of
efficacy in reducing cardiovascular events prompts decision
Niacin is used with diet changes
(restriction of cholesterol and fat intake) to reduce the amount of
cholesterol and certain fatty substances in your blood. Niacin is also
used to prevent and treat pellagra (niacin deficiency), a disease caused
by inadequate diet and other medical problems. Niacin is a B-complex
vitamin.
How should this medicine be used?
Niacin comes as a tablet and an
extended-release (long-acting) tablet to take by mouth. The regular
tablet usually is taken two to three times a day with meals, and the
extended-release tablet is taken once a day, at bedtime, with food.
Follow the directions on your prescription label or package label
carefully, and ask your doctor or pharmacist to explain any part you do
not understand. Take niacin exactly as directed. Do not take more or
less of it or take it more often than prescribed by your doctor.
Swallow the extended-release
tablets whole; do not split, chew, or crush them.
Your doctor will probably start you
on a low dose of niacin and gradually increase your dose.
Continue to take niacin even if you
feel well. Do not stop taking niacin without talking to your doctor.
Other uses for this medicine
This medication is sometimes
prescribed for other uses; ask your doctor or pharmacist for more
information.
The National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health has stopped a clinical trial studying a blood lipid treatment 18
months earlier than planned. The trial found that adding high dose,
extended-release niacin to statin treatment in people with heart and
vascular disease, did not reduce the risk of cardiovascular events,
including heart attacks and stroke.
Participants were
selected for AIM-HIGH because they were at risk for cardiovascular
events despite well-controlled low-density lipoprotein (LDL or bad
cholesterol). Their increased risk was due to a history of
cardiovascular disease and a combination of low high-density lipoprotein
(HDL or good cholesterol) and high triglycerides, another form of fat in
the blood. Low HDL and elevated triglycerides are associated with an
increased risk of cardiovascular events.
While lowering LDL decreases
the risk of cardiovascular events, it has not been shown that raising
HDL similarly reduces the risk of cardiovascular events.
During the study’s
32 months of follow-up, participants who took high dose,
extended-release niacin and statin treatment had increased HDL
cholesterol and lowered triglyceride levels compared to participants who
took a statin alone. However, the combination treatment did not reduce
fatal or non-fatal heart attacks, strokes, hospitalizations for acute
coronary syndrome, or revascularization procedures to improve blood flow
in the arteries of the heart and brain.
"Seeking new and
improved ways to manage cholesterol levels is vital in the battle
against cardiovascular disease," said Susan B. Shurin, M.D., acting
director of the NHLBI.
"This study sought
to confirm earlier and smaller studies. Although we did not see the
expected clinical benefit, we have answered an important scientific
question about treatment for cardiovascular disease. We thank the
research volunteers whose participation is key in advancing our
knowledge in this critical public health area, and the dedicated
investigators who conducted the study."
The AIM-HIGH
trial, which stands for Atherothrombosis Intervention in Metabolic
Syndrome with Low HDL/High Triglycerides: Impact on Global Health,
enrolled 3,414 participants in the United States and Canada with a
history of cardiovascular disease who were taking a statin drug to keep
their LDL cholesterol low.
Study participants
also had low HDL cholesterol and high triglycerides, which meant that
they were at significant risk of experiencing future cardiovascular
events.
Niacin, also known
as Vitamin B3, has long been known to raise HDL and lower triglycerides.
Eligible
participants were randomly assigned to either high dose,
extended-release niacin (Niaspan) in gradually increasing doses up to
2,000 mg per day (1,718 people) or a placebo treatment (1,696 people).
All participants
were prescribed simvastatin (Zocor), and 515 participants were given a
second LDL cholesterol-lowering drug, ezetimibe (Zetia), in order to
maintain LDL cholesterol levels at the target range between 40-80 mg/dL.
The NHLBI funded
the AIM-HIGH study with additional support from Abbott Laboratories, a
pharmaceutical company based in Abbott Park, Ill. Abbott also provided
Niaspan and Merck Pharmaceuticals, based in Whitehouse Station, N.J.,
provided Zocor. All drugs used in the study were approved for marketing
in the United States and Canada and have been on the market for many
years.
Researchers began
recruiting participants in early 2006. The study was scheduled to finish
in 2012.
The average age of
the participants was 64 years.
Pre-existing
medical conditions included –
● coronary artery disease (92 percent);
● metabolic syndrome, which is a cluster of risk factors for heart
disease (81 percent);
● high blood pressure (71 percent); and
● diabetes (34 percent).
More than half of
participants reported having a heart attack prior to entering the study.
The rationale for
the AIM-HIGH study was based in part on a large number of observational
studies that consistently showed that low HDL cholesterol increases the
risk of cardiovascular events in men and women, independent of high LDL
cholesterol. In addition, previous small clinical studies showed that
relatively high residual cardiovascular risk exists among patients with
cardiovascular disease, low HDL cholesterol, and high triglycerides
despite intensive management of LDL cholesterol.
However, efforts
to find HDL-raising treatments that actually reduce this residual risk
have thus far proved disappointing. Fenofibrate, an HDL-raising drug,
failed to reduce the rate of cardiovascular events in patients with
diabetes in the Action to Control Cardiovascular Risk in Diabetes
(ACCORD trial) despite favorable effects on HDL and triglycerides.
