"How Common Are Muscle Side Effects from Statins?"
There is now overwhelming evidence to support reducing LDL cholesterol—
bad cholesterol—to reduce atherosclerotic cardiovascular disease
the number one killer of men and women.
So why is adherence to cholesterol- lowering statin drug therapy
such a major challenge? The majority of studies reported at least 40%,
and as much as 80%, of patients did not comply fully with
statin treatment recommendations. Three-quarters may flat out
stop taking them, or sometimes up to nearly 90% discontinue treatment.
When asked why, most former statin users, or discontinuers, cited muscle pain,
a side effect, as the primary reason for stopping the pills.
By far the most prevalent and important adverse events, up to 72%
of all statin side effects are statin- associated muscle symptoms.
Taking Coenzyme Q10 supplements as a treatment for statin-associated muscle
symptoms was a good idea in theory, but they don't actually appear to help.
Normally, side-effect symptoms go away when you stop the drug,
but sometimes can linger a year or more. There's evidently growing evidence
that statin intolerance is predominantly psychosocial, not pharmacological,
meaning—wait—meaning maybe it's mostly just in people's heads?
"Statins have developed a bad reputation with the public," one editorial read,
"a phenomenon driven largely by proliferation on the Internet of
bizarre and unscientific... criticisms of these drugs."
Maybe it's Google that leads to statin intolerance? But come on,
people have been going off statins for decades
before there even was an Internet.
What kind of data has doctors suggesting that patients are falsely misattributing
normal aches and pains to be statin side effects? Well, if you take people
who claim to have statin-related muscle pain and randomize them back and forth
between statins and an identical-looking placebo in three-week blocks,
they can't actually tell whether they're getting the real drug or the sugar pill.
The problem with that study, though, is that it may take months
to not only develop statin-induced muscle pain, but months before it
goes away, so no wonder three-weeks-on, three-weeks-off
may not be long enough for the participants to discern which is which.
But these data are more convincing.
10,000 people were randomized to a statin or sugar pill for a few years.
But they had to stop the study early, because so many more people were dying
in the sugar pill group, and so everyone was then offered the statin.
And what they noted was that there was no excess of reports of
muscle-related adverse effects among patients
assigned to the statin over those assigned to the placebo.
But then, when the placebo phase was over and the people knew
they were on a statin, then they reported more muscle side effects
than those who knew they weren't.
These results illustrate the so-called nocebo effect,
kind of like the opposite of the placebo effect.
Placebo effects are positive consequences falsely attributed to a treatment,
whereas nocebo effects are negative consequences falsely attributed
to a treatment, as was evidently seen here, as there was an excess rate of
muscle-related adverse effects reported only when patients and their doctors
were aware that statin therapy was being used and not when it was being concealed.
They hope these results will help assure both physicians and patients that most
adverse effects associated with statins are not actually caused by the drug
and should help counter exaggerated claims about statin-related side effects.
It's these kinds of results from placebo-controlled randomized trials
that are said to have shown definitively that almost all of the symptomatic
adverse events that are attributed to statin therapy in routine practice
are not actually caused by the drug. Now only a few patients will believe
this, that their statin-associated muscle symptoms
are of psychogenic origin, meaning all just in their head,
but their denial may have deadly consequences.
Discontinuing statin treatment may be a life-threatening mistake.
Here's the mortality of those who stopped their statins after having
a possible adverse reaction compared to those who stuck with them.
This translates into about 1 excess death for every 83 patients
who discontinued treatment within a four-year period. So when there are
media reports about statin side effects and people stop taking them,
this could result in thousands of fatal and disabling heart attacks and strokes
which would otherwise have been avoided.
Seldom in the history of modern therapeutics have the substantial
proven benefits of a treatment been compromised to such an extent
by serious misrepresentations of the evidence for its safety.
But is it a misrepresentation to suggest statin therapy causes
side effects in up to a fifth of patients?
That is actually what you see in clinical practice.
Between 10% to 25% of patients placed on statins complain of muscle problems,
but because we don't see anywhere near those kinds of numbers
in controlled trials, patients are accused of being confused.
Why in clinical trials is the incidence of side effects from statins so low,
but out in the real world appear to be so high?
For example, take this meta- analysis of clinical trials,
finding muscle problems not in 1 in 5, but only 1 in 2,000 patients.
So hey, maybe everyone over a certain age should be on them.
But, of course, every single one of those trials was funded
by the statin manufacturers themselves.
So for example, how could the randomized controlled trials miss detecting
statin-related adverse side effects such as muscle pain? By not asking.
A review of 44 statin trials revealed that only one directly asked
about muscle-related adverse effects.
So are the vast majority of side effects just being missed in all these trials,
or are the vast majority of side effects seen in clinical practice
just some figment of patients' imagination?
The bottom line: we don't know,
but there is certainly an urgent need to figure it out.