Author + information
- Received June 17, 2019
- Revision received August 20, 2019
- Accepted August 26, 2019
- Published online November 25, 2019.
- Bharathi Upadhya, MDa,
- Laura C. Lovato, PhDb,
- Michael Rocco, MDc,
- Cora E. Lewis, MDd,
- Suzanne Oparil, MDe,
- William C. Cushman, MDf,
- John B. Kostis, MDg,
- Carlos J. Rodriguez, MDa,
- Monique E. Cho, MDh,
- Loretta W. Cloudb,
- Anjay Rastogi, MDi,
- Clive Rosendorff, MD, PhDj,
- Dalane W. Kitzman, MDk,∗ (, )
- for the SPRINT Research Group
- aCardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- bBiostatistics and Data Science, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- cNephrology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- dDepartment of Epidemiology, Department of Medicine, University of Alabama, Birmingham, Alabama
- eDivision of Cardiovascular Disease, Department of Medicine, University of Alabama, Birmingham, Alabama
- fPreventive Medicine Section, Veterans Affairs Medical Center, Memphis, Tennessee
- gCardiovascular Institute, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
- hDivision of Hypertension and Nephrology, University of Utah, Salt Lake City, Utah
- iDivision of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
- jMount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York
- kJames J. Peters Veterans Affairs Medical Center, Bronx, New York
- ↵∗Address for correspondence:
Dr. Dalane W. Kitzman, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045.
Objectives This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study.
Background SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications.
Methods Detailed use of medication data prospectively collected throughout the trial were examined.
Results ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83).
Conclusions No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).
Supported by U.S. National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases/National Institute on Aging/National Institute of Neurological Disorders and Stroke contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN268200900049C, and Inter-Agency Agreement A-HL-13-002-001. Additional support was provided by Department of Veterans Affairs; National Center for Advancing Translational Sciences Clinical and Translational Science Awards UL1TR000439, UL1RR025755, UL1RR024134, UL1TR000003, UL1RR025771, UL1TR000093, UL1RR025752, UL1TR000073, UL1TR001064, UL1TR000050, UL1TR000005, 9U54TR000017-06, UL1TR000105-05, UL1TR000445, UL1TR000075, UL1TR000002, UL1TR000064, and UL1TR000433; National Institute of General Medical Sciences Centers of Biomedical Research Excellence award P30GM103337; NIH grants R01AG18915, R01HL107257, P30AG021332, U24AG05964, and R01AG045551; and by the Kermit G. Phillips II Chair, Wake Forest School of Medicine, Winston-Salem, North Carolina. Dr. Rocco is a consultant for Abbvie, George Clinical, Beacon Bioscience, Baxter, Bayer, Boehringer Ingelheim, and GlaxoSmithKline. Dr. Lewis has received research support from NIH. Dr. Oparil received personal fees from Forest Laboratories Inc.; grants, personal fees, and nonfinancial support from Medtronic; personal fees from Amgen (Onyx is subsidiary); grants and personal fees from AstraZeneca and Bayer Healthcare Pharmaceuticals Inc.; personal fees from Boehringer Ingelheim and GlaxoSmithKline; grants from Merck and Co.; and serves as cochair for the Eighth Joint National Committee. Dr. Kitzman is a consultant for Abbvie, Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, CinRx, Novartis, and Actavis; has received research support from Novartis, Bayer, and AstraZeneca; and holds stock ownership in Gilead Sciences. Dr. Upadhya has financial arrangements with Novartis and Corvia. Dr. Kostis is a consultant for Abbott, Abbvie, and Sanofi; and has received research support from Sanofi, AstraZeneca, Hamilton Health Sciences, and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 17, 2019.
- Revision received August 20, 2019.
- Accepted August 26, 2019.
- 2019 American College of Cardiology Foundation
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