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.