Individual and Joint Effects of Pulse Pressure and Blood Pressure Treatment Intensity on Serious Adverse Events in the SPRINT Trial

Purpose: The objective of this study was to determine individual and joint effects of pulse pressure and blood pressure treatment intensity on serious adverse events in the Systolic Blood Pressure Intervention Trial. Methods: Pulse pressure was calculated by subtracting diastolic blood pressure from systolic blood pressure. Blood pressure treatment intensity goal was ≤140 mm Hg in the control arm and ≤120 mm Hg in the intensive arm. The primary outcome was a 5-point composite of hypotension, syncope, electrolyte abnormalities, acute renal insufficiency, or injurious falls. Results: In 9361 trial participants, the incident rate for the primary outcome per 1000 person-years increased with higher pulse pressure category: ≤49 mmHg: 20.4 (17.2-24.1), 50-59 mmHg: 24.5 (21.3-28.2), 60-69 mmHg: 31.7 (27.7-36.2), ≥70 mmHg: 44.6 (39.8-49.9; P_trend <.0001; hazard ratio [HR] of pulse pressure [every 10 mm Hg] 1.23; 95% confidence interval [CI], 1.18-1.28). The intensive treatment arm had a higher incidence rate of serious adverse events than the control arm (34.2, 95% CI, 31.2-37.3, vs 26.0, 95% CI, 23.4-28.8, P =.0001; HR 1.32; 95% CI, 1.15-1.51). The combined effect was not significant in the relative risk scale (HR 0.97, P_interaction =.48) but was significant in the risk difference scale (P =.027), contributing 2.5 additional serious adverse events per 1000 person-years for every 10 mm Hg increase in pulse pressure in excess of the individual effects of pulse pressure and treatment intensity. Conclusions: Wider pulse pressure and intensive blood pressure treatment were individually associated with the composite adverse event outcome. A modest effect modification of pulse pressure and treatment intensity led to additional adverse events when both were present. Clinicians should use caution when treating older patients with elevated pulse pressure to an intensive blood pressure treatment target.