Reply to: Intensive Blood Pressure Targets in Geriatrics: Individualized Decision‐Making and Unresolved Risks

We thank Dr. Akcay for his thoughtful letter 1 on our article “Individualized Net Benefit of Intensive Blood Pressure Lowering Among Community-Dwelling Older Adults in SPRINT” 2. Dr. Akcay's comments about the generalizability of SPRINT to older adults, the differences between frailty assessment in research versus clinical practice, and considering the long-term benefits and harms of hypertension treatment are all important. We share his commitment to optimizing blood pressure (BP) management for older adults through an individualized, shared decision-making approach. Before responding to the letter's specific concerns, we must point out the large differences between the community-dwelling, noninstitutionalized, ambulatory older adults in SPRINT versus the frailest, most clinically complex older adults with limited-life expectancy for whom Dr. Akcay suggests a conservative BP target. Even the subset of older SPRINT participants who were described as frail or having polypharmacy were able to consent to joining SPRINT and adhere to its protocolized study visits. Conflating SPRINT-eligible older adults with the population described in Dr. Akcay's letter impedes the decision to treat to an intensive BP target for our older patients who would clearly benefit. The letter raises concerns about our analysis overweighting the importance of disease-related outcomes (e.g., cardiovascular disease CVD events and cognitive impairment) compared with BP treatment-related harms (e.g., emergency department visits or hospitalizations for acute kidney injury AKI and syncope). The treatment-related harms in SPRINT were generally mild and transient, whereas dementia and CVD events such as heart failure and stroke often have significant and long-lasting detrimental impacts on quality of life. Moreover, in our manuscript, we demonstrate that individuals would have had to prioritize the avoidance of BP treatment-related harms even more than CVD events and cognitive impairment for the benefit-harm trade-off to favor standard BP treatment over intensive BP treatment. The letter also questions whether syncope, fractures, and hospitalizations were directly captured in SPRINT; these outcomes as well as kidney-related and hemodynamic-related adverse events were pre-specified events of interest, monitored using a structured protocol, and rigorously adjudicated. Finally, the letter notes that “observational evidence provides a contrasting perspective” linking lower BP to higher mortality in older adults, but these observational data are likely limited by reverse causation (i.e., lower BP in older adults may be a marker for less robust health) 3. SPRINT and other recent BP target trials demonstrate a significant mortality benefit with targeting an intensive BP goal in older adults 4, 5. These data highlight the importance of using evidence from randomized trials to guide BP target decisions, which indeed is specifically why SPRINT was designed and conducted. We believe the concerns raised by Dr. Akcay highlight a broader challenge in clinical practice; we often only see the harms from treatments that we prescribe, but not the counterfactual events prevented, which naturally biases clinicians towards less aggressive treatment. Only when a trial is conducted and both benefits and harms are carefully adjudicated can one discern the trade-offs. While older patients may be at high risk of AKI and syncope from more intensive BP treatment, they are also at high risk of CVD, cognitive impairment, and death when BP is left higher. Guiding BP target decisions based primarily on the treatment-related harms without full consideration of the benefits leads to a treatment-risk paradox for older patients: those who are at highest risk of hypertension-related outcomes are less likely to be treated to a lower BP goal 6. Our net benefit method explicitly captures the benefit-harm trade-offs for each individual using predicted risks and patient preferences. We believe that this approach to BP target recommendations may help nudge clinicians to overcome therapeutic inertia when treating hypertension in older adults by reminding us that the benefits of targeting an intensive BP goal often substantially outweigh the harms. We hope similar net benefit frameworks are investigated for other treatment decisions involving complex trade-offs for older adults, including anticoagulation, cancer therapy, and higher risk surgeries. Preparation on manuscript: M.S.J., S.B.A., J.H.I., and M.G.S. This study was supported by the NIDDK (R01DK098234 for J.H.I. and M.G.S., and K24DK110427 for J.H.I.); the NHLBI (K23HL173670 for S.B.A.); the American Heart Association (14EIA18560026 for J.H.I. and career development award 936281 for S.B.A.); the American Society of Nephrology, KidneyCure Ben J. Lipps Research Grant for M.S.J.; and the National Center for Advancing Translational Sciences, National Institutes of Health (through grant number UL1TR001860 and linked award KL2TR001859 for S.B.A.). M.G.S. has received consulting income from Cricket Health Inc.; has served on advisory panels for Boehringer Ingelheim, AstraZeneca, and Bayer; and has received research support from Bayer. J.H.I. holds an investigator-initiated research grant from Baxter International Inc. is also principal investigator of an investigator initiated trial supported by Breakthrough T1D; has received travel support from KGIGO and ASNA; serves as a member of a data safety monitoring board for Sanifit Therapeutics; is a member of the scientific advisory board for Alpha Young; has served on advisory boards as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Otsuka, and Ardelyx; and has received donated drug and placebo for a study with Genetech (but no financial support). The other authors declare no conflicts of interest. This publication is linked to a related reply by Omer Faruk Akcay To view this article, visit https://doi.org/10.1111/jgs.70261.