Randomised Double-Blind Comparison of Placebo and Active Drugs for Effects on Risks Associated with Blood Pressure Variability in the Systolic Hypertension in Europe Trial

BackgroundIn the Systolic Hypertension in Europe trial (NCT02088450), we investigated whether systolic blood pressure variability determines prognosis over and beyond level.MethodsUsing a computerised random function and a double-blind design, we randomly allocated 4695 patients (≥60 years) with isolated systolic hypertension (160–219/n = 286) or cardiovascular (n = 150) mortality or cardiovascular (n = 347), cerebrovascular (n = 133) or cardiac (n = 217) endpoints.FindingsAt 2 years, mean between-group differences were 10.5 mm Hg (pvs. high VIM had similar event rates (p≥0.14). Low vs. high WVV was not associated with event rates (p≥0.095), except for total and cardiovascular mortality on active treatment, which were higher with low WVV (p≤0.0003). In multivariable-adjusted Cox models, SBP predicted all endpoints (p≤0.0043), whereas VIM did not predict any (p≥0.058). Except for an inverse association with total mortality (p = 0.042), WVV was not predictive (p≥0.15). Sensitivity analyses, from which we excluded blood pressure readings within 6 months after randomisation, 6 months prior to an event or both were confirmatory.ConclusionsThe double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP. Higher blood pressure level, but not higher variability, predicted risk.Trial RegistrationClinicalTrials.gov NCT02088450