title: More Versus Less Intensive Blood Pressure-Lowering Strategy: Cumulative Evidence and Trial Sequential Analysis.
abstract: Several randomized trials compared a more versus less intensive blood pressure-lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure-lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure-lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervention Trial) study, thereby providing firm evidence of superiority of a more intensive over a less intensive blood pressure-lowering strategy. For cardiovascular death and heart failure, the cumulative Z curve crossed the conventional significance boundary, but not the sequential monitoring boundary, after SPRINT. For all-cause death, the SPRINT trial pushed the cumulative Z curve away from the futility area, without reaching the conventional significance boundary. We conclude that evidence accrued to date strongly supports the superiority of a more intensive versus a less intensive blood pressure-lowering strategy for prevention of stroke and myocardial infarction. Cardiovascular death and heart failure are likely to be reduced by a more intensive blood pressure-lowering strategy, but evidence is not yet conclusive.
authors.affiliation: From the Department of Medicine, Hospital of Assisi, Italy (P.V.); Cardiology and Cardiovascular Pathophysiology, Hospital S.M. della Misericordia, Perugia, Italy (F.A.); Royal Cornwall Hospitals, NHS Trust, Truro, Cornwall, UnitedKingdom (G.G.); and Department of Medicine, University of Perugia, Italy (G.R.). verdec@tin.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Verdecchia
authors.affiliation: From the Department of Medicine, Hospital of Assisi, Italy (P.V.); Cardiology and Cardiovascular Pathophysiology, Hospital S.M. della Misericordia, Perugia, Italy (F.A.); Royal Cornwall Hospitals, NHS Trust, Truro, Cornwall, UnitedKingdom (G.G.); and Department of Medicine, University of Perugia, Italy (G.R.).
authors.forename: Fabio
authors.initials: F
authors.lastname: Angeli
authors.affiliation: From the Department of Medicine, Hospital of Assisi, Italy (P.V.); Cardiology and Cardiovascular Pathophysiology, Hospital S.M. della Misericordia, Perugia, Italy (F.A.); Royal Cornwall Hospitals, NHS Trust, Truro, Cornwall, UnitedKingdom (G.G.); and Department of Medicine, University of Perugia, Italy (G.R.).
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gentile
authors.affiliation: From the Department of Medicine, Hospital of Assisi, Italy (P.V.); Cardiology and Cardiovascular Pathophysiology, Hospital S.M. della Misericordia, Perugia, Italy (F.A.); Royal Cornwall Hospitals, NHS Trust, Truro, Cornwall, UnitedKingdom (G.G.); and Department of Medicine, University of Perugia, Italy (G.R.).
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Reboldi
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: D000959:Antihypertensive Agents
keywords: blood pressure; heart failure; hypertension; myocardial infarction; stroke