title: Cholesterol-lowering interventions and stroke: Insights from IMPROVE-IT.
abstract: The relationship of cholesterol with stroke is much less clear than its relationship with myocardial infarction, thus confounding the interpretation of results with cholesterol-lowering trials. Because for long time the only lipid-lowering intervention reducing stroke was statins, it has been actually argued that reduction in stroke found in statin trials is not due to statins' ability to reduce LDL cholesterol, but to other "pleiotropic" effects, unrelated to cholesterol lowering. In re-analyzing the relationship of cholesterol lowering versus changes in the risk of stroke in a meta-regression of all cholesterol-lowering interventions, including also non-statin interventions, we had previously reached the opposite conclusion: that some reduction in stroke has to be expected proportional to cholesterol reduction. We had predicted that a 1% reduction of total cholesterol-no matter by what intervention produced-was associated with a 0.8% relative risk reduction of stroke. Data from the recently published Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) now offer a clear proof of this concept, demonstrating that pure cholesterol lowering, as obtained with ezetimibe, plays an important role in reducing stroke. IMPROVE-IT data, showing a 13.3% reduction in total cholesterol at one year in association with a hazard ratio (HR) of 0.86 for total stroke during the trial, are very closely aligned with the relative risk of 0.90 predicted on the basis of the totality of lipid lowering interventions. These data are important to predict stroke outcomes in currently ongoing trials now testing PCSK9 or cholesterol ester transfer protein inhibitors.
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Tanya
authors.initials: T
authors.lastname: Salvatore
authors.affiliation: Hematology & Oncology, Therapeutic Science & Strategy Unit, Quintiles, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
mesh_terms: D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008078:Cholesterol, LDL / Q000378:metabolism*; D002986:Clinical Trials as Topic; D000069438:Ezetimibe / Q000737:chemistry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000091362:PCSK9 Inhibitors; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D016896:Treatment Outcome; D000071449:Proprotein Convertase 9
chemical_list: D002784:Cholesterol; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Cholesterol; Cholesterol lowering; Epidemiology; Ezetimibe; Risk prediction; Statins; Stroke