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Original research
Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care
  1. Rishi J Desai1,
  2. Elisabetta Patorno1,
  3. Muthiah Vaduganathan2,
  4. Mufaddal Mahesri1,
  5. Kristyn Chin1,
  6. Raisa Levin1,
  7. Scott D Solomon2,
  8. Sebastian Schneeweiss1
  1. 1 Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  2. 2 Heart and Vascular Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Rishi J Desai, Brigham and Women's Hospital, Boston, MA 02115, USA; rdesai{at}bwh.harvard.edu

Abstract

Objective To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF).

Methods We conducted a cohort study using US Medicare fee-for-service claims data (2014–2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects.

Results 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (−1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI.

Conclusion ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

  • heart failure

Data availability statement

Data may be obtained from a third party and are not publicly available. Patient-level data are not available for sharing due to restrictions imposed under data use agreement by the Centers for Medicare and Medicaid Services. All aggregate-level data are presented in the manuscript and supplemental content. Additional information is available from the corresponding author at rdesai@bwh.harvard.edu.

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Data availability statement

Data may be obtained from a third party and are not publicly available. Patient-level data are not available for sharing due to restrictions imposed under data use agreement by the Centers for Medicare and Medicaid Services. All aggregate-level data are presented in the manuscript and supplemental content. Additional information is available from the corresponding author at rdesai@bwh.harvard.edu.

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Footnotes

  • Twitter @Rishidesai11

  • Contributors Planning: RJD, EP, SS. Conduct: RJD, RL, MM, KC. Interpretation: all authors. Writing: all authors. RJD takes the responsibility for the overall content as guarantor of this article.

  • Funding This study was funded by internal sources of the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School.

  • Competing interests RJD reports serving as principal investigator on research grants to Brigham and Women’s Hospital from Vertex, Novartis and Bayer. EP was supported by a career development grant (K08AG055670) from the National Institute on Aging. She is investigator of an investigator-initiated grant to the Brigham and Women’s Hospital from Boehringer Ingelheim, not related to the topic of the submitted work. MV is supported by a KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), receives research grant support from Amgen, serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, Cytokinetics and Relypsa, and serves on the clinical endpoints committees of studies sponsored by Galmed, Novartis and the NIH. SDS has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Celladon, Gilead, GlaxoSmithKline, Ionis Pharmaceuticals, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur and Theracos, and has consulted for Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Corvia, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Pfizer, Takeda and Theracos. SS is co-principal investigator of investigator-initiated grants to the Brigham and Women’s Hospital from Boehringer Ingelheim, unrelated to the topic of this study. He is a consultant to Aetion, a software manufacturer of which he owns equity. His interests were declared, reviewed and approved by the Brigham and Women’s Hospital and Partners HealthCare System in accordance with their institutional compliance policies.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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