Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease


Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

Publication DOI: https://doi.org/10.1186/s12933-021-01343-1
Divisions: College of Health & Life Sciences > Aston Medical School
Funding Information: The study was funded by Ministero dell’Università e della Ricerca, PRIN 2007. Dr. Raffaele Galiero, Dr. Pia Clara Pafundi and Dr. Vittorio Simeon were supported by the Programma VALERE, University of Campania “Luigi Vanvitelli”.
Additional Information: © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Funding Information: The study was funded by Ministero dell’Università e della Ricerca, PRIN 2007.
Uncontrolled Keywords: CV risk factors,Diabetic nephropathy,Intensified treatment,MACE,Multifactorial intervention,Very high CV risk,Internal Medicine,Endocrinology, Diabetes and Metabolism,Cardiology and Cardiovascular Medicine
Publication ISSN: 1475-2840
Last Modified: 14 May 2024 16:23
Date Deposited: 07 Dec 2021 15:34
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://cardiab ... 933-021-01343-1 (Publisher URL)
PURE Output Type: Article
Published Date: 2021-07-16
Accepted Date: 2021-07-09
Authors: Sasso, F. C.
Pafundi, Pia Clara
Simeon, Vittorio
De Nicola, L.
Chiodini, Paolo
Galiero, Raffaele
Rinaldi, Luca
Nevola, Riccardo
Salvatore, Teresa
Sardu, Celestino
Marfella, Raffaele
Adinolfi, Luigi Elio
Minutolo, R.
Amelia, U.
Acierno, C.
Calatola, P.
Carbonara, O.
Caturano, A.
Conte, G.
Corigliano, G.
Corigliano, M.
D’Urso, R.
De Matteo, A.
De Nicola, L.
De Rosa, N.
Del Vecchio, E.
Di Giovanni, G.
Gatti, A.
Gentile, S.
Gesuè, L.
Improta, L.
Lampitella, A.
Lampitella, A.
Lanzilli, A.
Lascar, N. (ORCID Profile 0000-0001-9997-366X)
Masi, S.
Mattei, P.
Mastrilli, V.
Memoli, P.
Minutolo, R.
Nasti, R.
Pagano, A.
Pentangelo, M.
Pisa, E.
Rossi, E.
Sasso, F. C.
Sorrentino, S.
Torella, R.
Troise, R.
Trucillo, P.
, NID-2 Study Group Investigators



Version: Published Version

License: Creative Commons Attribution

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