10 / 16
EXPERT OPINION
My approach to the patient with
memory loss who needs a statin
By Dr Karol Watson and Dr Tamer Sallam
Statins are among the most powerful cholesterol-lowering medications, and they are also
associated with the greatest cardiovascular risk reduction. For these reasons, the 2013
American College of Cardiology–American Heart Association (ACC–AHA) cholesterol
guidelines recommend statin therapy for patients at elevated cardiovascular risk. When
we encounter such a patient, our approach is to prescribe moderate- or high-intensity statin
therapy by the guidelines. But what if the patient has memory loss?
I
f a patient’s major threat to life
is an atherosclerotic cardiovas-
cular disease (ASCVD), a statin
is still indicated. It may, in fact,
protect the patient from further
cognitive decline due to the vas-
cular protective benefits. Also, it
may protect the patient from stroke
and vascular dementia, the second
most common cause of dementia.
In addition, ASCVD risk reduction
benefits may be seen within the first
2 years of beginning statin therapy.
Therefore, if the patient has a rea-
sonable quality of life and at least a
2-year life expectancy, statin therapy
is appropriate. But what if a patient
develops memory problems while on
statin therapy? Muscular symptoms
are well-known statin side effects,
but recently memory problems have
been attributed to some to statins
(whether correctly or incorrectly).
In 2012, after receiving reports
that some statin users experienced
short-term memory lapses, the US
Dood and Drug Administration
(FDA) released an advisory saying
that it had investigated “... reports of
cognitive impairment from statin use
for several years....” The symptoms,
they said, were nonspecific and de-
scribed as unfocused thinking. The
US FDA concluded that these “...
symptoms were not serious and were
reversible within a few weeks after
the patient stopped using the statin.”
But do statins really cause memory
impairment? Mild memory loss is
commonly seen in clinical practice.
Most cases are due to normal ag-
ing, but progressive and significant
memory loss may signal a more seri-
ous condition such as dementia. The
statin clinical trials have been incon-
sistent about cognition. Statins have
been associated with better cognition
in observational trials, but the only
randomised controlled trial of statin
therapy performed exclusively in old-
er individuals, the PROSPER trial,
conducted neurocognitive testing
and found no differences between
groups (neither harm nor benefit).
More intriguingly, results of a recent
analysis of 482,543 statin users and
26,484 users of other lipid-lowering
agents, showed the same percentage
in each group reporting short-term
memory loss after beginning therapy.
So why might patients who are newly
prescribed statin therapy report more
memory problems? There is a well-
known “detection bias,” whereby
people are more likely to recognise
health problems when they start a
newmedication. Also, memory prob-
lems are common. We often forget
where we put our keys or forget an
acquaintance’s name; however, pa-
tients may be more likely to blame
memory problems on a new drug.
Also, when patients are prescribed
a new medication, they are likely to
see a clinician more often, which can
also add to detection bias.
So, our approach to the patient
with memory problems who need
a statin is this: before prescribing a
statin, and as part of comprehensive
lifestyle assessment, we take a brief
history of muscular symptoms and
memory symptoms. Common ques-
tions we ask are: Do you exercise
regularly? Do you have muscle or
joint pain? How often do you take
any pain relievers for this pain? In
regard to cognition, we ask about
common memory complaints such as
minor forgetfulness or word-finding
difficulties. We may ask: Do you ever
have minor absent-mindedness such
as forgetting where you put your keys
or why you went into a certain room?
Do you ever find a certain word “on
the tip of your tongue” but are unable
to find the word? Do you ever forget
the name of an acquaintance? The
purpose of such questions is to cre-
ate a baseline for comparison should
future symptoms arise. If the patient
does complain of symptoms that he/
she is certain are attributable to the
statin, we hold the statin to see if
there is clear symptom resolution. If
there is, we usually rechallenge the
patient with a different statin, a dif-
ferent dose of the same statin, or a
different dosing schedule. We often
go to the lowest dose of our statin of
choice and give alternate-day dosing.
This is a strategy that has been tested
for statin-intolerant patients using
atorvastatin and rosuvastatin. Once
we find a dose/dosing schedule that
the patient can tolerate, we reinforce
adherence. Formal cognitive testing
is not usually necessary. Ultimately,
whether the patient has cognitive
impairment or not, before initiating
statin therapy we recommend a cli-
nician-patient discussion as outlined
in the 2013 ACC–AHA cholesterol
guidelines to discuss the potential
for ASCVD risk reduction, possible
adverse effects, potential drug–drug
interactions and patient preferences.
