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
Cardiovascular Diabetology