Cholesterol Lowering and Stroke: No Longer Room for Pleiotropic Effects of Statins - Confirmation from PCSK9 Inhibitor Studies.
Atherosclerosis
Cholesterol
Ezetimibe
Lipid-lowering
PCSK9 inhibitors
Statins
Stroke
Journal
The American journal of medicine
ISSN: 1555-7162
Titre abrégé: Am J Med
Pays: United States
ID NLM: 0267200
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
08
06
2019
revised:
13
06
2019
accepted:
14
06
2019
pubmed:
14
7
2019
medline:
18
4
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
The relationship between cholesterol levels and stroke has been much less clear than the relationship between cholesterol levels and coronary heart disease. This is likely mostly due to the inadequate power of older studies and the low intensity of cholesterol-lowering interventions available at the time. Because a reduction in stroke has been, conversely, clearly observed in trials with statins, for long "pleiotropic" effects of such drugs, unrelated to cholesterol lowering, have been invoked. In a previous analysis of all randomized trials of cholesterol-lowering treatments reporting on stroke we had, however, reached the conclusion that any cholesterol lowering is related to a significant reduction of stroke, in a relationship that appeared to exist for both statin and nonstatin cholesterol-lowering interventions. Outcome results of the FOURIER trial with evolocumab, SPIRE-1 and -2 with bococizumab, and ODYSSEY OUTCOMES trial with alirocumab now offer the opportunity of clearly confirming or confuting this concept. We here report on an updated meta-regression of the relationship of total cholesterol changes that occur with various drugs or treatments and changes in the risk of stroke compared with control. Relative risk (RR) figure found in FOURIER, SPIRE-1/2, and ODYSSEY OUTCOMES (0.79, 0.60, and 0.79) are extremely close to the RRs of 0.79, 0.79, and 0.84, respectively, predicted by our new meta-regression. These findings offer definitive proof that the pure total (and low-density lipoprotein) cholesterol lowering, with any available lipid-lowering intervention, reduces stroke risk proportional to the extent of cholesterol reduction, without the need of invoking "pleiotropic" effects of any such treatment.
Sections du résumé
BACKGROUND
The relationship between cholesterol levels and stroke has been much less clear than the relationship between cholesterol levels and coronary heart disease. This is likely mostly due to the inadequate power of older studies and the low intensity of cholesterol-lowering interventions available at the time. Because a reduction in stroke has been, conversely, clearly observed in trials with statins, for long "pleiotropic" effects of such drugs, unrelated to cholesterol lowering, have been invoked. In a previous analysis of all randomized trials of cholesterol-lowering treatments reporting on stroke we had, however, reached the conclusion that any cholesterol lowering is related to a significant reduction of stroke, in a relationship that appeared to exist for both statin and nonstatin cholesterol-lowering interventions. Outcome results of the FOURIER trial with evolocumab, SPIRE-1 and -2 with bococizumab, and ODYSSEY OUTCOMES trial with alirocumab now offer the opportunity of clearly confirming or confuting this concept.
METHODS
We here report on an updated meta-regression of the relationship of total cholesterol changes that occur with various drugs or treatments and changes in the risk of stroke compared with control.
RESULTS
Relative risk (RR) figure found in FOURIER, SPIRE-1/2, and ODYSSEY OUTCOMES (0.79, 0.60, and 0.79) are extremely close to the RRs of 0.79, 0.79, and 0.84, respectively, predicted by our new meta-regression.
CONCLUSIONS
These findings offer definitive proof that the pure total (and low-density lipoprotein) cholesterol lowering, with any available lipid-lowering intervention, reduces stroke risk proportional to the extent of cholesterol reduction, without the need of invoking "pleiotropic" effects of any such treatment.
Identifiants
pubmed: 31301293
pii: S0002-9343(19)30564-9
doi: 10.1016/j.amjmed.2019.06.029
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Anticholesteremic Agents
0
Cholesterol, LDL
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
PCSK9 Inhibitors
0
bococizumab
45M75JVK38
Cholesterol
97C5T2UQ7J
evolocumab
LKC0U3A8NJ
alirocumab
PP0SHH6V16
Types de publication
Journal Article
Meta-Analysis
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-99.e6Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.