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The recently published statin-discontinuation trial 
has been celebrated in the palliative care community.  It’s message is clear – go ahead and stop
statins in patients nearing the end of life.

Or is it?

I’ll offer a contrarian viewpoint: the trial does not reliably
prove that people are helped by stopping statins in the final year or so of
life.

Why this “downer” message?
It’s because the study had insufficient power to assess if there are clinically
meaningful differences between people who were randomized to stop their statin
and those who were randomized to continue.  This is no fault of the investigators; the
study was carefully planned and thoughtfully designed.   However, participants lived three times longer
than expected (an average of 9 months, compared with a projected average of 3
months).  As a result, the original
sample size projections and outcome analysis were jettisoned.  In consultation with the trial’s data safety
and monitoring board, a new outcome of 60-day mortality was substituted.

The results showed that 23.8% of people who stopped statins
died within 60 days, compared with 20.3% who continued statins – a difference
of 3.5%.   In other words, if you took
100 people nearing the end of life and stopped their statin, 3 ½ more of them would
die because you stopped the statin than if you had continued statin therapy.  But, because the sample size of the study was
relatively small (381), there is a lot of uncertainty in that estimate.  The true effect of discontinuing statins
could be anywhere from causing 3 ½ fewer deaths to causing 10 ½ more deaths.   (This is based on the stated 90% confidence
intervals of -3.5% to 10.5%)

What does this mean in plain English?  Stopping statins may cause more people to
die.  It may cause fewer people to
die.  It may make no difference.  We just don’t know.   In contrast, it is incorrect to say that this
trial proves that stopping statins has no effect on mortality.

Fortunately (or not), death is not the only outcome that’s important
to people with advanced terminal disease.
The trial revealed some interesting findings around quality of
life.  People who stopped statins had
better “total” quality of life on a score-based measure.  However, the main factors that contributed to
these better scores were perceptions of having better support and well-being,
whereas physical and other elements of quality of life were no different.  Similarly, physical symptoms and performance
status were similar between people who continued vs. stopped statins.   It’s hard to know what to make of these
results; they are intriguing, but hardly an unequivocal endorsement for
stopping statins.

This is not to say that statins are harmless.  Their side effects are well-documented,
although the frequency of perhaps their most important side effect – a feeling
of muscle aches and malaise – has been very difficult to pin down.  (These symptoms occur reasonably often, but in many if not most cases they are not due to statins).  There has also been concern that statins
might worsen cognitive function by interfering with lipid metabolism in the
brain.  Recent reviews 
on this topic are reassuring, although statins in late life probably do not confer cognitive benefits either.

Does the lack of a clear positive result from the statin
discontinuation trial mean that we should continue statins for all people with
advanced terminal illness?  Of course
not.  This decision should be guided by
the patient’s goals of care, their actual experience with and potential side
effects from statins, and so forth.  Most
studies do not provide an unequivocal answer to clinical questions, and this study
is no different.  Yet, it does provide
useful information that deepens our understanding of the potential benefits and
harms of statins in this setting.  For that
we should thank the investigators and all of the people who participated in the
trial.

by: Mike Steinman

This Post Has 3 Comments

  1. Thank you for expressing my thoughts exactly. Palliative care should be the exact opposite of the "one size fits all mentality." As a geriatrician as well as a palliative medicine practitioner, I'm all for stopping harmful or useless drugs, but these should be thoughtful, individualized decisions.

  2. Excellent review and commentary on this recent interesting article, Mike. Thanks very much. One thing I will add is about the lack of evidence for the benefit of statins in older patients (>75 years), in whom we already base our clinical decisions on our beliefs and patient preferences. For "older patients" with advanced and life-limiting illness, this study may help with bolstering our discussions about discontinuing statins.
    It's interesting that some of our "quality measures" evaluates our care based on statin use and LDL levels in these old-old patients with and without advanced illness.

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