TUESDAY, Nov. 9 (HealthDay News) -- Using high doses of
cholesterol-lowering drugs called statins appears to reduce the
risk of heart attack, stroke or the need for additional cardiac
procedures more than regular doses of statins in people who have
had a stroke or suffer from heart disease, two new studies
This benefit was seen even among those whose cholesterol levels
were already low, researchers say. Statins include widely used
medications such as Crestor, Lipitor and Zocor.
"For high-risk people, those with heart disease or [who] have had a stroke who are taking a standard dose of a statin, further reduction in LDL cholesterol will give them extra benefit," said Dr. Colin Baigent of the Clinical Trial Service Unit and Epidemiological Studies Unit at University of Oxford in the United Kingdom, who was involved in both studies. This applied even if the patients already had low levels of low-density lipoprotein (LDL, or "bad") cholesterol, he noted.
The reports are published in the Nov. 9 online edition of
In the first study, researchers at Oxford and the University of
Sydney in Australia collected data from studies on 170,000 patients
who took part in 26 trials. This type of review, called a
meta-analysis, gathers data from various studies to see if a
Among these trials, five compared high doses of statins with
regular doses and the other 21 studies compared people taking
statins with people not taking the drugs.
The researchers found that in trials comparing statin doses,
taking high-dose statins reduced the odds of having a stroke by an
additional 15 percent, compared to the usual doses of statins.
Specifically, there was a 13 percent reduction in heart-related
death or heart attack, a 19 percent reduction in the need for a new
heart operation and a 16 percent reduction in stroke, the
When they did an updated analysis of the 21 trials, first major
cardiovascular events (such as heart attack and stroke) were
lowered by a "highly significant" 22 percent for a 1.07 millimole
per liter (mmol/L) reduction of LDL cholesterol.
Taking all 26 trials together, deaths were reduced by 10 percent
for 1 mmol/L in reduction of LDL cholesterol, with no significant
effect on deaths from stroke or other vascular causes.
In addition, there were no significant effects of statins on
deaths due to cancer or other non-vascular causes, and no excess
risk of cancer, even at low LDL cholesterol concentrations.
The second study is a randomized trial called the Study of the
Effectiveness of Additional Reductions in Cholesterol and
Homocysteine (SEARCH), led by professor Jane Armitage, also a
scientist at the CTSU in Oxford.
This trial looked at the benefits of statin therapy with 80
milligrams (mg) versus 20 mg simvastatin (Zocor) among 12,000 heart
The study was supported by a grant from Merck (manufacturer of
Over almost seven years of follow-up, those taking the higher
dose statin had greater reductions in LDL cholesterol compared with
those taking the lower dose.
The reduction in LDL cholesterol from the higher dose ended up
decreasing the risk of a major cardiac event by 6 percent, the
researchers found, although the statistic in itself was not
The researchers noted that the higher dose of Zocor
(simvastatin) did result in a risk of a muscle disease 10 times
higher than that associated with the lower dose. The muscle
disease, known as myopathy, can cause pain, weakness, and in its
rare but most severe form, destruction of the muscle tissue leading
to kidney failure. Researchers found that two cases of myopathy
occurred with the low dose and 53 cases with the higher dose.
Researchers also found that rhabdomyolysis -- the most severe
form of the muscle disease associated with statins -- was diagnosed
in seven participants given 80 mg of Zocor (simvastatin), compared
to none who were given 20 mg of simvastatin. Two died within a few
weeks of developing the disorder, with one cause of death
mentioning the muscle disorder as a contributing factor.
Researchers also found that seven participants had creatine
kinase levels higher than 40 times the upper limit of normal -- a
possible indicator of kidney damage. For this reason, they noted
that the incidence of severe muscle disease on 80 mg of Zocor might
be an "underestimate."
Baigent noted this side effect is one associated with Zocor, but
taking lower doses of other, more powerful statins may alleviate
the problem. "There are newer ways of increasing LDL cholesterol
reduction by using the newer, more potent statins such a Lipitor or
Crestor," he said. (All statins carry the risk of myopathy, but
lower dosages are associated with a reduced risk.)
Bernard M.Y. Cheung, from the University of Hong Kong and
coauthor of an accompanying journal editorial, said that "people
who are at risk from heart attacks and strokes should have their
LDL-cholesterol lowered intensively."
Their doctors should consider prescribing a statin, either at a
high dose or using a more powerful statin, he said.
"If you are at risk from a heart attack or stroke, either because you have had these conditions before or because you have the risk factors for them, you should be considered for intensive treatment to lower the LDL cholesterol," Cheung said.
"If your blood cholesterol is raised but you do not have other risk factors for heart disease and stroke, then your doctor may well decide that you do not need to take any drugs to lower cholesterol," he said. "But if you are at risk from those diseases, you would need intensive treatment to lower LDL cholesterol, even if your LDL cholesterol level is not very high," he added.
Commenting on the studies, Dr. Gregg Fonarow, American Heart
Association spokesman and professor of cardiology at the University
of California, Los Angeles, said that "despite the proven benefits
of LDL cholesterol-lowering with statin therapy, many physicians
have been reluctant to prescribe and patients reluctant to take
higher doses of more potent statin medications due to concerns
about side effects or safety."
Lowering LDL cholesterol by 50 to 60 percent with potent statins
such as atorvastatin at 80 mg or rosuvastatin at 20 to 40 mg lowers
the risk of major cardiovascular events by 50 to 60 percent, he
"Most patients tolerate higher doses of more potent statins equally well as lower doses of less potent statins," Fonarow said. "Millions of patients with or at high risk of cardiovascular disease, who would derive additional cardiovascular protection from higher doses of more potent statins, are not currently treated with these agents. But [they] should be."
For more information on statins, visit the
U.S. National Library of Medicine.
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