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      Cardiovascular Effectiveness of Sodium‐Glucose Cotransporter 2 Inhibitors and Glucagon‐Like Peptide‐1 Receptor Agonists in Older Patients in Routine Clinical Care With or Without History of Atherosclerotic Cardiovascular Diseases or Heart Failure

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          Abstract

          Background

          Randomized trials demonstrate the cardioprotective effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). We evaluated their relative cardiovascular effectiveness in routine care populations with a broad spectrum of atherosclerotic cardiovascular diseases (CVDs) or heart failure (HF).

          Methods and Results

          We identified Medicare beneficiaries from 2013 to 2017, aged >65 years, initiating SGLT2i (n=24 747) or GLP‐1RA (n=22 596) after a 1‐year baseline. On the basis of diagnoses during baseline, we classified patients into: (1) no HF or CVD, (2) HF but no CVD, (3) no HF but CVD, and (4) both HF and CVD. We identified hospitalized HF and atherosclerotic CVD outcomes from drug initiation until treatment changes, death, or disenrollment. We estimated propensity score–weighted 2‐year risk ratios (RRs) and risk differences, accounting for measured confounding, informative censoring, and competing risk. In patients with no CVD or HF, SGLT2i reduced the hospitalized HF risk compared with GLP‐1RA (propensity score–weighted RR, 0.65; 95% CI, 0.43–0.96). The association was strongest in those who had HF but no CVD (RR, 0.48; 95% CI, 0.25–0.85). The combined myocardial infarction, stroke, and mortality outcome risk was slightly higher for SGLT2i compared with GLP‐1RA in those without CVD or HF (RR, 1.31; 95% CI, 1.09–1.56). The association was favorable toward SGLT2i in subgroups with a history of HF.

          Conclusions

          SGLT2i reduced the cardiovascular risk versus GLP‐1RA in patients with a history of HF but no CVD. Atherosclerotic CVD events were less frequent with GLP‐1RA in those without prior CVD or HF.

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          Most cited references50

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies

            The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses.
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              Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

              In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.
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                Author and article information

                Contributors
                sturmer@unc.edu
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                08 February 2022
                15 February 2022
                : 11
                : 4 ( doiID: 10.1002/jah3.v11.4 )
                : e022376
                Affiliations
                [ 1 ] Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Boston MA
                [ 2 ] University of North Carolina at Chapel Hill School of Medicine Chapel Hill NC
                [ 3 ] Department of Epidemiology University of North Carolina at Chapel Hill Gillings School of Global Public Health Chapel Hill NC
                Author notes
                [*] [* ] Correspondence to: Til Stürmer, MD, PhD, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599‐7435. E‐mail: sturmer@ 123456unc.edu

                Author information
                https://orcid.org/0000-0003-4742-8306
                https://orcid.org/0000-0002-9723-3876
                https://orcid.org/0000-0002-4466-4760
                https://orcid.org/0000-0002-1741-335X
                https://orcid.org/0000-0002-9204-7177
                Article
                JAH37094
                10.1161/JAHA.121.022376
                9245812
                35132865
                ae8be518-679e-4181-b54d-fdfca67f3c3a
                © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 21 June 2021
                : 22 November 2021
                Page count
                Figures: 6, Tables: 1, Pages: 18, Words: 11148
                Funding
                Funded by: UNC Gillings School of Global Public Health
                Funded by: Cecil G. Sheps Center for Health Services Research, UNC
                Funded by: CER Strategic Initiative of UNC’s Clinical and Translational Science Award
                Award ID: UL1TR002489
                Funded by: UNC School of Medicine , doi 10.13039/100011082;
                Categories
                Original Research
                Original Research
                Epidemiology
                Custom metadata
                2.0
                February 15, 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:28.06.2022

                Cardiovascular Medicine
                glucagon‐like peptide‐1 receptor,heart failure,myocardial infarction,sodium‐glucose transporter 2 inhibitors,type 2 diabetes,diabetes, type 2,cerebrovascular disease/stroke,coronary artery disease

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