HomeStrokeVol. 53, No. 11Is It About the Destination or About the Journey? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBIs It About the Destination or About the Journey? Dylan Blacquiere, Holly Sim and Dar Dowlatshahi Dylan BlacquiereDylan Blacquiere https://orcid.org/0000-0002-8421-2646 Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Canada (D.B., D.D.). Search for more papers by this author , Holly SimHolly Sim https://orcid.org/0000-0002-7721-0191 Department of Medicine, University of Ottawa, Canada (H.S.). Search for more papers by this author and Dar DowlatshahiDar Dowlatshahi Correspondence to: Dar Dowlatshahi, MD, PhD, The Ottawa Hospital Civic Campus, Division of Neurology, 1053 Carling Ave, Room C2182b, Ottawa ON, K1Y 4E9, Canada. Email E-mail Address: [email protected] https://orcid.org/0000-0003-1379-3612 Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Canada (D.B., D.D.). Search for more papers by this author Originally published26 Sep 2022https://doi.org/10.1161/STROKEAHA.122.040567Stroke. 2022;53:3268–3269This article is a commentary on the followingYield of Dual Therapy With Statin and Ezetimibe in the Treat Stroke to Target Trialis related toNovember 2022 Stroke HighlightsOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 26, 2022: Ahead of Print See related article, p 3260In a post hoc analysis of the TST trial (Treat Stroke to Target),1 Amarenco et al2 provide data showing patients treated with ezetimibe in addition to statin therapy with a target LDL (low-density lipoprotein) of <70 mg/dL had a reduction in major vascular events as compared with patients with a target of LDL<100 mg/dL; this effect was not seen with statin monotherapy, despite reaching comparable LDL targets. This finding likely reflects a higher baseline LDL in those patients prescribed dual therapy, which resulted in a higher magnitude of LDL reduction.The role of cholesterol reduction in the prevention of vascular disease has long been established. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol) in 2006 was pivotal in showing that that atorvastatin therapy was associated with reduced stroke risk.3 Thereafter, recurrent stroke risk reduction was thought to be related to a statin-specific mechanism of action; patients were prescribed statins irrespective of lipid profile. Subsequent trials showed that the more aggressive the target, the better.1,4 The TST trial, in particular, demonstrated that therapy toward a lower LDL target of 70 mg/dL was associated with reduced risk of stroke when compared with a more lenient 100 mg/dL. Clinical practice guidelines were adapted to reflect this more aggressive target,5 but the choice of agents for LDL reduction was left to the discretion of treating clinicians. In the cardiology literature, studies such as the IMPROVE-IT trial (Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes) have shown that nonstatin agents may offer additional benefit when added to statins, both in achieving more aggressive LDL targets, and in reducing recurrent coronary syndromes.6 In contrast, stroke clinicians have generally continued to use statins as the mainstay of therapy, with agents like ezetimibe as adjuncts where targets are not achieved.Despite the usual caveats associated with post hoc analyses, including the limited ability to assess for subgroup effects (sex, age), this study by Amarenco and colleagues makes intuitive sense and supports a personalized approach to secondary prevention. Moreover, the results are generalizable as the patients are relatively representative of those seen in stroke prevention clinics across many jurisdictions, with a high proportion of statin-naive patients. Finally, the study supports the notion that the magnitude of LDL reduction may be equally, if not more, important than the LDL target itself. It may not just be the LDL target that provides the benefit, but rather how we reach that target, and the place where we started from.Article InformationDisclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.This manuscript was sent to Hanne Christensen, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition.For Disclosures, see page 3268.Correspondence to: Dar Dowlatshahi, MD, PhD, The Ottawa Hospital Civic Campus, Division of Neurology, 1053 Carling Ave, Room C2182b, Ottawa ON, K1Y 4E9, Canada. Email [email protected]ca