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Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial

Abstract

Background

Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making.

Objectives

To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days

Design

Post hoc analysis of the Systolic Blood Pressure Intervention Trial

Participants

A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130–180 mmHg and elevated cardiovascular risk

Interventions

Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg)

Main Measures

Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years

Key Results

The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, −15.0 [−56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, −22.7 [−51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, −14.8 [−35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event–free days than the standard treatment group (difference, −28.5 [−40.3, −16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, −15.5 [−46.6, 15.7] days) and self-rated health (excellent: difference, −12.9 [−45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001).

Conclusions

Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated.

Trial Registration

ClinicalTrials.gov Registration: NCT01206062

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Acknowledgements

We thank the patients who participated in the Systolic Blood Pressure Intervention Trial (SPRINT) for their important contributions. For a full list of contributors to SPRINT, please visit www.sprinttrial.org.

Dr. Dae Hyun Kim affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained. Dr. Curtis Tatsuoka had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

The SPRINT is funded with federal funds from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C, and Inter-Agency Agreement Number A-HL-13-002-001. It was supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. We also acknowledge the support from the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences (NCATS): CWRU: UL1TR000439, OSU: UL1RR025755, U Penn: UL1RR024134& UL1TR000003, Boston: UL1RR025771, Stanford: UL1TR000093, Tufts: UL1RR025752, UL1TR000073 & UL1TR001064, University of Illinois: UL1TR000050, University of Pittsburgh: UL1TR000005, UT Southwestern: 9U54TR000017-06, University of Utah: UL1TR000105-05, Vanderbilt University: UL1 TR000445, George Washington University: UL1TR000075, University of CA, Davis: UL1 TR000002, University of Florida: UL1 TR000064, University of Michigan: UL1TR000433, Tulane University: P30GM103337 COBRE Award NIGMS, Wake Forest University: UL1TR001420. This analysis was also supported by grant R21AG060227 from NIA. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of manuscript writing and revision were carried out by the coauthors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of Veterans Affairs, or the United States Government. For a full list of contributors to SPRINT, please see the supplementary acknowledgement list: https://www.sprinttrial.org/public/dspScience.cfm.

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Authors

Contributions

Conception and design: D.H. Kim, M. Odden, L.J. Wei

Analysis and interpretation of the data: All authors

Drafting of the article: D.H. Kim

Critical revision of the article for important intellectual content: All authors

Final approval of the article: All authors

Provision of study materials or patients: J.T. Wright

Statistical expertise: C. Tatsuoka, Z. Chen, L.J. Wei

Obtaining of funding: D.H. Kim

Administrative, technical, or logistic support: D.H. Kim

Corresponding author

Correspondence to Dae Hyun Kim MD, MPH, ScD.

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Kim, D.H., Tatsuoka, C., Chen, Z. et al. Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial. J GEN INTERN MED (2022). https://doi.org/10.1007/s11606-022-07753-5

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  • DOI: https://doi.org/10.1007/s11606-022-07753-5