P5729Restricted mean survival time analysis to assess efficacy and safety of intensive vs standard blood pressure treatment goals as a function of age: insights from the SPRINT trial

Abstract

Abstract Background Blood pressure (BP) treatment targets in older adults (≥75 years) remain controversial. Restricted mean survival time (RMST) analysis is an alternative to hazard ratios (decreased reliance on proportional hazards assumption) with an intuitive interpretation of a gain or loss in event-free days. This may be valuable when assessing effectiveness and safety of BP treatment as a function of age. Purpose Determine differences in event-free time (days) between intensive (≤120 mm Hg) and conservative (≤140 mm Hg) BP treatment stratified by age categories. Methods Post hoc analysis to estimate RMST using publicly available SPRINT trial dataset for the primary SPRINT composite cardiovascular outcome and a 6-point secondary safety outcome (hypotension, syncope, bradycardia, electrolyte abnormality, injurious falls, or acute kidney injury) that resulted in emergency department visits or serious adverse events. Results In 9,361 participants the average age was 67.9±9.4 years (≤64 years: n=4,216; 65–74 years: n=2794, ≥75 years: n=2351). Over 5 years, participants in the intensive arm had an extra 13.8 cardiovascular event-free days [(3.9 to 23.6), p=0.006]; this increased to 28.6 days [(3.6 to 53.7), p=0.025] in those ≥75 years. For the 6-point composite safety outcome, participants in the intensive arm had on average significantly fewer safety event-free days compared to the control arm [−37.6 days (−54.2 to −21.1)], p<0.0001; this decreased to −8.6 days [(−43.2 to 26.1), p=0.63] in those ≥75 years. Restricted Mean Survival Time Age Category RMST (Intensive) RMST (Control) RMST (Intensive-Control Difference) P-value (Days, 95% CI) (Days, 95% CI) (Days, 95% CI) Primary SPRINT MACE Outcome All Ages 1441.9 (1435.3 to 1448.5) 1428.1 (1420.9 to 1435.3) 13.8 (3.9 to 23.6) 0.006 <65 years 1411.9 (1404.9 to 1419.0) 1401.8 (1393.4 to 1410.1) 10.2 (−0.7 to 21.1) 0.07 65–74 years 1375.2 (1363.9 to 1386.5) 1369.5 (1358.1 to 1380.9) 5.7 (−10.4 to 21.8) 0.49 ≥75 years 1393.7 (1376.9 to 1410.5) 1365.1 (1346.5 to 1383.7) 28.6 (3.6 to 53.7) 0.025 Primary Composite Safety Outcome All Ages 1370.9 (1358.7 to 1383.3) 1408.6 (1397.5 to 1419.7) −37.6 (−54.2 to−21.1) <0.0001 <65 years 1396.9 (1380.7 to 1413.1) 1439.2 (1425.6 to 1452.8) −42.2 (−63.4 to −21.1) <0.0001 65–74 years 1299.7 (1279.7 to 1319.7) 1347.5 (1330.5 to 1364.5) −47.8 (−74.0 to −21.5) <0.0001 ≥75 years 1187.6 (1162.8 to 1212.4) 1196.2 (1171.9 to 1220.4) −8.6 (−43.2 to 26.1) 0.63 RMST = restricted mean survival time; MAC = major adverse cardiovascular events. Conclusions Compared to controls, intensively treated older adults ≥75 years had larger gains in the primary cardiovascular outcome with similar losses in the composite safety outcome. Acknowledgement/Funding None