THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. WattsStrategies to alter the trajectory of atherosclerotic cardiovascular diseasePackard, Chris J.Author Information Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland Correspondence to Chris J. Packard, Professor, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, Scotland. Tel: +44 141 330 2677; e-mail: [email protected] Current Opinion in Lipidology: December 2019 - Volume 30 - Issue 6 - p 438-445 doi: 10.1097/MOL.0000000000000643 Buy Metrics Abstract Purpose of review Cardiovascular disease prevention trials of lipid lowering with statins have shown unexpected long-term benefits after the formal randomized treatment stopped. This finding needs further exploration because it raises the possibility that the trajectory of the disease can be modified. Recent findings Extended follow up data are now available from further major primary prevention studies and from meta-analyses of the legacy effect of statin trials. New outcome studies have been proposed and launched to test the ability of early intervention to slow or regress atherosclerosis. Summary Legacy effects are apparent in trials of LDL lowering in hypercholesterolemic and hypertensive patient cohorts. Over follow up periods of decades, both cardiovascular mortality and all-cause mortality are reduced in individuals who received 3 to 5 years of statin therapy. The phenomenon is observed also in studies of intensive glycemic control suggesting that it is possible to impact plaque development with long-term beneficial consequences. Novel strategies for primary prevention are being devised that include the early use of both prolonged-moderate and short-term aggressive LDL lowering. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.