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

Background: In the Systolic Hypertension in Europe trial (NCT02088450), we investigated whether systolic blood pressure variability determines prognosis over and beyond level. Methods: Using a computerised random function and a double-blind design, we randomly allocated 4695 patients (>= 60 years) with isolated systolic hypertension (160-219/= 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 = 0.058). 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. Conclusions: The 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.