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

F. C. Sasso; Pia Clara Pafundi; Vittorio Simeon; L. De Nicola; Paolo Chiodini; Raffaele Galiero; Luca Rinaldi; Riccardo Nevola; Teresa Salvatore; Celestino Sardu; Raffaele Marfella; Luigi Elio Adinolfi; R. Minutolo; U. Amelia; C. Acierno; P. Calatola; O. Carbonara; A. Caturano; G. Conte; G. Corigliano; M. Corigliano; R. D’Urso; A. De Matteo; L. De Nicola; N. De Rosa; E. Del Vecchio; G. Di Giovanni; A. Gatti; S. Gentile; L. Gesuè; L. Improta; A. Lampitella; A. Lampitella; A. Lanzilli; N. Lascar; S. Masi; P. Mattei; V. Mastrilli; P. Memoli; R. Minutolo; R. Nasti; A. Pagano; M. Pentangelo; E. Pisa; E. Rossi; F. C. Sasso; S. Sorrentino; R. Torella; R. Troise; P. Trucillo

doi:10.1186/s12933-021-01343-1

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

F. C. Sasso, Pia Clara Pafundi, Vittorio Simeon, L. De Nicola, Paolo Chiodini, Raffaele Galiero, Luca Rinaldi, Riccardo Nevola, Teresa Salvatore, Celestino Sardu, Raffaele Marfella, Luigi Elio Adinolfi, R. Minutolo, U. Amelia, C. Acierno, P. Calatola, O. Carbonara, A. Caturano, G. Conte, G. CoriglianoM. Corigliano, R. D’Urso, A. De Matteo, L. De Nicola, N. De Rosa, E. Del Vecchio, G. Di Giovanni, A. Gatti, S. Gentile, L. Gesuè, L. Improta, A. Lampitella, A. Lampitella, A. Lanzilli, N. Lascar, S. Masi, P. Mattei, V. Mastrilli, P. Memoli, R. Minutolo, R. Nasti, A. Pagano, M. Pentangelo, E. Pisa, E. Rossi, F. C. Sasso, S. Sorrentino, R. Torella, R. Troise, P. Trucillo,

Aston Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	English
Article number	145
Journal	Cardiovascular Diabetology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12933-021-01343-1
Publication status	Published - 16 Jul 2021

Bibliographical note

© 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.

Keywords

CV risk factors
Diabetic nephropathy
Intensified treatment
MACE
Multifactorial intervention
Very high CV risk

Access to Document

10.1186/s12933-021-01343-1Licence: CC BY 3.0

Efficacy and durability of multifactorial intervention on mortality and MACEs
© 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. 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.
Final published version, 1.1 MBLicence: CC BY 3.0

Cite this

Sasso, F. C., Pafundi, P. C., Simeon, V., De Nicola, L., Chiodini, P., Galiero, R., Rinaldi, L., Nevola, R., Salvatore, T., Sardu, C., Marfella, R., Adinolfi, L. E., Minutolo, R., Amelia, U., Acierno, C., Calatola, P., Carbonara, O., Caturano, A., Conte, G. (2021). Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease. Cardiovascular Diabetology, 20(1), Article 145. https://doi.org/10.1186/s12933-021-01343-1

@article{5abef786df1f4a838461e2349ba8adb1,

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

abstract = "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",

keywords = "CV risk factors, Diabetic nephropathy, Intensified treatment, MACE, Multifactorial intervention, Very high CV risk",

author = "Sasso, {F. C.} and Pafundi, {Pia Clara} and Vittorio Simeon and {De Nicola}, L. and Paolo Chiodini and Raffaele Galiero and Luca Rinaldi and Riccardo Nevola and Teresa Salvatore and Celestino Sardu and Raffaele Marfella and Adinolfi, {Luigi Elio} and R. Minutolo and U. Amelia and C. Acierno and P. Calatola and O. Carbonara and A. Caturano and G. Conte and G. Corigliano and M. Corigliano and R. D{\textquoteright}Urso and {De Matteo}, A. and {De Nicola}, L. and {De Rosa}, N. and {Del Vecchio}, E. and {Di Giovanni}, G. and A. Gatti and S. Gentile and L. Gesu{\`e} and L. Improta and A. Lampitella and A. Lampitella and A. Lanzilli and N. Lascar and S. Masi and P. Mattei and V. Mastrilli and P. Memoli and R. Minutolo and R. Nasti and A. Pagano and M. Pentangelo and E. Pisa and E. Rossi and Sasso, {F. C.} and S. Sorrentino and R. Torella and R. Troise and P. Trucillo",