Dr Karol Watson is Professor of
Medicine/Cardiology and a board-
certified, full-time cardiologist at
the Geffen School of Medicine
at the University of California,
and Dr Tamer Sallam is Assistant
Professor of Medicine at the David
Geffen School of Medicine at UCLA
and a clinical cardiologist at Ronald
Reagan UCLA Medical Center.
EXPERT COMMENTARY
Penalty of
nonadherence to statin
therapy by women
By Dr Peter Lin
W
e have always known that
many patients are nonad-
herent to therapy. We have
also known that nonadherence leads
to increased risks for our patients. Yet
when we see that patients have not
renewed their medications, we do not
hit the panic button. In a sense, we do
not see nonadherence as an immedi-
ate concern.
This study looked at over 42,000
women taking statin therapy. The
researchers divided them into two
groups based on their adherence rates.
Good adherence was defined as tak-
ing prescribed medications more than
80% of the time; poor adherence was
defined as less than 80%.
The adherent patients had a hazard
ratio of 0.78 (95% CI, 0.65–0.94) for
acute cardiovascular events. This 12%
reduction is a significant amount and
the only thing that the patients had
to do was to take their pill every day.
Perhaps instead of saying that
the adherent patients had a benefit,
maybe we should start saying that the
nonadherent patients will have to pay
a penalty by having an acute event.
That concept of penalty might wake us
all up and force all of us to pay more
attention to this issue of adherence.
Dr Peter Lin is
Director of Primary
Care Initiatives
at the Canadian
Heart Research
Centre, Canada.
Statin adherence reduces the risk of acute cardiovascular events
among women
BMJ Open
Take-home message
•
In this retrospective analysis, the authors evaluated the effect of statins
used for primary prevention in 42,807 women aged 45 to 64 years over
a 3-year follow-up period while taking account of time dependence of
adherence and confounders. The hazard ratio for acute cardiovascular
events was 0.78 for women who remained adherent to statin therapy
compared with those who were non-adherent. The women who were
adherent to treatment had a lower risk of low-energy fractures compared
with those not adhering to therapy, suggesting a possible healthy-
adherer effect.
•
Adherence to statins for primary prevention in women reduces the risk
of a subsequent cardiovascular event by one-fifth, but this may be due
in part to the healthy-adherer effect.
Abstract
OBJECTIVES
Previous studies on the
effect of statin adherence on cardio-
vascular events in the primary preven-
tion of cardiovascular disease have
adjusted for time-dependent con-
founding, but potentially introduced
bias into their estimates as adherence
and confounders were measured si-
multaneously. We aimed to evaluate
the effect when accounting for time-
dependent confounding affected by
previous adherence as well as time
sequence between factors.
DESIGN
Retrospective cohort study.
SETTING
Finnish healthcare registers.
PARTICIPANTS
Women aged 45–64
years initiating statin use for primary
prevention of cardiovascular disease
in 2001–2004 (n = 42807).
OUTCOMES
Acute cardiovascular event
defined as a composite of acute coro-
nary syndrome and acute ischaemic
stroke was our primary outcome.
Low-energy fractures were used as a
negative control outcome to evaluate
the healthy-adherer effect.
RESULTS
During the 3-year follow-up,
474 women experienced the primary
outcome event and 557 suffered a
low-energy fracture. The causal HR
estimated with marginal structural
model for acute cardiovascular events
for all the women who remained
adherent (proportion of days cov-
ered ≥80%) to statin therapy during
the previous adherence assessment
year was 0.78 (95% CI 0.65–0.94)
when compared with everybody
remaining non-adherent (proportion
of days covered <80%). The result
was robust against alternative model
specifications. Statin adherers had a
potentially reduced risk of experienc-
ing low-energy fractures compared
with non-adherers (HR 0.90, 95% CI
0.76–1.07).
CONCLUSIONS
Our study, which took
into account the time dependence of
adherence and confounders, as well
as temporal order between these
factors, is support for the concept
that adherence to statins in women
in primary prevention decreases the
risk of acute cardiovascular events
by about one-fifth in comparison to
non-adherence. However, part of the
observed effect of statin adherence
on acute cardiovascular events may
be due to the healthy-adherer effect.
Statin adherence and risk of acute
cardiovascular events among
women: A cohort study accounting
for time-dependent confounding
affected by previous adherence
.
BMJ Open
2016;6(6)e011306,
Lavikainen P, Helin-Salmivaara A,
Eerola M, et al.
METABOLIC & ENDOCRINE DISORDERS
PRACTICEUPDATE ENDOCRINOLOGY
10