A Tale of Two Trials: Reconciling Differences in Results by Exploring Heterogeneous Treatment Effects

Editorials7 March 2017A Tale of Two Trials: Reconciling Differences in Results by Exploring Heterogeneous Treatment EffectsSanjay Kaul, MDSanjay Kaul, MDFrom Cedars-Sinai Medical Center, Los Angeles, California.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2818 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the past several years, 3 large, well-designed, rigorously conducted treat-to-target randomized clinical trials (ACCORD [Action to Control Cardiovascular Risk in Diabetes], SPS3 [Secondary Prevention of Small Subcortical Strokes Trial], and SPRINT [Systolic Blood Pressure Intervention Trial], which together enrolled 17 114 participants) have been done. These trials have explored whether blood pressure (BP) goals that are lower than those usually recommended for treatment of hypertension would have greater benefit for prevention of cardiovascular disease (CVD) and stroke (1–3). They have yielded divergent results about the primary outcome: inconclusive in ACCORD and SPS3 but robustly favorable in SPRINT. Several arguments have ...References1. Cushman WC, Evans GW, Byington RP, Goff DC, Grimm RH, Cutler JA, et al; ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-85. [PMID: 20228401] doi:10.1056/NEJMoa1001286 CrossrefMedlineGoogle Scholar2. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-16. [PMID: 26551272] doi:10.1056/NEJMoa1511939 CrossrefMedlineGoogle Scholar3. Benavente OR, Coffey CS, Conwit R, Hart RG, McClure LA, Pearce LA, et al; SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382:507-15. [PMID: 23726159] doi:10.1016/S0140-6736(13)60852-1 CrossrefMedlineGoogle Scholar4. Oparil S, Lewis CE. Should patients with cardiovascular risk factors receive intensive treatment of hypertension to <120/80 mm Hg target? A protagonist view from the SPRINT trial (Systolic Blood Pressure Intervention Trial). Circulation. 2016;134:1308-1310. [PMID: 27619922] CrossrefMedlineGoogle Scholar5. Lonn EM, Yusuf S. Should patients with cardiovascular risk factors receive intensive treatment of hypertension to <120/80 mm Hg target? An antagonist view from the HOPE-3 trial (Heart Outcomes Evaluation-3). Circulation. 2016;134:1311-1313. [PMID: 27619924] CrossrefMedlineGoogle Scholar6. Kent DM, Nelson J, Dahabreh IJ, Rothwell PM, Altman DG, Hayward RA. Risk and treatment effect heterogeneity: re-analysis of individual participant data from 32 large clinical trials. Int J Epidemiol. 2016. [PMID: 27375287] CrossrefMedlineGoogle Scholar7. Kent DM, Rothwell PM, Ioannidis JP, Altman DG, Hayward RA. Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials. 2010;11:85. [PMID: 20704705] doi:10.1186/1745-6215-11-85 CrossrefMedlineGoogle Scholar8. Basu S, Sussman JB, Hayward RA. Detecting heterogeneous treatment effects to guide personalized blood pressure treatment. A modeling study of randomized clinical trials. Ann Intern Med. 2017;166:354-60. doi:10.7326/M16-1756 LinkGoogle Scholar9. Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-82. [PMID: 27195814] doi:10.1001/jama.2016.7050 CrossrefMedlineGoogle Scholar10. Odden MC, McClure LA, Sawaya BP, White CL, Peralta CA, Field TS, et al. Achieved blood pressure and outcomes in the Secondary Prevention of Small Subcortical Strokes Trial. Hypertension. 2016;67:63-9. [PMID: 26553236] doi:10.1161/HYPERTENSIONAHA.115.06480 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Cedars-Sinai Medical Center, Los Angeles, California.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2818.Corresponding Author: Sanjay Kaul, MD, Division of Cardiology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 790W, Los Angeles, CA 90049; e-mail, [email protected]org.This article was published at Annals.org on 3 January 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDetecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment Sanjay Basu , Jeremy B. Sussman , and Rod A. Hayward Metrics Cited byHeterogenous treatment effects: secrets for a reliable treat-to-target trial?EBM vs. EBM 7 March 2017Volume 166, Issue 5Page: 370-372KeywordsBlood pressureCardiovascular diseasesClinical trialsHazard ratioHypertensionMyocardial infarctionStatistical dataStrokeType 2 diabetes ePublished: 3 January 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...