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
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
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
by: Mike Steinman