There are several topics that my elderly patients discuss at every appointment, interaction, or social event.
- The traffic on Eagle Road (the busiest thoroughfare in Idaho) and how “these darn Californians keep ruining our state.”
- How “we really need rain” since last year’s fire season “was brutal.”
- COVID
But on a broader scale, the topic of Cholesterol Medications in this population continues to be a somewhat more pressing issue in clinical circles than even the most viscous of traffic jams on Eagle Road, and the STAREE trial (Statin Therapy for Reducing Events in the Elderly) sought to give us a better understanding of this topic, which I first discussed in THIS ARTICLE.
The STAREE trial enrolled 9971 patients aged 70 and up WITHOUT a history of cardiovascular disease.
-This means they hadn’t had a cardiovascular event, like a heart attack or stroke. It does NOT mean that they didn’t have a positive CAC score or “subclinical atherosclerosis.”
Over half of those enrolled were women! This is great!
-On a side note, after I perused the “Methods” section of the paper, it didn’t appear that the researchers had any difficulty identifying who was a “man” and who was a “woman” in this trial. Smart investigators! Maybe they can help out the WNBA as their next project.
Anyway, the folks in this study were randomized into a group receiving Atorvastatin 40 mg (this is a “high-intensity” statin) or placebo and were followed for 5.9 years to see if major adverse cardiovascular events (MACE) were reduced. Additional outcomes of interest were all-cause mortality, dementia, and disability-free survival.
And the results were quite impressive for reduction in cardiovascular events, with a relative risk reduction of 30% in those receiving the statin (4.6% absolute risk reduction). This translates into an NNT (Number Needed to Treat) of 37, which seems pretty good. ATORVA will make you IMMORTA! (That was a stretch).
But it’s also a stretch to think that a statin is going to reduce your risk of dying from other causes beyond cardiovascular disease.
Indeed, all-cause mortality was neutral, disability-free survival was neutral, and dementia was neutral. Not surprisingly, there were more muscle-related side effects in the statin-treated folks as well as more diabetes-related events, including “medically important” muscle and blood sugar events (whatever that means). I always think it’s important when muscles are hurting and when people are having blood sugar dysregulation, but we can set that aside for now.
Of note, while most of these groups were “trending in the right direction” in regards to MACE reduction, there were several subgroups who had an overall neutral result on subanalysis:
- Those with BMI <25
- Those with eGFR (measure of kidney function) <60
- Those with the lowest systolic blood pressure
- Women
- Those in the two highest tertiles of HDL-C levels
So let the speculations begin! But here are a few thoughts:
- I’d love to see this trial repeated with a lower dose of statin in combination with other therapies, particularly when there is strong data in the elderly for agents such as ezetimibe (see EWTOPIA-75) and PCSK9 inhibitor monoclonal antibodies (see FOURIER and FOURIER-OLE subanalysis of the elderly).
- Perhaps combination therapy could mitigate musculoskeletal side effects and prevent glycemic excursions, which could perhaps translate into more disability-free years…or not.
- Perhaps when folks are living longer due to NOT having cardiovascular events, they may end up at higher risk of having other health conditions due to survival bias…everyone dies of something.
- This reinforces the safety, but neutrality, of statins for dementia at the population level. Hopefully with further research we can have a more individualized approach for preventing neurodegeneration. However, high-intensity statin therapy, outside of acute coronary syndromes, is a pretty lazy approach to lipid-lowering therapy in this era of precision medicine. And although what’s good for the heart is generally good for the brain, there are real nuances with cholesterol homeostasis in the CNS as I discuss HERE.
It seems that statins can still have a STAR-ring role when it comes to reducing risk of cardiovascular events in the geriatric population. However, whether you’re on a statin or not, you will have to STARE death in the face at some point. But hopefully you’re disability and dementia-free whenever your time comes😊