note = "{\textcopyright} 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{\textquoteright}s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}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{\textquoteright}Universit{\`a} e della Ricerca, PRIN 2007. ",

year = "2021",

month = jul,

day = "16",

doi = "10.1186/s12933-021-01343-1",

language = "English",

volume = "20",

journal = "Cardiovascular Diabetology",

issn = "1475-2840",

publisher = "BioMed Central",

number = "1",

}

Sasso, FC, Pafundi, PC, Simeon, V, De Nicola, L, Chiodini, P, Galiero, R, Rinaldi, L, Nevola, R, Salvatore, T, Sardu, C, Marfella, R, Adinolfi, LE, 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, Masi, S, Mattei, P, Mastrilli, V, Memoli, P, Minutolo, R, Nasti, R, Pagano, A, Pentangelo, M, Pisa, E, Rossi, E, Sasso, FC, Sorrentino, S, Torella, R, Troise, R, Trucillo, P 2021, 'Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease', Cardiovascular Diabetology, vol. 20, no. 1, 145. https://doi.org/10.1186/s12933-021-01343-1

TY - JOUR

T1 - Efficacy and durability of multifactorial intervention on mortality and MACEs

T2 - a randomized clinical trial in type-2 diabetic kidney disease

AU - Sasso, F. C.

AU - Pafundi, Pia Clara

AU - Simeon, Vittorio

AU - De Nicola, L.

AU - Chiodini, Paolo

AU - Galiero, Raffaele

AU - Rinaldi, Luca

AU - Nevola, Riccardo

AU - Salvatore, Teresa

AU - Sardu, Celestino

AU - Marfella, Raffaele

AU - Adinolfi, Luigi Elio

AU - Minutolo, R.

AU - Amelia, U.

AU - Acierno, C.

AU - Calatola, P.

AU - Carbonara, O.

AU - Caturano, A.

AU - Conte, G.

AU - Corigliano, G.

AU - Corigliano, M.

AU - D’Urso, R.

AU - De Matteo, A.

AU - De Nicola, L.

AU - De Rosa, N.

AU - Del Vecchio, E.

AU - Di Giovanni, G.

AU - Gatti, A.

AU - Gentile, S.

AU - Gesuè, L.

AU - Improta, L.

AU - Lampitella, A.

AU - Lanzilli, A.

AU - Lascar, N.

AU - Masi, S.

AU - Mattei, P.

AU - Mastrilli, V.

AU - Memoli, P.

AU - Minutolo, R.

AU - Nasti, R.

AU - Pagano, A.

AU - Pentangelo, M.

AU - Pisa, E.

AU - Rossi, E.

AU - Sasso, F. C.

AU - Sorrentino, S.

AU - Torella, R.

AU - Troise, R.

AU - Trucillo, P.

N1 - © 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.

PY - 2021/7/16

Y1 - 2021/7/16

N2 - 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

AB - 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

KW - CV risk factors

KW - Diabetic nephropathy

KW - Intensified treatment

KW - MACE

KW - Multifactorial intervention

KW - Very high CV risk

UR - http://www.scopus.com/inward/record.url?scp=85110718524&partnerID=8YFLogxK

UR - https://cardiab.biomedcentral.com/articles/10.1186/s12933-021-01343-1

U2 - 10.1186/s12933-021-01343-1

DO - 10.1186/s12933-021-01343-1

M3 - Article

C2 - 34271948

AN - SCOPUS:85110718524

SN - 1475-2840

VL - 20

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

IS - 1

M1 - 145

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this