More on statins: your baseline LDL cholesterol does matter dramatically

https://jamanetwork.com/journals/jama/article-abstract/2678614?redirect=true

Surprisingly no advantage for Stroke

This very interesting meta-analysis should engage researchers to reconsider the design of future trials with lipid-lowering drugs including PCSK9 i.
Patients with low LDL cholesterol at baseline don't benefit from statins. This si not completely new but this is nicely showed by this work.
The lack of efficacy of statins for stroke is more disturbing. It means that we need the raw data of SPARCL to verify this trial.
1/ Should we reconsider prescriptions of statins according to the baseline level of LDL cholesterol?
Lin disaggrees
https://www.practiceupdate.com/c/66963/67/17/?elsca1=emc_enews_weekinreview&elsca2=email&elsca3=practiceupdate_cdd&elsca4=cdd&elsca5=newsletter&rid=MzMwNjc5MDUwNzk4S0&lid=10332481
2/ This meta-analysis of 34 trials was conducted to evaluate the effect of baseline LDL-C levels on mortality following the use of LDL-C–lowering drugs. All-cause mortality was 7.08% in those treated with more intensive therapy vs 7.70% in those who received less intensive therapy, but this varied according to baseline LDL-C levels. It is a true dilemma.
3/ The reduction in all-cause mortality was greater with a higher baseline LDL-C level but only with a baseline LDL-C ≥100 mg/dL. Similarly, cardiovascular mortality was lower in those receiving intensive therapy than those treated with less intensive therapy, and, again, the greater benefit obtained at higher baseline LDL-C levels was only seen for patients with a baseline LDL-C ≥100 mg/dL. The greatest mortality reductions were seen among people with a baseline LDL-C level ≥160 mg/dL.

4/ As LDL cholesterol is calculated and doesn't figure the reality of LDL particles one can take some distance with the statin dogma. 

However there as some biases:

1/ "Interestingly, the older studies, such as 4S, enrolled patients with very high LDL-C because none of the participants was on any treatment. These were also the statin vs true placebo trials. So, maybe the benefit that we are seeing in patients with a high baseline LDL-C is based on this phenomenon. However, over time, we treated to lower and lower levels of LDL-C, and hence the newer trials enrolled patients with lower baseline LDL-C because those with higher LDL-C levels needed to be treated already, and therefore had lower LDL-C at baseline. Also, as statins became standard of care, the newer trials had to test statins against statins as opposed to a true placebo. Therefore, these newer studies would have a harder time showing benefits relative to death, in contrast to the older trials, which studied statins against placebo." Good point.
2/ "The final concern with this article is that the primary and secondary prevention studies were mixed together. The two groups would have very different death rates, and hence some effort should have been made to separate them."

https://www.practiceupdate.com/c/66963/67/17/?elsca1=emc_enews_weekinreview&elsca2=email&elsca3=practiceupdate_cdd&elsca4=cdd&elsca5=newsletter&rid=MzMwNjc5MDUwNzk4S0&lid=10332481

So keeping in mind that the higher the LDL at baseline the more benefit the patient will obtain with statins is fair.
Treating patients without symptoms and moderate elevation of LDL cholesterol is not evidence-based.

References

1/ Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383-1389. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)90566-5/abstract
2/ LaRosa JC1, Grundy SM, Waters DD, et al; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. http://www.nejm.org/doi/10.1056/NEJMoa050461
3/ SPARCL https://www.nejm.org/doi/full/10.1056/NEJMoa061894