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

Cardiovasc Diabetol. 2021 Jul 16;20(1):145. doi: 10.1186/s12933-021-01343-1.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / diagnosis
  • Albuminuria / mortality
  • Albuminuria / therapy*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / therapy*
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / mortality
  • Diabetic Retinopathy / therapy*
  • Diet, Sodium-Restricted
  • Exercise
  • Female
  • Healthy Lifestyle*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Italy
  • Male
  • Middle Aged
  • Risk Assessment
  • Risk Factors
  • Risk Reduction Behavior*
  • Time Factors
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Hypoglycemic Agents
  • Hypolipidemic Agents

Associated data

  • ClinicalTrials.gov/NCT00535925