Another HDL-raising drug, torcetrapib, actually increased the rate of
cardiovascular events in the Investigation of Lipid Level Management to
Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial
despite lowering LDL and triglycerides and raising HDL levels, as
intended.
Earlier studies of
niacin had shown more favorable results. Unlike AIM-HIGH, the earlier
studies were not designed specifically to evaluate the impact of raising
HDL on the risk of cardiovascular events while maintaining excellent LDL
control.
Several other
trials testing this hypothesis, including a large international trial of
high dose, extended-release niacin, are still ongoing.
As is customary in
clinical trials, the NHLBI established an independent data and safety
monitoring board (DSMB) to monitor trial progress and participant
safety. At a regularly scheduled meeting on April 25, 2011, the study's
DSMB concluded that high dose, extended-release niacin offered no
benefits beyond statin therapy alone in reducing cardiovascular-related
complications in this trial.
The rate of
clinical events was the same in both treatment groups, and there was no
evidence that this would change by continuing the trial. For this
reason, the DSMB recommended that the NHLBI end the study.
The DSMB also
noted a small and unexplained increase in ischemic stroke rates in the
high dose, extended-release niacin group. This contributed to the NHLBI
acting director's decision to stop the trial before its planned
conclusion.
During the
32-month follow-up period, there were 28 strokes (1.6 percent) reported
during the trial among participants taking high dose, extended-release
niacin versus 12 strokes (0.7 percent) reported in the control group.
Nine of the 28 strokes in the niacin group occurred in participants who
had discontinued the drug at least two months and up to four years
before their stroke.
Previous studies
do not suggest that stroke is a potential complication of niacin, and it
remains unclear whether this trend in AIM-HIGH arose by chance, was
related to niacin administration or some other issue.
All AIM-HIGH study
participants have been informed of the results and will be scheduled for
clinic visits within the next 2.5 months. Participants will be followed
for an additional 12 to 18 months.
"Patients who were
not in the AIM-HIGH trial should not stop taking high dose,
extended-release niacin without talking to their doctor first," said
Shurin.
"The lack of
effect on cardiovascular events is unexpected and a striking contrast to
the results of previous trials and observational studies," said Jeffrey
Probstfield, M.D., AIM-HIGH co-principal investigator and professor of
medicine and epidemiology at the University of Washington, Seattle. "The
AIM-HIGH findings do not support the trial's hypothesis that, in the
population studied, adding extended-release niacin to simvastatin in
participants with well-controlled LDL cholesterol can provide additional
clinical benefit."
"The results from
AIM-HIGH should not be extrapolated to apply to potentially higher-risk
patients such as those with acute heart attack or acute coronary
syndromes, or in patients whose LDL cholesterol is not as
well-controlled as those in AIM-HIGH," said William E. Boden, M.D.,
AIM-HIGH co-principal investigator and professor of medicine and
preventive medicine at the University at Buffalo, N.Y.
The niacin tested
in the study is a proprietary formulation used in doses of 500-2,000
milligrams (mg), manufactured by Abbott Laboratories and approved and
regulated by the U.S. Food and Drug Administration.
Low doses of
niacin, typically 20 to 100 mg, can be found in multivitamin
formulations available without a prescription.
The FDA regulates
the use of high doses of niacin (over 500 mg), which is approved by
prescription for helping treat low HDL cholesterol and/or high
triglycerides. At prescription-level doses, some people experience
flushing. The extended-release formulation of niacin tested in AIM-HIGH
was intended to help reduce the likelihood of flushing.
An estimated 1 in
7 Americans has high blood cholesterol. It is a major risk factor for
cardiovascular disease, which kills 800,000 Americans a year.
Cholesterol can build up in the walls of arteries and cause them to
narrow, a condition known as atherosclerosis.
“As we continue to
search for new approaches to treating cholesterol problems, it is
important to remember the value of existing treatments. The key to
treating high cholesterol so patients can reduce their risk of
cardiovascular disease is to lower the level of LDL cholesterol, through
well-established drug treatments such as statins and lifestyle changes,”
said Patrice Desvigne-Nickens, M.D., NHLBI project officer for the
AIM-HIGH trial.
The AIM-HIGH
investigators will now focus on completing data collection and analysis.
The preliminary outcomes of the study are expected to be reported at
scientific meetings in the fall of 2011.
Part of the
National Institutes of Health, the National Heart, Lung, and Blood
Institute (NHLBI) plans, conducts, and supports research related to the
causes, prevention, diagnosis, and treatment of heart, blood vessel,
lung, and blood diseases; and sleep disorders. The Institute also
administers national health education campaigns on women and heart
disease, healthy weight for children, and other topics. NHLBI press
releases and other materials are available online at
www.nhlbi.nih.gov.
About the
National Institutes of Health (NIH): NIH, the nation's medical research
agency, includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. NIH is the primary federal
agency conducting and supporting basic, clinical, and translational
medical research, and is investigating the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and
its programs, visit
www.nih.gov.
June 1, 2011 – Many senior citizens are concerned
and confused by news reports about the decision of the National Heart,
Lung, and Blood Institute (NHLBI) to halt a clinical trial involving
niacin (vitamin B3). An impression left by many media reports was that
this vitamin may be dangerous, because one of the reasons the trial was
halted was “a small and unexplained increase in ischemic stroke rates”
among those taking the niacin. What too many reports failed to emphasize
was the “significant” risk of a cardiovascular event to those in the
test group and that this was a very high dose of niacin, in addition to a
statin drug.