Adam P Bress1, Tom Greene2, Catherine G Derington2, Jincheng Shen2, Yizhe Xu2, Yiyi Zhang3, Jian Ying4, Brandon K Bellows3, William C Cushman5, Paul K Whelton6, Nicholas M Pajewski7, David Reboussin7, Srinivasan Beddu8, Rachel Hess2, Jennifer S Herrick2, Zugui Zhang9, Paul Kolm10, Robert W Yeh11, Sanjay Basu12, William S Weintraub13, Andrew E Moran3. 1. Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA. Electronic address: adam.bress@hsc.utah.edu. 2. Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, USA. 3. Division of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA. 4. Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. 5. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA; Medical Service, Memphis VA Medical Center, Memphis, Tennessee, USA. 6. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. 7. Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. 8. Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, USA. 9. Christiana Care Health System, Newark, Delaware, USA. 10. MedStar Health Research Institute, Washington, District of Columbia, USA. 11. Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. 12. Research and Analytics, Collective Health, San Francisco, California, USA; Center for Primary Care, Harvard Medical School, Boston, Massachusetts, USA; School of Public Health, Imperial College, London, United Kingdom. 13. MedStar Health Research Institute, Washington, District of Columbia, USA; Department of Medicine, Georgetown University, Washington, District of Columbia, USA.
Abstract
BACKGROUND: Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. OBJECTIVES: The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. METHODS: This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. RESULTS: Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. CONCLUSIONS: SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).
BACKGROUND: Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. OBJECTIVES: The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. METHODS: This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. RESULTS: Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. CONCLUSIONS: SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).
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