I was in the earlier trial - (AIM-HIGH) study - that just had the niacin, no flushing blocker, I quit the trial I was in because of the exacerbation of existing excema I had on my leg. I was scratching at it until it bled.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=128784&CultureCode=en
The
largest randomised study of the vitamin niacin in patients with
occlusive arterial disease (narrowing of the arteries) has shown a
significant increase in adverse side-effects when it is combined with
statin treatment.
Results from the HPS2-THRIVE study (Heart Protection Study 2 –
Treatment of HDL to Reduce the Incidence of Vascular Events), including
the reasons patients stopped the study treatment, are published online
today (Wednesday) in the European Heart Journal [1].
Niacin has been used for decades to help increase levels of “good”
HDL cholesterol and to decrease levels of “bad” LDL cholesterol and
triglycerides (fats) in the blood in people at risk of cardiovascular
problems such as heart disease and stroke. However, it has a number of
side-effects including flushing of the skin. Another drug, laropiprant,
can reduce the incidence of flushing by blocking the prostaglandin D2
receptor that is involved in the process. Therefore, the HPS2-THRIVE
study investigated whether combining extended-release niacin with
laropiprant (ERN/LRPT), given in addition to an LDL cholesterol-lowering
statin, simvastatin, could reduce the risk of cardiovascular problems
in people at high risk due to existing occlusive arterial disease.
A total of 25,673 patients from China, the UK and Scandinavia were
randomised between April 2007 and July 2010 to receive either 2g of
extended release niacin plus 40 mg of laropiprant or matching placebo.
In addition, all participants received intensive LDL
cholesterol-lowering therapy with simvastatin (with or without
ezetimibe). Researchers from the Clinical Trial Service Unit &
Epidemiological Studies Unit (CTSU) at the University of Oxford (UK),
who were responsible for designing and conducting the trial and
analysing the results, followed the patients for an average of 3.9
years.
By the end of the study, 25% of patients taking ERN/LRPT had stopped
their treatment, compared with 17% of patients taking placebo.
Jane Armitage, Professor of Clinical Trials and Epidemiology &
Honorary Consultant in Public Health Medicine at the CTSU, said: “The
main reason for patients stopping the treatment was because of adverse
side-effects, such as itching, rashes, flushing, indigestion, diarrhoea,
diabetes and muscle problems. We found that patients allocated to the
experimental treatment were four times more likely to stop for
skin-related reasons, and twice as likely to stop because of
gastrointestinal problems or diabetes-related problems.
“We found that, in the trial as a whole, participants in the
experimental arm had a more than four-fold increased risk of myopathy
(muscle pain or weakness with evidence of muscle damage) compared with
the placebo group. This is highly significant. It appeared that this
effect was about three times greater among participants in China than
those in Europe, for reasons that are not clear. In the placebo arm
(i.e. those on statin-based treatment alone), the statin-related
myopathy was more common among participants in China than those in
Europe. Therefore – in combination with the greater effect of ERN/LRPT
on myopathy in China – the excess number of cases of myopathy caused by
ERN/LRPT (though low in both regions) was over ten times greater among
participants in China than those in Europe (0.53 percent per year
compared to 0.03 percent per year).”
Dr Richard Haynes, Clinical Coordinator at the CTSU, said: “This is
the largest randomised trial of extended release niacin treatment and it
provides uniquely reliable results on adverse side-effects and the
ability of patients to tolerate them. Although 25 percent of patients
stopped the treatment early, 75 percent continued on it for
approximately four years. Currently, we are analysing the final data on
the cardiovascular outcomes from the trial, and once we have these we
will know whether or not the benefits of the treatment outweigh the
myopathy, skin and gastrointestinal problems.”
The researchers will be presenting full results on the cardiovascular
outcomes at the annual meeting of the American College of Cardiology in
March and these will be published in another paper afterwards [2].
The co-principal investigator of the study, Dr Martin Landray, Reader
in Epidemiology and Honorary Consultant Physician at the CTSU, said:
“Previous research had suggested that improving cholesterol levels in
high-risk patients might translate into a 10-15 percent reduction in
major vascular events such as heart attacks and strokes. In the
HPS2-THRIVE study, 3,400 of the 25,673 participants suffered a major
vascular event over an average of four years of follow-up. This means
the study has excellent statistical power to discover the effectiveness
or otherwise of the treatment.”
In an accompanying editorial [3], Professor Ulf Landmesser, of the
University Hospital Zurich (Switzerland), points out that although the
study showed an increase in myopathy, it also showed that the ERN/LRPT
substantially lowered LDL cholesterol and triglycerides by nearly 20%.
He writes that these observations “raise important questions as to why
niacin/laropiprant did not reduce major cardiovascular events”, and he
wonders whether laropiprant “is really biologically inert with respect
to atherosclerosis and thrombosis”.
He concludes that “niacin has failed as a valuable ‘partner’ of
statin therapy in lipid-targeted approaches to further reduce major
cardiovascular events in high-risk patients”. He continues: “At present,
statin therapy has been clearly shown to reduce vascular events
effectively and is reasonable well tolerated in most patients. We will
still have to wait for the results of … ongoing studies to see whether
another lipid-targeted intervention can further reduce vascular events
in addition to statin therapy.”
Notes:
[1] “HPS2-THRIVE randomized placebo-controlled trial in 25 673
high-risk patients of ER niacin/laropiprant: trial design, pre-specified
muscle, and liver outcomes and reasons for stopping study treatment”,
by Richard Haynes, Lixin Jiang, Jemma C. Hopewell, Jing Li, Fang Chen,
Sarah Parish, Martin J. Landray, Rory Collins, and Jane Armitage, The
HPS2-THRIVE Collaborative Group. European Heart Journal.
doi:10.1093/eurheartj/eht055
[2] In December 2012 the pharmaceutical company Merck, which
manufactures ERN/LRPT under the trade name Tredaptive and which funded
the HSP2-THRIVE study, issued a statement saying the trial had failed to
meet its primary endpoint and that “the combination of extended-release
niacin and laropiprant to statin therapy did not significantly further
reduce the risk of the combination of coronary deaths, non-fatal heart
attacks, strokes or revascularizations compared to statin therapy.”
ERN/LRPT is not approved for use in the USA, and on January 11, Merck
announced that it was “taking steps to suspend the availability of
TREDAPTIVE™ (extended-release niacin/laropiprant) tablets worldwide.”
[3] ”The difficult search for a ‘partner’ of statins in
lipid-targeted prevention of vascular events: the re-emergence and fall
of niacin”, by Ulf Landmesser. European Heart Journal.
doi:10.1093/eurheartj/eht064
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