The signal in the JUPITER trial may have been due to some subject selection bias. The massively high death rate for all subjects has never really be explained.
So atorvastatin 10 mg reduced ACM by 15% in hypertensive people who didn’t even have dyslipidemia (“total cholesterol concentrations at baseline of ≤6.5 mmol/L”) after 5y?
For JUPITER participants were “apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher”
So both trials are relevant to people here without dyslipidemia who want to act preemptively.
JUPITER used rosuvastatin 20 mg while the other used atorvastatin 10 mg, equivalent to rosuvastatin 5 mg. So it’s not an apple to apple comparison.
For those with diabetes or cataract (or at high risk of these conditions) then atorvastatin seems the best option.
JUPITER is a questionable trial. It was prematurely halted and failed to demonstrate a statistically significant difference in ASCVD mortality. Although it initially indicated a reasonable reduction in all-cause mortality, the difference appeared to diminish over time. Moreover, the authors excluded data from the final months and adjusted the all-cause mortality graph, raising doubts about the trial’s reliability. Overall, it’s challenging to draw meaningful conclusions from this trial, which seems to be more about statistical manipulation than substantial evidence.
In the UK NICE chose atorvastatin as first line because the benefit / side effect profile was seen as the best. The ASCOT trial was a big part of the evidence supporting that.
It’s worth reading the NICE protocol because it specifies when each statin is preferable for a specific individual. CKS is only available in the UK | NICE
There’s also a good nhs england pdf looking at intolerance to statins, what to test for, and what to switch to. statin-intolerance-pathway-v2.pdf (236.0 KB)
This study halted prematurely as well, the end is a follow up, and led to the statistical significant effect, so it is a limitation (see end of LLA in the graph, which also “converged” a bit).
When comparing statins with more or less the same lipid-lowering properties there are still some differences in outcomes.
So, are there some beneficial effects from statins that are not related to their lipid-lowering properties? If so, what are the beneficial side effects of the different statins?
The antiinflammatory affects are probably very important too. The strong short term benefit post a cvd event is probably due to those. But you make a good point, i should have emphasized that NICE regarded the evidence for atorvastatin benefit as strongest.
Each of the statins interact with different liver enzymes which may partially account for different side effects.
P=0.059 so technically not statistically significant, but I am pretty much convinced that atorvastatin reduce all-cause mortality in primary prevention for heart disease.
I did try 20 mg atorvastatin for a few days but I switched back to rosuvastatin. I will try again since the drug pretty much reduces all-cause mortality, all statins cross the BBB, and more importantly it has a lower causal risk of diabetes compared with rosuvastatin. If it wasn’t for the latter I wouldn’t try and switch.
The STAREE trial and STAREE-MIND trial chose 40 mg atorvastatin as well for its research, reading a bit in the supplementary information, they cite research which suggest lipophilic (meaning drugs that can pass the BBB), might be superior for dementia and as many of us know APOB causes Alzheimer’s according to MR studies.
Meanwhile, until we know more about Lipitor vs. Crestor for dementia and Alzheimer’s, for example in E4 carriers of APOE, I think Lipitor is probably better based on current information. The STAREE trial should tell us more? (vs. bempedoic acid, PCSK9i and ezetimibe, I still think statins have more data like for mortality and net benefit, thus they are right now superior?).
Alongside a very likely decrease in all cause mortality, statins like atorvastatin seem good in reducing stroke, that does often reduce healthspan significantly I think, even if they are non-fatal.
Regarding AD, this trial found no cognitive improvement after 24 months of aerobic training + atorvastatin 80 mg + losartan + amlodipine in people at high risk of AD: ClinicalTrials.gov
Assumptions:
The trial was too small?
The effects can only be seen after a longer period of time?
High dose statin is detrimental? (cf. UK Biobank study)
By the way, if I’m correct, with the exception of the French statin cessation study, we won’t get new RCT results regarding statins and cognition until 2025/2026 (see: Rapamycin and risk of cardiovascular disease - #3064 by adssx ). So only retrospective, MR, or animal studies could bring new insights in the meantime. Or an RCT of another lipid-lowering drug (obicetrapib ).
The study doesn’t mask the cessation of the statin with a placebo pill, and the primary outcome is a subjective measurement using EQ-5D scale. The second primary endpoint is total mortality which is hard to detect in 36 months? That doesn’t sound so useful to me. But it has some other secondary outcomes.
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